This study will evaluate the colorectal cancer screening continuum — tests, screening quality, follow-up care, and health outcomes — over a 20-year time period that covers before, during, and after implementation of an organized colorectal cancer screening at KPNC and…
This study will include 1500 patients with advanced lung, pancreatic, or colorectal cancer at high risk of cachexia for detailed measurement via biospecimen collection, remote monitoring, questionnaire, and medical record review. The aims are to: identify distinct cachexia subtypes with…
Programmatic colorectal cancer (CRC) screening increases uptake, but the design and resources utilized for such models are not well known. We characterized program components and participation at each step in a large program that used mailed fecal immunochemical testing (FIT)…
The longitudinal risk of colorectal cancer (CRC) associated with subtypes of serrated polyps (SPs) remains incompletely understood. This community-based, case-control study included 317 178 Kaiser Permanente Northern California members who underwent their first colonoscopy during 2006-2016. Nested within this population,…
Three national guideline groups now recommend that all adults start colorectal cancer (CRC) screening at age 45. Before 2018, some guideline groups only recommended African Americans begin CRC screening at age 45. There is currently no empirical evidence of the…
Optimization of Diagnosis and Surveillance of Colonic Sessile Serrated Adenomas by Pathologists and Gastroenterologists at KPNC.
Patients with mismatch repair (MMR) deficient colorectal cancer (CRC) without detectable germline pathogenic variants (PVs) or likely pathogenic variants (LPVs) in MMR genes are often labeled as Lynch-like syndrome (LLS). We sought to evaluate the efficacy of paired tumor and…
An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental…
The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention…
There is an emerging viewpoint that change in body weight is not sufficiently sensitive to promptly identify clinically meaningful change in body composition, such as skeletal muscle depletion. We aimed to determine whether body weight stability is associated with skeletal…
The primary objectives of this study are to determine the sensitivity and specificity of Freenome's test for colorectal adenocarcinoma, using screening CS with histopathology as the reference method.
Colonoscopy surveillance is recommended for patients at increased risk of colorectal cancer (CRC) following adenoma removal. Low-, intermediate-, and high-risk groups are defined by baseline adenoma characteristics. We previously examined intermediate-risk patients from hospital data and identified a higher-risk subgroup…
Rising trends in the incidence and mortality of early-onset colorectal cancer (CRC) in those who are younger than 50 years have been well established. These trends have spurred intense investigation focused on elucidating the epidemiology and characteristics of early-onset CRC,…
Susceptibility genes and the underlying mechanisms for the majority of risk loci identified by genome-wide association studies (GWAS) for colorectal cancer (CRC) risk remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify putative susceptibility genes. Gene-expression prediction…
Lynch syndrome (LS) is the most common type of hereditary colorectal cancer (CRC) syndrome caused by pathogenic variants in mismatch repair (MMR) genes.1 Current multisociety guidelines recommend screening all CRC tumors for LS.2,3 The most widely adopted screening method is…
Metalworking fluids (MWFs) are a class of complex mixtures of chemicals and oils, including several known carcinogens that may pose a cancer hazard to millions of workers. Reports on the relation between MWFs and incident colon cancer have been mixed.…
Body mass index (BMI) is a complex phenotype that may interact with genetic variants to influence colorectal cancer risk. We tested multiplicative statistical interactions between BMI (per 5 kg/m2) and approximately 2.7 million single nucleotide polymorphisms with colorectal cancer risk among…
High numbers of lymphocytes in tumor tissue, including T regulatory cells (Treg), have been associated with better colorectal cancer survival. Tregs, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and therefore variants in genes related to…
Primary care provider's (PCP) perceptions of colorectal cancer screening test effectiveness and their recommendations for testing intervals influence patient screening uptake. Few large studies have examined providers' perceptions and recommendations, including their alignment with evidence suggesting comparable test effectiveness and…
Some guidelines recommend starting colorectal cancer (CRC) screening before age 50 years for African Americans, but there are few data on screening uptake and yield in this population. We performed a prospective study of fecal immunochemical test (FIT) screening among…
The goal of this project is to evaluate the impact of the COVID pandemic on colorectal cancer screening and surveillance activities, and the impact on outcomes such as colorectal cancer incidence and stage.
Protective associations of fruits, vegetables, and fiber intake with colorectal cancer risk have been shown in many, but not all epidemiologic studies. One possible reason for study heterogeneity is that dietary factors may have distinct effects by colorectal cancer molecular…
Given the risks of postoperative morbidity and its consequent economic burden and impairment to patients undergoing colon resection, evaluating risk factors associated with complications will allow risk stratification and the targeting of supportive interventions. Evaluation of muscle characteristics is an…
Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer…
Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are…
Postmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location. We…
Serrated polyp (SPs) are precursors to 20% to 30% of cases of colorectal tumors, but patients' long-term risk after removal of SPs is poorly understood. We investigated the risk of colorectal cancer (CRC) in individuals with a history of SPs.…
Key variables recorded as text in colonoscopy and pathology reports have been extracted using natural language processing (NLP) tools that were not easily adaptable to new settings. We aimed to develop a reliable NLP tool with broad adaptability. During 1996-2016,…
We are using post-polypectomy surveillance, an increasingly common indication for colonoscopy in clinical practice at TPMG and across the United States, as a model for how we might risk-stratify patients for care. Patients and physicians desire more precise estimates of…
This is a non-inferiority trial design comparing colorectal cancer incidence in trial participants with 1-2 non-advanced adenomas randomized to recommendation for a 5- and 10-year surveillance colonoscopy exam vs. a 10-year surveillance colonoscopy exam.
A Kaiser Permanente interregional cancer statistics report will be developed to include incidence and 5-year relative survival rates for breast, colorectal, and lung cancer. The development of new mortality measures will be explored, along with improved routine capture and reporting…
Body mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify…
We evaluated associations between perceived social support, social integration, living alone, and colorectal cancer (CRC) outcomes in postmenopausal women. The study included 1431 women from the Women's Health Initiative who were diagnosed from 1993 through 2017 with stage I through…
Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk…
Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine…
The quantity and distribution of adipose tissue may be prognostic measures of mortality in colorectal cancer patients, and such associations may vary by patient sex. This cohort included 3262 stage I-III colorectal cancer patients. Visceral and subcutaneous adipose tissues were…
Dietary factors may influence colorectal cancer (CRC) survival through effects on inflammation. We examined the association between post-CRC diagnosis inflammatory potential of diet and all-cause and cancer-specific mortality in the Women's Health Initiative. The study included 463 postmenopausal women who…
Among colon cancer patients participating in a resistance training intervention during chemotherapy, this study will examine whether a new method to evaluate skeletal muscle mass (d3-creatine dilution) is associated with the key cancer outcomes of strength and physical function, chemotherapy…
The long-term risks of colorectal cancer (CRC) and CRC-related death following adenoma removal are uncertain. Data are needed to inform evidence-based surveillance guidelines, which vary in follow-up recommendations for some polyp types. Using data from a large, community-based integrated health…
Cancer screening is a complex process encompassing risk assessment, the initial screening examination, diagnostic evaluation, and treatment of cancer precursors or early cancers. Metrics that enable comparisons across different screening targets are needed. We present population-based screening metrics for breast,…
Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of…
Interindividual differences in DNA repair systems may play a role in modulating the individual risk of developing colorectal cancer. To better ascertain the role of DNA repair gene polymorphisms on colon and rectal cancer risk individually, we evaluated 15,419 single…
Quantitative fecal immunochemical tests (FITs) for hemoglobin are commonly used for colorectal cancer (CRC) screening. We aimed to quantify the change in CRC and advanced adenoma detection and number of positive test results at different positivity thresholds and by sex…
Rates of surgery for nonmalignant colorectal polyps are increasing in the United States despite evidence that most polyps can be managed endoscopically. We aimed to determine nationally representative estimates and to identify predictors of in-hospital mortality and morbidity after surgery…
Recent 15-year updates of sigmoidoscopy screening trials provide new evidence on the effectiveness of colorectal cancer screening. Prompted by the new evidence, we asked: "Does colorectal cancer screening make an important difference to health outcomes in individuals initiating screening at…
Despite the importance of characterizing colonoscopy indication for quality monitoring and cancer screening program evaluation, there is no standard approach to documenting colonoscopy indication in medical records. We applied two algorithms in three health care systems to assign colonoscopy indication…
