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…
Identify KPNC patients with metastatic/incurable cancer for testing of tumors by next generation sequencing (NGS). NGS screening protocol is aligned to a portfolio of pharma-sponsored therapeutic protocols open now or theoretically open in the future, in addition to treatment off…
The goal of this project is to identify the optimal IBIS model that maximizes screening benefits and minimizes harms. We hypothesize that the “full” model (with all breast cancer risk factors) has better calibration/discrimination compared to a reduced model that…
The goal of this project is to determine whether Ki-67 testing, using newer methods, could be used as a replacement for Oncotype DX testing in selected patients with HR+/HER2- breast cancer.
Improving breast cancer risk prediction models could enable more personalized screening. This would enhance the benefits of screening while limiting the harms. This study will evaluate the performance of multi-feature image risk score models in a large population-based cohort; determine…
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)…
Inadequate representation of diverse racial/ethnic populations in genetic studies is hindering the translational potential of polygenic risk scores (PRS) in cancer risk prediction. To address this shortcoming, we aim to construct and evaluate PRS for cancer and estimate the absolute…
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.
The goal of this project is to determine the best strategy for integrating a home-testing option for cervical cancer screening. The most sensitive screening test for cervical cancer and precancer is a PCR-based test for human papilloma virus (HPV), which…
This study will use follow-up data on women with cervical specimens collected in the KPNC/NCI HPV biorepository and women in the cervical cancer screening program to investigate novel biomarkers of cervical pre-cancer and epidemiology of disease progression from HPV infection…
The Hepatocellular carcinoma (HCC) Early detection Screening (HES) algorithm has been proposed to improve the performance of the serum alpha-fetoprotein (AFP) test in surveillance for HCC. The HES algorithm incorporates data on age, level of alanine aminotransferase, platelet count, and…
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.
Risk of cutaneous squamous cell carcinoma (cSCC) after the diagnosis of actinic keratosis (AK) has not been studied during long follow-up periods. To estimate the risk up to 10 years and identify risk factors for cSCC development. This longitudinal cohort…
For lung cancer screening to confer mortality benefit, adherence to annual screening with low-dose computed tomography scans is essential. Although the National Lung Screening Trial had an adherence rate of 95%, current data are limited on screening adherence across diverse…
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,…
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…
To develop a longitudinal algorithm combining two biomarkers, CA125 and HE4, for early detection of ovarian cancer in women with BRCA mutations. Women with BRCA mutations and intact ovaries were invited to participate in a novel ovarian cancer early detection…
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…
Most guidelines recommend against PSA-based screening for prostate cancer in men ≥ 70 years of age. Adherence to these guidelines is variable. To determine whether the use of a "Best Practice Advisory" (BPA) intervention within the electronic medical record (EMR)…
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.
Background: There are well-documented disparities in lung cancer outcomes across populations. Lung cancer screening (LCS) has the potential to reduce lung cancer mortality, but for this benefit to be realized by all high-risk groups, there must be careful attention to…
The optimal clinical management of oral precancer remains uncertain. We investigated the natural history of oral leukoplakia, the most common oral precancerous lesion, to estimate the relative and absolute risks of progression to cancer, the predictive accuracy of a clinician's…
Immunohistochemistry screening is a reliable method for identifying women with endometrial cancer who are at risk for Lynch syndrome, but clinical workflows used to implement immunohistochemistry screening protocols can vary by institution. The goal of this study was to investigate…
This study proposes to understand patterns and multilevel determinants of racial/ethnic disparities in Lung Cancer Screening utilization from 2017 onward at KPNC.
This study will comprehensively assess the clinical course of intermediate risk non-muscle invasive bladder cancer (NMIBC) in 291 patients diagnosed at Kaiser Permanente Northern California who are enrolled in the Be-Well Study. Intermediate risk NMIBC is an understudied form of…
Purpose. In 2018, the US Preventive Services Task Force (USPSTF) endorsed three strategies for cervical cancer screening in women ages 30 to 65: cytology every 3 years, testing for high-risk types of human papillomavirus (hrHPV) every 5 years, and cytology…
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.
We previously showed that a food-based empirical dietary inflammatory pattern (EDIP) score is associated with circulating inflammatory biomarkers. Metabolomic profiling of inflammatory diets may therefore provide insights on mechanisms contributing to disease etiology and prognosis. We aimed to elucidate metabolites…
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,…
To strengthen the dietary guidelines for breast cancer survivors, we examine whether at-diagnosis concordance with healthful dietary patterns is associated with recurrence or breast cancer death, or with prognostic biomarkers (i.e., body composition, inflammation or metabolic syndrome). Secondarily, we will…