Guidelines recommend screening all patients with newly diagnosed colorectal cancer (CRC) for Lynch syndrome (LS). However, the efficiency of universal LS screening in elderly populations has not been well studied. To compare the performance of age-restricted and universal LS screening…
As people with HIV (PWH) live longer, age-appropriate colorectal cancer (CRC) screening is increasingly important. Limited data exist on CRC screening and outcomes comparing PWH and persons without HIV. Large integrated health care system. This study included PWH and demographically…
Our objective was to describe differences in treatment patterns and survival between early-onset ( 12 lymph nodes examined (OR 1.60, CI 1.37-1.87), to receive systemic therapy (chemotherapy or immunotherapy) within 6 months of diagnosis (OR 2.84, CI 2.40-3.37), and to have a…
Patients with colorectal cancer (CRC) are up to 4-fold more likely than individuals without a history of cancer to develop cardiovascular disease. Clinical care guidelines recommend that physicians counsel patients with CRC regarding the association between obesity (defined using body…
Few studies have examined outcomes of high-resolution anoscopy (HRA)-based screening for people with HIV infection (PWH), a population at increased risk for anal cancer. Large integrated health care system. Cohort study of 13,552 people with HIV infection, comparing incidences of…
Chronic inflammation is a risk factor for colorectal cancer (CRC). Circulating C-reactive protein (CRP) is also moderately associated with CRC risk. However, observational studies are susceptible to unmeasured confounding or reverse causality. Using genetic risk variants as instrumental variables, we…
The purpose of this study was to test the hypothesis that patients with Medicaid insurance or Medicaid-like coverage would have longer times to follow-up and be less likely to complete colonoscopy compared with patients with commercial insurance within the same…
Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and…
As part of a K training award, and within our overall colorectal cancer research program, this award will support additional analyses regarding the identification of persons at high hereditary risk for colorectal cancer (e.g., Lynch syndrome) and their use of…
This project builds on a previous Community Benefit grant award to examine changes in cervical and colorectal cancer screening as a result of the implementation of the Patient Protection and Affordable Care Act. It will examine impacts on colorectal cancer incidence and mortality. This will be…
Sarcopenia and low skeletal muscle radiodensity (SMD) have been associated with adverse outcomes in patients with colorectal cancer (CRC); however, factors contributing to these 2 muscle abnormalities are unclear. The aim of this study was to investigate the association of…
I-scan is an electronic chromoendoscopy technology that improves resolution of epithelial and mucosal surfaces and vessels. We performed a randomized controlled trial to compare detection of adenomas by i-scan vs standard high-definition white-light (HDWL) colonoscopy. From February 1 through December…
The effectiveness of fecal immunochemical test (FIT) screening for colorectal cancer depends on timely colonoscopy follow-up of positive tests, although limited data exist regarding effective system-level strategies for improving follow-up rates. Using a mixed-methods design (qualitative and quantitative), we first…
Guidelines recommend a 10-year rescreening interval after a colonoscopy with normal findings (negative colonoscopy results), but evidence supporting this recommendation is limited. To examine the long-term risks of colorectal cancer and colorectal cancer deaths after a negative colonoscopy result, in…
Liver diseases including non-alcoholic fatty liver disease (NAFLD) and ensuing alterations to the micro-environment may affect development of liver metastasis. Mirroring the rise in obesity rates, prevalence of NAFLD is increasing globally. Our objective was to examine the association between…
Colorectal cancer (CRC) causes more than 50,000 deaths each year in the United States but early detection through screening yields survival gains; those diagnosed with early stage disease have a 5-year survival greater than 90%, compared to 12% for those…
Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. We conducted a GWAS in European…
To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in…
To reduce colorectal cancer incidence and mortality, experts recommend surveillance colonoscopy 3 years after advanced adenoma removal. Little is known about adherence to that interval. We describe patterns of and factors associated with subsequent colonoscopy among persons with ?3 adenomas…
Colorectal cancer (CRC) deaths occur when patients do not receive screening or have inadequate follow-up of abnormal results or when the screening test fails. We have few data on the contribution of each to CRC-associated deaths or factors associated with these…
Screening reduces colorectal cancer deaths, but?
Postcolonoscopy colorectal cancers (PCCRCs) are defined as those detected ≤10 years after an index colonoscopy negative for cancer, but modifiable risk factors are not well established in large, community-based populations. We evaluated risk factors from the index colonoscopy for PCCRCs diagnosed…
Few population-level surveys have explored patient-centered priorities for improving colorectal cancer survivors' care. Working with patients, we designed a survey to identify care improvement and survivorship priorities. We surveyed a random sample of 4000 patients from a retrospective, population-based cohort…
The aim of this study was to test the ability of a commercially available natural language processing (NLP) tool to accurately extract examination quality-related and large polyp information from colonoscopy reports with varying report formats. Colonoscopy quality reporting often requires…
To investigate the implications of a cancer diagnosis on medication adherence for pre-existing comorbid conditions, we explored statin adherence patterns prior to and following a new diagnosis of breast, colorectal, or prostate cancer among a multi-ethnic cohort. We identified adults…
MUTYH-associated polyposis (MAP) is a hereditary cancer syndrome that is caused by biallelic pathogenic variants in the MUTYH gene and should be evaluated for in patients with an attenuated colonic polyposis phenotype. Monoallelic pathogenic variants in MUTYH are associated with…
The fecal immunochemical test (FIT) is commonly used for colorectal cancer (CRC) screening. Despite demographic variations in stool hemoglobin concentrations, few data exist regarding optimal positivity thresholds by age and sex. To identify programmatic (multitest) FIT performance characteristics and optimal…
HIV-infected individuals are at increased risk of anal cancer. Screening for anal cancer precursors using high-resolution anoscopy (HRA) may be clinically beneficial. In this study, we examined patient tolerability of this procedure. The acceptability of HRA was evaluated among HIV-infected…
Little information is available on the effectiveness of organized colorectal cancer (CRC) screening on screening uptake, incidence, and mortality in community-based populations. We contrasted screening rates, age-adjusted annual CRC incidence, and incidence-based mortality rates before (baseline year 2000) and after…
Although obesity has now been widely accepted to be an important risk factor for cancer survival, the associations between BMI and cancer mortality have not been consistently linear. Although morbid obesity has clearly been associated with worse survival, some studies…
Screening has been shown to reduce colorectal cancer incidence and mortality. However, screening has resulted in a growing cohort of patients with adenomatous polyps (adenomas), and little is known about effectively managing their post-polypectomy surveillance. With limited data available in…
As part of a “K” training award from the National Institutes of Health, and within the overall colorectal cancer research program at Kaiser Permanente Northern California, this project will support additional analyses regarding the identification of persons at high hereditary…
Colonoscopy examination does not always detect colorectal cancer (CRC)- some patients develop CRC after negative findings from an examination. When this occurs before the next recommended examination, it is called interval cancer. From a colonoscopy quality assurance perspective, that term…
Background: Some prior studies have reported reduced colorectal cancer risk among individuals using antidepressant medications, especially selective serotonin reuptake inhibitors (SSRIs). Yet most studies have not considered the potential role of depression or other confounders in their analyses.Methods: We utilized…
Co-morbidities and computerized tomography-measured muscle abnormalities are both common in cancer patients and independently adversely influence clinical outcomes. Muscle abnormalities are also evident in other diseases, such as diabetes and obesity. This study examined for the first time the association…
Low skeletal muscle quantified using computed tomography (CT) scans is associated with morbidity and mortality among cancer patients. However, existing methods to assess skeletal muscle from CT are time-consuming, expensive, and require training. Clinic-friendly tools to screen for low skeletal…
This project consists of development of electronic tools to rapidly assess body composition in colorectal cancer and breast cancer patients and present this information to clinicians. It leverages Kaiser Permanente Northern California’s electronic medical records and repository of CT images,…
Low skeletal muscle radiodensity (SMD) is related to higher mortality in several cancers, but the association with colorectal cancer (CRC) prognosis is unclear. This observational study included 3262 men and women from the Kaiser Permanente Northern California population diagnosed between…
The TGFβ-signaling pathway plays an important role in the pathogenesis of colorectal cancer (CRC). Loss of function of several genes within this pathway, such as bone morphogenetic proteins (BMPs) have been seen as key events in CRC progression. In this…
Colorectal cancer (CRC) accounts for about 8% of all new cancer cases diagnosed in the US. We used whole exome sequence data from triplet samples (colon carcinoma, colon adenoma, and normal tissue) from 18 individuals to assess gene mutation rates.…
Nonsteroidal anti-inflammatory drugs (NSAIDs) use has consistently been associated with lower risk of colorectal cancer (CRC); however, studies showed inconsistent results on which cohort of individuals may benefit most. We performed multivariable logistic regression analysis to systematically test for the…
We examined expression of genes in the p53-signaling pathway. We determine if genes that have significantly different expression in carcinoma tissue compared to normal mucosa also have significantly differentially expressed miRNAs. We utilize a sample of 217 CRC cases. We…
Substantial evidence supports an association between use of menopausal hormone therapy and decreased colorectal cancer (CRC) risk, indicating a role of exogenous sex hormones in CRC development. However, findings on endogenous oestrogen exposure and CRC are inconsistent. We used a Mendelian…
Guidelines for initiating colorectal cancer (CRC) screening are based on family history but do not consider lifestyle, environmental, or genetic risk factors. We developed models to determine risk of CRC, based on lifestyle and environmental factors and genetic variants, and…
Muscle abnormalities such as low muscle mass and low muscle radiodensity are well known risk factors for unfavourable cancer prognosis. However, little is known in regard to the degree and impact of longitudinal changes in muscle mass and radiodensity within…
This study is part of the Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) program, which aims to enhance understanding of the implementation and effects of screening as practiced in multiple, heterogeneous health care environments in the United States. Within…
Genome-wide association studies (GWASs) have successfully identified thousands of genetic variants for many complex diseases; however, these variants explain only a small fraction of the heritability. Recently, genetic association studies that leverage external transcriptome data have received much attention and…
JAK-STAT signaling influences many downstream processes that, unchecked, contribute to carcinogenesis and metastasis. MicroRNAs (miRNAs) are hypothesized as a mechanism to prevent uncontrolled growth from continuous JAK-STAT activation. We investigated differential expression between paired carcinoma and normal colorectal mucosa of…
Background: Several epidemiologic studies have reported strong inverse associations between metformin use and risk of colorectal cancer, although time-related biases, such as immortal time bias, may in part explain these findings. We reexamined this association using methods to minimize these…
Effectiveness of fecal occult blood test (FOBT) for colorectal cancer (CRC) screening depends on annual testing, but little is known about patterns of repeat stool-based screening within different settings. Our study's objective was to characterize screening patterns and identify factors…
BACKGROUND & AIMS: The fecal immunochemical test (FIT) is widely used in colorectal cancer (CRC) screening. The OC-Light FIT is 1 of 2 FITs recommended for CRC screening by the Preventive Services Task Force guidelines. However, little is known about…
Apoptosis is genetically regulated and involves intrinsic and extrinsic pathways. We examined 133 genes within these pathways to identify whether they are expressed differently in colorectal carcinoma (CRC) and normal tissue (N = 217) and if they are associated with similar differential…
BACKGROUND: Prediction of histology of small polyps facilitates colonoscopic treatment. The aims of this study were: 1) to develop a simplified polyp classification, 2) to evaluate its performance in predicting polyp histology, and 3) to evaluate the reproducibility of the…
This study aims to 1) evaluate uptake of fecal immunochemical testing among African Americans aged 45 to 49 who receive outreach for such testing by mail, 2) examine the yield of screening results, including advanced adenomas and colon cancers, and…
Sessile serrated adenomas (SSAs) are precursors of 15% to 30% of colorectal cancers but are frequently underdiagnosed. We sought to measure the SSA detection rate (SDR) and predictors of SSA detection after educational training for community gastroenterologists and pathologists. Colonoscopy…
The nuclear factor-kappa B (NF-κB) signalling pathway is a regulator of immune response and inflammation that has been implicated in the carcinogenic process. We examined differentially expressed genes in this pathway and miRNAs to determine associations with colorectal cancer (CRC).…
Background: The Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study offers an important opportunity to advance cancer research by extending the original WHI studies to examine survivorship in women diagnosed with cancer during their participation in WHI.Methods:…
Background: Patients who receive an abnormal cancer screening result require follow-up for diagnostic testing, but the time to follow-up varies across patients and practices.Methods: We used a simulation study to estimate the change in lifetime screening benefits when time to…
Screening colonoscopy's effectiveness in reducing colorectal cancer mortality risk in community populations is unclear, particularly for right-colon cancers, leading to recommendations against its use for screening in some countries. This study aimed to determine whether, among average-risk people, receipt of…
The Wnt-signaling pathway functions in regulating cell growth and thus is involved in the carcinogenic process of several cancers, including colorectal cancer. We tested the hypothesis that multiple genes in this signaling pathway are dysregulated and that miRNAs are associated…
A metastatic cancer diagnosis is associated with high levels of distress in patients and caregivers. Mindfulness interventions can reduce distress and improve quality of life in cancer patients. However, standard mindfulness training relies on in-person instruction, which is often not…
Mitogen-activated protein kinase (MAPK) pathways regulate many cellular functions including cell proliferation and apoptosis. We examined associations of differential gene and microRNA (miRNA) expression between carcinoma and paired normal mucosa for 241 genes in the KEGG-identified MAPK-signaling pathway among 217…
Rectal cancer and its treatment impair survivors' productivity. To assess determinants of market and nonmarket employment, job search, volunteering, and homemaking among survivors five years or longer after diagnosis. We mailed questionnaires to 1063 survivors who were members of (Northern…
The goal of this study is to test a randomized intervention of up to six months of home-based resistance training and protein supplementation versus a waitlist control. The intervention will begin during the first month of chemotherapy and continue through…
Cancer is the second leading cause of death among American Indians and Alaskan Natives (AIAN), although cancer survival information in this population is limited, particularly among urban AIAN. In this retrospective cohort study, we compared all-cause and prostate, breast, lung,…
Often, studies modeling an exposure's influence on time to disease-specific death from study enrollment are incorrectly interpreted as if based on time to death from disease diagnosis. We studied 151,996 postmenopausal women without breast or colorectal cancer in the Women's…
Colonoscopy quality, as measured by adenoma detection rates, varies widely across providers and is inversely related to patients' post-colonoscopy cancer risk. This has unknown consequences for the benefits of faecal immunochemical testing (FIT) vs. primary colonoscopy screening for colorectal cancer.…
Systemic inflammation and sarcopenia are easily evaluated, predict mortality in many cancers, and are potentially modifiable. The combination of inflammation and sarcopenia may be able to identify patients with early-stage colorectal cancer (CRC) with poor prognosis. To examine associations of…
This project will evaluate the effectiveness of screening fecal immunochemical testing (FIT) versus screening colonoscopy in reducing the risk of death from colorectal cancer in average risk men and women who receive their care in community settings. We will also…
Colorectal cancer (CRC) is preventable through screening, with colonoscopy and fecal occult blood testing comprising the two most commonly used screening tests. Given the differences in complexity, risk, and cost, it is important to understand these tests' comparative effectiveness. The…
Annual testing using either a high-sensitivity guaiac fecal occult blood test (HS-gFOBT) or a fecal immunochemical test (FIT) is recommended for screening average-risk people for colorectal cancer. We compared the performance characteristics of the HS-gFOBT Hemoccult II SENSA and two…
Bowel function in long-term rectal cancer survivors with anastomosis has not been characterized adequately. We hypothesized that bowel function is associated with patient, disease, and treatment characteristics. The cohort study included Kaiser Permanente members who were long-term (≥5 years) rectal cancer…
Tumor suppressor genes (TSGs) and oncogenes (OG) are involved in carcinogenesis. MiRNAs also contribute to cellular pathways leading to cancer. We use data from 217 colorectal cancer (CRC) cases to evaluate differences in TSGs and OGs expression between paired CRC…
The PI3K/AKT-signaling pathway is one of the most frequently activated signal-transduction pathways in cancer. We examined how dysregulated gene expression is associated with miRNA expression in this pathway in colorectal cancer (CRC). We used data from 217 CRC cases to…
Fecal immunochemical testing is the most commonly used method for colorectal cancer screening worldwide. However, its effectiveness is frequently undermined by failure to obtain follow-up colonoscopy after positive test results. To evaluate interventions to improve rates of follow-up colonoscopy for…
For some patients, positive cancer screening test results can be a stressful experience that can affect future screening compliance and increase the use of health care services unrelated to medically indicated follow-up. Among 483,216 individuals aged 50 to 75 years…
Oesophageal adenocarcinoma (OA) incidence has risen sharply in Western countries over recent decades. Local and systemic inflammation is considered an important contributor to OA pathogenesis. Established risk factors for OA and its precursor, Barrett's oesophagus (BE), include symptomatic reflux, obesity…
Characterization of gene-environment interactions (GEIs) in cancer is limited. We aimed at identifying GEIs in rectal cancer focusing on a relevant biologic process involving the angiogenesis pathway and relevant environmental exposures: cigarette smoking, alcohol consumption, and animal protein intake. We…
For many chemotherapy regimens dosed based on body surface area (BSA), patients experience dose reductions or delays or discontinue treatment, thereby reducing survival. Consideration of body composition may be useful in individualizing chemotherapy dosing, but to the authors' knowledge few…
Recent studies report racial disparities among individuals in organized colorectal cancer (CRC) programs; however, there is a paucity of information on CRC screening utilization by race/ethnicity among newly age-eligible adults in such programs. This was a retrospective cohort study among…
This study will evaluate the effectiveness of screening fecal immunochemical testing (FIT) versus screening colonoscopy in reducing the risk of death from colorectal cancer in average risk men and women who receive their care in community settings. We will also…
This document updates the colorectal cancer (CRC) screening recommendations of the U.S. Multi-Society Task Force of Colorectal Cancer (MSTF), which represents the American College of Gastroenterology, the American Gastroenterological Association, and The American Society for Gastrointestinal Endoscopy. CRC screening tests…
Background: Body composition may partially explain the U-shaped association between body mass index (BMI) and colorectal cancer survival.Methods: Muscle and adiposity at colorectal cancer diagnosis and survival were examined in a retrospective cohort using Kaplan-Meier curves, multivariable Cox regression, and…
The goal of this study was to determine response rates and associated costs of different survey methods among colorectal cancer (CRC) survivors. We assembled a cohort of 16,212 individuals diagnosed with CRC (2010-2014) from six health plans, and randomly selected…
The US Multi-Society Task Force on Colorectal Cancer, with invited experts, developed a consensus statement and recommendations to assist health care providers with appropriate management of patients with biallelic mismatch repair deficiency (BMMRD) syndrome, also called constitutional mismatch repair deficiency syndrome. This position…
The US Multi-Society Task Force on Colorectal Cancer, with invited experts, developed a consensus statement and recommendations to assist health care providers with appropriate management of patients with biallelic mismatch repair deficiency (BMMRD) syndrome, also called constitutional mismatch repair deficiency…
The fecal immunochemical test (FIT) is commonly used for colorectal cancer screening and positive test results require follow-up colonoscopy. However, follow-up intervals vary, which may result in neoplastic progression. To evaluate time to colonoscopy after a positive FIT result and…
The aims of this study are: 1) To build a comprehensive risk-prediction model for colorectal cancer and advanced adenoma in 45,000 colorectal tumors and 45,000 controls based on existing common and rare genome-wide genetic variants, demographic characteristics, and lifestyle and…
Endoscopist fatigue may impact colonoscopy quality, but prior studies conflict, and minimal data exist from community-based practices where most colonoscopies are performed. Within a large, community-based integrated healthcare system, we evaluated the associations among 4 measures of endoscopist fatigue and…
Fecal immunochemical test (FIT) screening detects most asymptomatic colorectal cancers. Combining FIT screening with stool-based genetic biomarkers increases sensitivity for cancer, but whether DNA biomarkers (biomarkers) differ for cancers detected versus missed by FIT screening has not been evaluated in…
With increasing age of HIV patients, HIV care is increasingly directed towards prevention of chronic disease, including cancer. With the exception of our recent study, prior research has not noted a higher risk of colorectal cancer in HIV patients. However,…
This study will provide evidence on the prevalence and prognostic value of sarcopenia at diagnosis among KPNC colorectal cancer patients diagnosed from 2005-2013. Sarcopenia will be assessed through the qualitative determination of an expert radiologist using visual inspection, and validated…
The purpose of this study is to assess the efficacy of the computational method MeScore CRC in risk stratification for colorectal cancer in a seemingly healthy population (average risk).
The prevalence of metabolically unhealthy phenotype in normal-weight adults is 30%, and few studies have explored the association between metabolic phenotype and colorectal cancer incidence in normal-weight individuals. Our aim was to compare the risk of colorectal cancer in normal-weight…
A case-control study to evaluate the associations between commonly performed tests (e.g. colonoscopy) and mortality from colon cancer.
An evaluation of the entire colorectal cancer screening process to optimize end results. The study includes evaluation of screen-failures (persons who had cancer detected outside of screening), failures of colonoscopy detection (and causes), and differences between screen detected and non-screen…
Using a novel state of the art meausre of lean body mass and fat mass derived from CT scans , this study will examine effects of body composition and changes in body composition among colon cancer survivors on colon cancer…
This is a case-control study to evaluate the associations between commonly performed tests (e.g., colonoscopy) and mortality from colon cancer.
Fecal immunochemical tests (FITs) are widely used in colorectal cancer (CRC) screening, but hemoglobin degradation, due to exposure of the collected sample to high temperatures, could reduce test sensitivity. We examined the relation of ambient temperature exposure with FIT positivity…
The use of the fecal occult blood test (FOBT) for colorectal cancer (CRC) screening is supported by randomized trials demonstrating effectiveness in cancer prevention and widely recommended by guidelines for this purpose. The fecal immunochemical test (FIT), as a direct…
Higher body mass index (BMI) is associated with incident colorectal cancer but not consistently with colorectal cancer survival. Whether weight gain or loss is associated with colorectal cancer survival is largely unknown. We identified 2,781 patients from Kaiser Permanente Northern…
Screening outreach programs using population health management principles offer services uniformly to all eligible persons, but racial/ethnic colorectal cancer (CRC) screening patterns in such programs are not well known. To examine the association between race/ethnicity and the receipt of CRC…
Types of surgery for rectal cancer (RC), including permanent ostomy (PO) or temporary ostomy followed by anastomosis (TO) or initial anastomosis (AN), can affect psychological and financial well-being during active treatment. However, these relationships have not been well studied among…
Racial and ethnic diversity has historically been difficult to achieve in National Cancer Institute-sponsored clinical trials, even while as many as 80% of those trials have faced difficulty in meeting overall recruitment targets. In an attempt to address these issues,…
Population outreach strategies are increasingly used to improve colorectal cancer (CRC) screening. The influence of primary care on cancer screening in this context is unknown. To assess associations between primary care provider (PCP) visits and receipt of CRC screening and…
Delays in diagnostic testing after a positive result from a screening test can undermine the benefits of colorectal cancer (CRC) screening, but there are few empirical data on the effects of such delays. We used microsimulation modeling to estimate the…
To produce evidence capable of informing healthcare decision making at all critical levels, pragmatic clinical trials are diverse both in terms of the type of intervention (medical, behavioral, and/or technological) and the target of intervention (patients, clinicians, and/or healthcare system…
The effects of obesity and metabolic dysregulation on cancer survival are inconsistent. To identify high-risk subgroups of obese patients and to examine the joint association of metabolic syndrome (MetSyn) in combination with obesity, we categorized patients with early-stage (I to…
Higher body mass index (BMI) is a well-established risk factor for colorectal cancer (CRC), but is inconsistently associated with CRC survival. In 6 prospective studies participating in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), 2,249 non-Hispanic white CRC…
Expert recommendations differ for colorectal cancer screening in the elderly. Recent studies suggest that healthy adults aged >75 years may benefit from screening. This study examined screening use and follow-up, and how they varied by health status within age strata,…
Physicians and investigators have sought to determine the relationship between body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]) and colorectal cancer (CRC) outcomes, but methodologic limitations including sampling selection bias, reverse causality, and…
This study was conducted in the Kaiser Permanente Medical Care Program of Northern California to identify patient characteristics that explain interest in flexible sigmoidoscopy (FS) screening. A mailed screening invitation to 6837 age-eligible patients elicited responses from 49%. Efforts to…
Few Asian-American women participate in cancer treatment trials. In a pilot study to assess barriers to participation, we mailed surveys to 132 oncologists and interviewed 19 Asian-American women with cancer from Northern California. Forty-four oncologists responded. They reported as barriers…
BACKGROUND: Optimizing breast and cervical cancer screening rates within health plans requires clinician support for screening guidelines, an awareness of whether there are tools available and functioning to aid screening implementation, and a perception of collegial and leadership support for…
BACKGROUND: Minimal research is available that examines how women at high risk for breast cancer make choices about chemoprevention. We examined how women decide whether to use chemoprevention within the Study of Tamoxifen and Raloxifene (STAR), a non-placebo arm prevention…
Sexual dysfunction is a treatment sequela in survivors of rectal cancer (RC). Differences in health-related quality of life (HRQOL) can occur based on ostomy status (permanent ostomy vs anastomosis). To describe alterations in sexual function and HRQOL based on ostomy…
The fecal immunochemical test (FIT) is a common method for colorectal cancer (CRC) screening, yet its acceptability and performance over several rounds of annual testing are largely unknown. To assess FIT performance characteristics over 4 rounds of annual screening. Retrospective…
Primary care providers and health systems have prominent roles in guiding effective cancer screening. To characterize variation in screening abnormality rates and timely initial follow-up for common cancer screening tests. Population-based cohort undergoing screening in 2011, 2012, or 2013 at…
New screening tests for colorectal cancer continue to emerge, but the evidence needed to justify their adoption in screening programs remains uncertain. A review of the literature and a consensus approach by experts was undertaken to provide practical guidance on…
The US Multi-Society Task Force has developed updated recommendations to guide health care providers with the surveillance of patients after colorectal cancer (CRC) resection with curative intent. This document is based on a critical review of the literature regarding the…
Interventions to improve physician adenoma detection rates for colonoscopy have generally not been successful, and there are little data on the factors contributing to variation that may be appropriate targets for intervention. We sought to identify factors that may influence…
To examine the rates of colorectal cancer (CRC) following a negative screening sigmoidoscopy. Cohort study. An integrated healthcare delivery organisation in California, USA. 72,483 men and women aged 50?years and above who had a negative screening sigmoidoscopy between 1994 and…
Menopausal hormone therapy (MHT) use has been consistently associated with a decreased risk of colorectal cancer (CRC) in women. Our aim was to use a genome-wide gene-environment interaction analysis to identify genetic modifiers of CRC risk associated with use of…
Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk…
Proton pump inhibitors (PPIs) have been shown to be carcinogenic in rodent studies. As part of a long-term post-marketing surveillance study requested by the US Food and Drug Administration, to compare incidence rates of gastric and other cancers after sustained…
Genome-wide association studies have identified several germline single nucleotide polymorphisms (SNPs) significantly associated with colorectal cancer (CRC) incidence. Common germline genetic variation may also be related to CRC survival. We used a discovery-based approach to identify SNPs related to survival…
Bowel dysfunction is a known complication of colorectal cancer (CRC) surgery. Poor bowel control has a detrimental impact on survivors' health-related quality of life (HRQOL). This analysis describes the dietary and behavioral adjustments used by CRC survivors to manage bowel…
Screening colonoscopy's effectiveness in reducing risk of death from right colon cancers remains unclear. Methodological challenges of existing observational studies addressing this issue motivated the design of 'Effectiveness of Screening for Colorectal Cancer in Average-Risk Adults (SCOLAR)'. SCOLAR is a…
Existing literature suggests that metformin, the most commonly used biguanide, may lower colorectal cancer risk. Because most colorectal cancers originate in precancerous adenomas, we examined whether metformin use lowered colorectal adenoma risk after polypectomy in patients with type-2 diabetes. Retrospective…
Evidence of the association between chronic inflammation and the risk of colorectal cancer (CRC) and other obesity-related cancers (OBRC) remains inconsistent, possibly due to a paucity of studies examining repeated measures of inflammation. In the Health ABC prospective study of…
Genetic association studies have traditionally focused on associations between individual single nucleotide polymorphisms (SNPs) and disease. Standard analysis ignores interactions between multiple SNPs and environmental exposures explaining a small portion of disease heritability: the often-cited issue of "missing heritability." We…
Although colorectal cancer (CRC) is a common cause of cancer-related death, it is fortunately amenable to screening with faecal tests for occult blood and endoscopic tests. Despite the evidence for the efficacy of guaiac-based faecal occult blood tests (gFOBT), they…
MicroRNAs (miRNAs) have been implicated in colorectal cancer (CRC) development and associated with prognostic indicators such as disease stage and survival. Prognostic associations are often based on few individuals and imprecise. In this study, we utilize population-based data from 1,141…
Improving colorectal cancer (CRC) screening rates for patients from socioeconomically disadvantaged backgrounds is a recognized public health priority. Our aim was to determine if implementation of a system-wide screening intervention could reduce disparities in the setting of improved overall screening…
The National Colorectal Cancer Roundtable, a national coalition of public, private, and voluntary organizations, has recently announced an initiative to increase colorectal cancer (CRC) screening rates in the United States to 80% by 2018. The authors evaluated the potential public…
High body mass index (BMI) is consistently linked to increased risk of colorectal cancer for men, whereas the association is less clear for women. As risk estimates from observational studies may be biased and/or confounded, we conducted a Mendelian randomization…
Colonoscopy is the most commonly used colorectal cancer screening test in the United States. Its quality, as measured by adenoma detection rates (ADRs), varies widely among physicians, with unknown consequences for the cost and benefits of screening programs. To estimate…
Reliable estimates of adenoma detection rates (ADRs) are needed to inform colonoscopy quality standards, yet little is known about the contributions of patient demographics to variation in ADRs. We evaluated the effects of adjusting for patient age, race/ethnicity, and family…
Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with lower risk of colorectal cancer. To identify common genetic markers that may confer differential benefit from aspirin or NSAID chemoprevention, we tested gene?×?environment interactions between regular use of…
Inflammation is a process central to carcinogenesis and in particular to colorectal cancer (CRC). Previously, we developed a dietary inflammatory index (DII) from extensive literature review to assess the inflammatory potential of diet. In the current study, we utilized this…
Accurate determination of colonoscopy indication is required for managing clinical programs and performing research; however, existing algorithms that use available electronic databases (eg, diagnostic and procedure codes) have yielded limited accuracy. To develop and validate an algorithm for classifying colonoscopy…
Screening is a major contributor to colorectal cancer (CRC) mortality reductions in the United States but is underused. We estimated the fraction of CRC deaths attributable to nonuse of screening to demonstrate the potential benefits from targeted interventions. The established…
Inflammatory cytokines in the colonic microenvironment have been shown to increase with advance colorectal cancer disease state. However, the contribution of inflammatory cytokines to pre-malignant disease, such as the formation of adenomas, is unclear. Using the Milliplex® MAP Human Cytokine/…
The one-sample fecal immunochemical test (FIT) is gaining popularity for colorectal cancer (CRC) screening of average-risk people. However, uptake and annual use remain suboptimal. In 2013, we mailed questionnaires to three groups of nonHispanic White, Black, and Latino Kaiser Permanente…
Red meat intake has been associated with risk of colorectal cancer, potentially mediated through heterocyclic amines. The metabolic efficiency of N-acetyltransferase 2 (NAT2) required for the metabolic activation of such amines is influenced by genetic variation. The interaction between red…
There is a wide choice of fecal occult blood tests (FOBTs) for colorectal cancer screening. GOAL: To highlight the issues applicable when choosing a FOBT, in particular which FOBT is best suited to the range of screening scenarios. Four scenarios…
Examination of reliability and validity of a specialized health-related quality of life questionnaire for rectal cancer (RC) survivors (?5 years post-diagnosis). We mailed 1,063 Kaiser Permanente (KP) RC survivors (313 ostomy and 750 anastomosis) a questionnaire containing the Modified City…
The quality of the bowel preparation directly influences colonoscopy effectiveness. Quality indicators are widely employed to monitor operator performance and to gauge colonoscopy effectiveness. Some have suggested that the enumeration of the mean number of adenomas per colonoscopy (MNA) may…
Patients with inflammatory bowel disease (IBD) have a higher risk of developing colorectal cancer than the general population. Genome-wide association studies have identified and replicated several loci associated with risk of IBD; however, it is currently unknown whether these loci…
Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) that are associated with risk of colorectal cancer. Prior research has evaluated the presence of gene-environment interaction involving the first 10 identified susceptibility loci, but little work has been conducted…
The Multi-Society Task Force, in collaboration with invited experts, developed guidelines to assist health care providers with the appropriate provision of genetic testing and management of patients at risk for and affected with Lynch syndrome as follows: Figure 1 provides…
The Multi-Society Task Force, in collaboration with invited experts, developed guidelines to assist health care providers with the appropriate provision of genetic testing and management of patients at risk for and affected with Lynch syndrome as follows: provides a colorectal…
The Multi-Society Task Force, in collaboration with invited experts, developed guidelines to assist health care providers with the appropriate provision of genetic testing and management of patients at risk for and affected with Lynch syndrome as follows: Figure 1 provides…
A sizable fraction of colorectal cancer (CRC) is expected to be explained by heritable factors, with heritability estimates ranging from 12 to 35% twin and family studies. Genome-wide association studies (GWAS) have successfully identified a number of common single-nucleotide polymorphisms…
To the Editor: Imperiale and colleagues evaluate the use of a single-application multitarget stool DNA test for colorectal-cancer screening and compare its performance characteristics with those of the FIT. Two important points warrant further discussion. First, the investigators used a…
Reducing colorectal cancer mortality by promoting screening has been a national goal for two decades. The NCI's Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium is the first federal initiative to foster coordinated, transdisciplinary research evaluating the entire cancer…
The journey from diagnosis through treatment to survivorship can be challenging for colorectal cancer (CRC) survivors with permanent ostomies. Memories of both the positive and negative health-care interactions can persist years after the initial diagnosis and treatment. The purpose of…
Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers.…
The proportion of screening colonoscopic examinations performed by a physician that detect one or more adenomas (the adenoma detection rate) is a recommended quality measure. However, little is known about the association between this rate and patients' risks of a…
An accurate, noninvasive test could improve the effectiveness of colorectal-cancer screening. We compared a noninvasive, multitarget stool DNA test with a fecal immunochemical test (FIT) in persons at average risk for colorectal cancer. The DNA test includes quantitative molecular assays…
Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary…
Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. CRC incidence and mortality can be reduced through screening. However, in the United States, screening participation remains suboptimal, particularly among underserved populations such as the uninsured, recent immigrants, and…
Fecal immunochemical tests for hemoglobin (FIT) are changing the manner in which colorectal cancer (CRC) is screened. Although these tests are being performed worldwide, why is this test different from its predecessors? What evidence supports its adoption? How can this…
Performance characteristics of fecal immunochemical tests (FITs) to screen for colorectal cancer (CRC) have been inconsistent. To synthesize data about the diagnostic accuracy of FITs for CRC and identify factors affecting its performance characteristics. Online databases, including MEDLINE and EMBASE,…
Epidermal growth factor receptor (EGFR) inhibitors are approved for treating metastatic colorectal cancer (CRC); KRAS mutation testing is recommended prior to treatment. We conducted a non-inferiority analysis to examine whether KRAS testing has impacted survival in CRC patients. We included…
Accurate indication classification is critical for obtaining unbiased estimates of colonoscopy effectiveness and quality improvement efforts, but there is a dearth of published systematic classification approaches. The objective of this study was to evaluate the effects of data-source and adjudication…
To examine whether use of insulin glargine, compared with another long-acting insulin, is associated with risk of breast, prostate, colorectal cancer, or all cancers combined. Computerized health records from Kaiser Permanente Northern and Southern California regions starting in 2001 and…
Recent discoveries promise increasingly to help oncologists individually tailor anticancer therapy to their patients' molecular tumor characteristics. One such promising molecular diagnostic is Kirsten ras (KRAS) tumor mutation testing for metastatic colorectal cancer (mCRC) patients. In the current study, we…
To estimate the expected magnitude of error produced by uncontrolled confounding from health behaviours in observational medical record-based studies evaluating effectiveness of screening colonoscopy. We used data from the prospective National Institutes of Health American Association of Retired Persons (NIH-AARP)…
Experimental evidence has demonstrated an antineoplastic role for vitamin D in the colon, and higher circulating 25-hydroxyvitamin D [25(OH)D] levels are consistently associated with a lower risk of colorectal cancer. Genome-wide association studies have identified loci associated with levels of…
Colorectal cancer (CRC) screening guidelines recommend screening schedules for each single type of test except for concurrent sigmoidoscopy and fecal occult blood test (FOBT). We investigated the cost-effectiveness of a hybrid screening strategy that was based on a fecal immunological…
Pancreatic phospholipase A2, product of PLA2G1B, catalyzes the release of fatty acids from dietary phospholipids.Diet is the ultimate source of arachidonic acid in cellular phospholipids, precursor of eicosanoid signaling molecules, linked to inflammation, cell proliferation and colorectal carcinogenesis. We evaluated…
OBJECTIVES: We tested the effectiveness of offering home fecal immunochemical tests (FITs) during influenza vaccination clinics to increase colorectal cancer screening (CRCS). METHODS: In a clinical trial at Kaiser Permanente Northern California influenza clinics in Redwood City, Richmond, South San…
Arachidonate lipoxygenase (ALOX) enzymes metabolize arachidonic acid to generate potent inflammatory mediators and play an important role in inflammation-associated diseases. We investigated associations between colorectal cancer risk and polymorphisms in ALOX5, FLAP, ALOX12, and ALOX15, and their interactions with nonsteroidal…
SCOPE: The importance of folate-mediated one-carbon metabolism (FOCM) in colorectal carcinogenesis is emphasized by observations that high dietary folate intake is associated with decreased risk of colon cancer (CC) and its precursors. Additionally, polymorphisms in FOCM-related genes have been repeatedly…
BACKGROUND & AIMS: Heritable factors contribute to the development of colorectal cancer. Identifying the genetic loci associated with colorectal tumor formation could elucidate the mechanisms of pathogenesis. METHODS: We conducted a genome-wide association study that included 14 studies, 12,696 cases…
BACKGROUND: The effectiveness of screening colonoscopy in average-risk adults is uncertain, particularly for right colon cancer. OBJECTIVE: To examine the association between screening colonoscopy and risk for incident late-stage colorectal cancer (CRC). DESIGN: Nested case-control study. SETTING: Four U.S. health…
BACKGROUND & AIMS: Reliable community-based colorectal adenoma prevalence estimates are needed to inform colonoscopy quality standards and to estimate patient colorectal cancer risks; however, minimal data exist from populations with large numbers of diverse patients and examiners. METHODS: We evaluated…
BACKGROUND:: Optimizing colorectal cancer (CRC) screening requires identification of unscreened individuals and tracking screening trends. A recent National Institutes of Health State of the Science Conference, 'Enhancing Use and Quality of CRC Screening,' cited a need for more population data…
BACKGROUND: Abnormal mammograms are common, and the risk of false positives is high. We surveyed women in order to understand the factors influencing the efficiency of the evaluation of an abnormal mammogram. METHODS: Women aged 40-80 years, identified from lists…
BACKGROUND: In metastatic colorectal cancer (mCRC), mutations in the KRAS gene predict poor response to EGF receptor (EGFR) inhibitors. Clinical treatment guidelines now recommend KRAS testing if EGFR inhibitors are considered. Our study investigates the clinical uptake and utilization of…
Dietary polyunsaturated fatty acids (PUFAs) can be converted to prostaglandins and leukotrienes. Oxygenation of omega-6 PUFAs generally results in the production of pro-inflammatory mediators, whereas oxygenated products of omega-3 (n-3) PUFAs generally have lower inflammatory activity. We hypothesize that elevated…
The purpose of this article was to describe persistent ostomy-specific concerns and adaptations in long-term (>5 years) colorectal cancer survivors with ostomies. Thirty-three colorectal cancer survivors who participated in 8 gender- and health-related quality of life stratified focus groups and…
BACKGROUND: Considerable evidence suggests that cigarette smoking is associated with a higher risk of colorectal cancer (CRC). What is unclear, however, is the impact of quitting smoking on risk attenuation and whether other risk factors for CRC modify this association.…
For some patients diagnosed with rectal cancer, surgery will involve the creation of a temporary or permanent ostomy. When the colostomy is located in the sigmoid or descending colon, regulation of fecal output can occur through irrigation, a procedure that…
Five patients with primary colorectal adenocarcinoma or anal squamous cell carcinoma were started on a 2-weeks-on, 1-week-off capecitabine dosing regimen in addition to other chemotherapeutic agents and/or radiation. Within the first few doses, patients experienced chest pain and/or dyspnea at…
BACKGROUND & AIMS: The relationship between inflammatory bowel disease (IBD) and the incidence and mortality of colorectal adenocarcinoma (CRC) has not been evaluated recently. METHODS: We calculated the incidence and standardized incidence and mortality rate ratios of CRC among adult…
OBJECTIVES: To evaluate a population outreach program to promote screening for colorectal cancer (CRC) among average-risk insured men and women. STUDY DESIGN: In 2008, 58,440 Kaiser Permanente Colorado members unscreened for CRC received an interactive voice response (IVR) call followed…
Fecal immunochemical tests for hemoglobin are replacing traditional guaiac fecal occult blood tests in population screening programs for many reasons. However, the many available fecal immunochemical test devices use a range of sampling methods, differ with regard to hemoglobin stability,…
Glutathione peroxidases (GPXs) are selenium-dependent enzymes that reduce and, thus, detoxify hydrogen peroxide and a wide variety of lipid hydroperoxides. We investigated tagSNPs in GPX1-4 in relation to colorectal neoplasia in three independent study populations capturing the range of colorectal…
BACKGROUND: The transforming growth factor-beta-signaling pathway has been identified as being involved in colorectal cancer. OBJECTIVE: The aim of this study was to determine how diet and lifestyle factors in combination with genetic variation in the transforming growth factor-beta-signaling pathway…
Genome-wide association studies (GWAS) have identified more than a dozen loci associated with colorectal cancer (CRC) risk. Here, we examined potential effect-modification between single-nucleotide polymorphisms (SNP) at 10 of these loci and probable or established environmental risk factors for CRC…
Inflammatory processes, including, specifically, the inflammatory conditions Crohn's disease (CD) and ulcerative colitis (UC) predispose to colorectal cancer. Interleukin-23 is involved in pro-inflammatory signaling; genetic variation in the interleukin-23 receptor (IL23R) has been consistently associated with CD and UC risk.…
Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility…
Colorectal cancer (CRC) screening is most commonly performed in the United States using an opportunistic approach: patients coming to a physician's office for other unrelated reasons are offered screening with either fecal occult blood tests or, more commonly, a referral…
Genome-wide association studies (GWAS) have successfully identified a number of single-nucleotide polymorphisms (SNPs) associated with colorectal cancer (CRC) risk. However, these susceptibility loci known today explain only a small fraction of the genetic risk. Gene-gene interaction (GxG) is considered to…
The EGFR signaling pathway is involved in carcinogenesis at multiple sites, particularly colorectal cancer, and is a target of colorectal cancer chemotherapy. EGFR signaling is linked to pro-carcinogenic mechanisms, including cell proliferation, survival, angiogenesis, and more recently prostaglandin synthesis. Genetic…
OBJECTIVES: Diabetes mellitus (DM) has been associated with an increased risk of colorectal cancer (CRC). The American College of Gastroenterology Guidelines for Colorectal Cancer Screening 2008 recommend that clinicians be aware of an increased CRC risk in patients with smoking…
BACKGROUND: The transforming growth factor-beta (TGF-beta) signaling pathway is involved in many aspects of tumorigenesis, including angiogenesis and metastasis. The authors evaluated this pathway in association with survival after a diagnosis of colon or rectal cancer. METHODS: The study included…
Although localized colon cancer is often successfully treated with surgery, advanced disease requires aggressive systemic therapy that has lower effectiveness. Approximately 30% to 75% of patients with colon cancer use complementary and alternative medicine (CAM), but there is limited formal…
PURPOSE/OBJECTIVES: To describe how gender shapes the concerns and adaptations of long-term (i.e., more than five years) colorectal cancer survivors with ostomies. DESIGN: Qualitative study using content analysis of focus group content. SETTING: Oregon, southwestern Washington, and northern California. SAMPLE:…
BACKGROUND: Colorectal cancer (CRC) screening rates are low in many areas and cost-effective interventions to promote CRC screening are needed. Recently in a randomized controlled trial, a mailed educational reminder increased CRC screening rates by 16.2% among U.S. Veterans. The…
In 2007, the National Human Genome Research Institute (NHGRI) established the Electronic MEdical Records and GEnomics (eMERGE) Consortium (www.gwas.net) to develop, disseminate, and apply approaches to research that combine DNA biorepositories with electronic medical record (EMR) systems for large-scale, high-throughput…
CYP19A1, or aromatase, influences estrogen-metabolizing enzymes and may influence cancer risk. We examine variation in the CYP19A1 gene and risk of colorectal cancer using data from population-based case-control studies (colon n = 1,574 cases, 1,970 controls; rectal n = 791…
In parallel with our growing understanding of the molecular pathways underlying colorectal neoplasia, significant advances have been made in the treatment of colorectal cancer (CRC). For the past few decades, 5-fluorouracil-based therapy has been the cornerstone of adjuvant therapy. More…
C-reactive protein (CRP), a biomarker of inflammation, has been shown to be influenced by genetic variation in the CRP gene. In this study, we test the hypothesis that genetic variation in CRP influences both the risk of developing colon and…
BACKGROUND: Societal preference-weighted health-related quality of life (HRQOL) scores enable comparing multidimensional health states across diseases and treatments for research and policy. OBJECTIVE: To assess the effects of living with a permanent intestinal stoma, compared with a major bowel resection,…
The Runt-related transcription factors (RUNX), mitogen-activated protein kinase (MAPK) 1 and eukaryotic translation initiation factor 4E (eIF4E) are potentially involved in tumorigenesis. We evaluated genetic variation in RUNX1 (40 tagSNPs), RUNX2 (19 tagSNPs), RUNX3 (9 tagSNPs), MAPK1 (6 tagSNPs), eIF4E…
Bone morphogenetic proteins (BMP) are part of the TGF-beta-signaling pathway; genetic variation in these genes may be involved in colorectal cancer. In this study, we evaluated the association between genetic variation in BMP1 (11 tagSNPs), BMP2 (5 tagSNPs), BMP4 (3…
OBJECTIVE: To determine whether offering home fecal immunochemical tests (FITs) to eligible patients during a high volume influenza vaccination clinic could lead to increased colorectal cancer screening (CRCS) rates in a managed care setting. STUDY DESIGN: Observational study. METHODS: During…
We examined candidate polymorphisms in genes involved in the folate-mediated, one-carbon metabolism pathway, DNMT1 1311V, MTHFD1 R134K and R653Q, MTHFR R594Q, MTR D919G, MTRR H595Y and I22M, SHMT1 L474F, SLC19A1 H27R, and TDG G199S, and associations with rectal tumor characteristics.…
Colorectal cancer (CRC) is an ideal target for early detection and prevention through screening. Noninvasive screening options are the guaiac fecal occult blood test and the fecal immunochemical test. Organized screening offers the promise of uniformly delivering screening to all…
Insulin resistance is thought to mediate the association between obesity and colorectal neoplasia, but no prior studies have assessed stimulated insulin sensitivity as a risk factor for colorectal neoplasia. This prospective study examined the association between insulin sensitivity measured directly…
In an investigation of rectal tumors characterized by CpG island methylator phenotype (CIMP), KRAS2 mutation, and TP53 mutation, we examined associations with dietary and supplemental folate, riboflavin, vitamins B(6) and B(12), and methionine, nutrients involved in folate-mediated 1-carbon metabolism. We…
BACKGROUND: A potential susceptibility locus for colorectal cancer on chromosome 9p24 (rs719725) was initially identified through a genome-wide association study, though replication attempts have been inconclusive. METHODS: We genotyped this locus and explored interactions with known risk factors as potential…
BACKGROUND & AIMS: The absence of grade A supporting evidence for surveillance colonoscopy in patients with ulcerative colitis (UC) has led to controversy regarding its benefit, yet it is routinely recommended in practice guidelines. Limited data are available on rates…
BACKGROUND: Patients with hamartomatous polyposis syndromes have increased risk for colorectal cancer (CRC). Although progression of polyps to carcinoma is observed, pathogenic mechanisms remain unknown. The authors examined whether familial hamartomatous polyps harbor defects in DNA mismatch repair (MMR), and…
Little is known about strategies that physicians use to encourage receipt of colorectal cancer screening (CRCS). This study conducted focus groups with physicians. Twenty-seven physicians participated in four focus groups. Physicians described four categories of approaches: (1) why screening is…
Although fecal immunochemical tests (FITs) have been used for colorectal cancer (CRC) screening in several countries for years, this has not been the case in the United States. The reasons for this are multifactorial, but if the United States hopes…
Diet and lifestyle factors have been inconsistently associated with rectal tumors. It is possible that evaluation of specific tumor markers with these factors may help clarify these associations. In this study, we examine energy contributing nutrients, dietary fiber, BMI (kg/m2),…
PURPOSE: An association between alcohol and rectal cancer has been reported in the epidemiological literature. In this study we further explore the association by examining specific tumor markers with alcohol consumption as well as types of alcoholic beverages consumed. METHODS:…
Genome-wide association studies (GWAS) have identified SMAD7 on 8q21 as being associated with colorectal cancer. We evaluated single nucleotide polymorphisms (SNP) in the SMAD7 gene, including rs4939827, rs12953717, and rs4464148, previously identified from GWAS in a large population-based case-control study…
PURPOSE: Among long-term (>or=5 y) colorectal cancer survivors with permanent ostomy or anastomosis, we compared the incidence of medical and surgical complications and examined the relationship of complications with health-related quality of life. BACKGROUND: The incidence and effects of complications…
Red wine contains polyphenol antioxidants that inhibit colorectal cancer (CRC) development in animal studies. We investigated the effect of red wine intake on risk of CRC in the California Men's Health Study (CMHS). CMHS is a prospective, multiethnic cohort of…
BACKGROUND: Genome-wide association studies and subsequent replication studies have shown that single nucleotide polymorphisms (SNPs) in the chromosomal region 8q24 are associated with colorectal cancer susceptibility. METHODS: We examined 11 SNP markers in the 8q24 region between 128.47 and 128.54…
Calcium, vitamin D, exposure to sunshine, and vitamin D receptor (VDR) genotypes have been associated rectal cancer. We used data from 750 rectal tumors and 1,205 population-based controls examine associations with TP53, KRAS2, and CpG Island methylator phenotype (CIMP) markers.…
BACKGROUND: Activin receptor 2 (ACVR2) is commonly mutated in microsatellite unstable (MSI) colon cancers, leading to protein loss, signaling disruption, and larger tumors. Here, we examined activin signaling disruption in microsatellite stable (MSS) colon cancers.METHODS: Fifty-one population-based MSS colon cancers…
DNA repair enzymes function in major pathways to reverse DNA damage, including base excision repair (BER). Missense polymorphisms in BER repair genes may contribute to differences in DNA repair capacity, specific mutations, and susceptibility to cancer in the presence of…
The MSH6 G39E germline polymorphism is not associated with an increased risk of either microsatellite stable or unstable sporadic colorectal cancer. Other than microsatellite instability, however, most genetic and epigenetic changes of tumors associated with this common variant have not…
OBJECTIVE: High levels of microsatellite instability (MSI-H) have been associated in many studies with improved prognosis in colon cancer. Very few studies have evaluated the effect of MSI-H on rectal cancer survival. We assessed MSI-H and other genetic and epigenetic…
PURPOSE: Intestinal stomas can pose significant challenges for long-term (> or = 5 years) rectal cancer (RC) survivors. Specifying common challenges and sociodemographic or clinical differences will further the development of tailored interventions to improve health-related quality of life (HRQOL).…
Inflammation may be a key element in the etiology of colorectal cancer. In our study, we examine associations between factors related to inflammation and specific rectal cancer mutations. A population-based study of 750 rectal cancer cases with interview and tumor…
BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths in the United States. Randomized controlled trials have shown that annual screening fecal occult blood testing (FOBT) reduces CRC mortality and incidence. However, patient compliance with FOBT…
Genetic association studies investigating the role of vitamin D in colon cancer have primarily focused on the vitamin D receptor (VDR), with limited data available for other genes in the vitamin D pathway, including vitamin D activating enzyme 1-alpha hydroxylase…
BACKGROUND: Data on the number of individuals eligible for screening, and rates of screening, are necessary to assess national colorectal cancer screening efforts. Such data are sparse for safety-net health systems. METHODS: A retrospective cohort study of individuals ages 50…
BACKGROUND: Numerous modifiable factors have been associated with a reduced risk of colorectal cancer, including the chronic use of NSAIDs. Thus, it is biologically plausible that HMG-CoA reductase inhibitors (statins), therapeutic agents that also possess anti-inflammatory effects, are also associated…
Cigarette smoking has been identified as a risk factor for rectal cancer. Our investigation evaluates associations between active and passive smoking and TP53, KRAS2, and BRAF V600E mutations, microsatellite instability (MSI), and CpG Island Methylator Phenotype (CIMP) in rectal tumors.…
Racial and ethnic disparities exist in both incidence and stage detection of colorectal cancer (CRC). We hypothesized that cultural practices (i.e., communication norms and expectations) influence patients' and their physicians' understanding and talk about CRC screening. We examined 44 videotaped…
Colorectal cancer (CRC) screening is widely recommended, but underused. To increase screening rates, we need to implement organized and population-based systems to promote CRC screening among people in a single region, health plan, or health system. This is ideally accomplished…
PURPOSE: The purpose of this analysis was to determine the unique contribution of household income to the variance explained in psychological well-being (PWB) among a sample of colorectal cancer (CRC) survivors. METHODS: This study is a secondary analysis of data…
Variation in genes associated with serum levels of proteins may be useful for examining specific disease pathways. Using data from a large study of colon cancer, we examine genetic variants in insulin, inflammation, estrogen, metabolizing enzymes, and energy homeostasis genes…
Our understanding of somatic alterations in colon cancer has evolved from a concept of a series of events taking place in a single sequence to a recognition of multiple pathways. An oncogenetic tree is a model intended to describe the…
BACKGROUND & AIMS: Thiazolidinedione ligands for peroxisome proliferator-activated receptor gamma (PPARgamma), are used to treat diabetes. PPARgamma is highly expressed in the colon, and exposure to thiazolidinediones has been proposed to affect the risk for colorectal neoplasia. In vitro models…
BACKGROUND: Stool DNA testing is a new approach to colorectal cancer detection. Few data are available from the screening setting. OBJECTIVE: To compare stool DNA and fecal blood testing for detection of screen-relevant neoplasia (curable-stage cancer, high-grade dysplasia, or adenomas…
BACKGROUND: Experimental and epidemiologic studies have suggested that high calcium intake is associated with decreased colon cancer risk, yet very limited data are available for candidate genes in the calcium-vitamin D pathway and colon cancer risk. To address this, we…
The MLH1 -93 G>A promoter polymorphism has been reported to be associated with an increased risk of microsatellite unstable colorectal cancer. Other than microsatellite instability, however, the genetic and most epigenetic changes of tumors associated with this polymorphism have not…
Sarcomatoid carcinomas of the colorectum are rare tumors that display both malignant epithelial and stromal components. Clinically, they are aggressive tumors with early metastasis. Due to their infrequent occurrence, the pathogenesis is poorly understood. We report a case of a…
OBJECTIVES: The objective of this paper is to describe the complex mixed-methods design of a study conducted to assess health-related quality of life (HRQOL) outcomes and ostomy-related obstacles and adjustments among long-term (>5 years) colorectal cancer (CRC) survivors with ostomies…
Two recent case-control studies suggested that some flavonoid subgroups may play a role in preventing colorectal cancer. Previous prospective cohort studies generally reported no association; however, only a small subset of flavonoids was evaluated and partial flavonoid databases were used.…
Polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene have been associated with insulin sensitivity and diabetes, and the TCF7L2 gene is involved in the Wnt/beta-catenin signaling pathway, all factors thought to be important in the etiology of colon cancer.…
BACKGROUND: Lack of confidence in postpolypectomy surveillance guidelines may be a factor in the observed low adherence rates among providers. OBJECTIVE: To assess the 2006 postpolypectomy colonoscopy surveillance guidelines, which recommend 3-year follow-up colonoscopy for individuals with high-risk adenomas (defined…
BACKGROUND: The Women's Health Initiative Dietary Modification (DM) Randomized Controlled Trial evaluated the effects of a low-fat dietary pattern on chronic disease incidence, with breast cancer and colorectal cancer as primary outcomes. The trial protocol also listed ovarian cancer and…
BACKGROUND: One type of fecal occult blood test (FOBT), the unrehydrated guaiac fecal occult blood test (GT), is recommended by the United States Preventive Services Task Force and the Institute of Medicine for use in screening programs, but it has…
This study investigated associations between CpG island methylator phenotype (CIMP) colon cancer and genetic polymorphisms relevant to one-carbon metabolism and thus, potentially the provision of methyl groups and risk of colon cancer. Data from a large, population-based case-control study (916…
Post-polypectomy surveillance is often done sooner than guideline recommendations. This practice is driven by physician intolerance of uncertainty. The accompanying article by Brenner et al. supports the recommendation to wait 5 years or longer following adenoma removal before performing surveillance…
BACKGROUND: As the majority of patients diagnosed with colorectal cancer have no known risk factors, regular screening is strongly recommended. The authors examined factors associated with screening sigmoidoscopy use among participants in the California Men's Health Study (CMHS). METHODS: The…
Thymidylate synthase (TS) is a key enzyme in folate metabolism, a pathway that is important in colorectal carcinogenesis. We investigated the role of functional polymorphisms in the TS 5'-UTR promoter enhancer region (TSER, 3 or 2 repeats of a 28-bp…
BACKGROUND: Standardized reporting systems for diagnostic and screening tests facilitate quality improvement programs and clear communication among health care providers. Although colonoscopy is commonly used for screening, diagnosis, and therapy, no standardized reporting system for this procedure currently exists. The…
Little is known about the contribution of polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) and the folate metabolism pathway in rectal cancer alone. Data were from participants in a case-control study conducted in Northern California and Utah (751 cases and…
Adiposity has been recognized as a risk factor for colorectal adenoma, but the influence of weight gain, adipose tissue distribution, and possible differences between ethnic/racial and gender groups remains unanswered. The aim of this prospective study was to examine the…
BACKGROUND: Despite declining death rates from colorectal cancer (CRC), racial disparities have continued to increase. In this study, the authors examined disparities in a racially diverse group of insured patients. METHODS: This study was conducted among patients who were diagnosed…
It has been proposed that dietary factors such as folate, alcohol and methionine may be associated with colon cancer because of their involvement in DNA methylation processes. Data from a large population-based case-control study of incident colon cancer were used…
BACKGROUND: Information about colonoscopy complications, particularly postpolypectomy bleeding, is limited. OBJECTIVE: To quantify the magnitude and severity of colonoscopy complications. DESIGN: Retrospective cohort. SETTING: Kaiser Permanente of Northern California. PATIENTS: 16, 318 members 40 years of age or older undergoing…
BACKGROUND: Cigarette smoking has been associated with microsatellite instability in sporadic colon cancer. Most microsatellite-unstable colon cancers have widespread methylation of CpG islands (i.e., the CpG island methylator phenotype [CIMP]), and many of these tumors harbor the V600E BRAF mutation.…
The purpose of this study was to test the hypothesis that aspirin use is associated with a decreased risk of incident colorectal cancer. From the Women's Health Initiative, 91,574 participants between the ages of 50 and 79 years at baseline…
Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial…
BACKGROUND AND AIMS: Variant genotypes of uridine diphosphate glucuronsyltransferase isoenzyme 1A6 (UGT1A6) associated with decreased metabolic activity have been associated with an enhanced protective effect of aspirin on the development of colorectal adenomas. However, interactions between UGT1A6 variants or variants…
The transcriptional activity of the vitamin D receptor (VDR) gene is regulated, at least in part, by the androgen receptor (AR) gene. We evaluate how the number of polyglutamine (CAG) repeats of the AR gene influence colorectal cancer in conjunction…
BACKGROUND: Several factors may contribute to poorer prognosis for obese breast cancer patients, including unfavorable disease features, the influence of fat on estrogen availability, co-morbidity, and socio-demographic factors. Both obesity and estrogen receptor negative (ER-) tumors are more prevalent in…
Patients with resected colorectal cancer are at risk for recurrent cancer and metachronous neoplasms in the colon. This joint update of guidelines by the American Cancer Society and the US Multi-Society Task Force on Colorectal Cancer addresses only the use…
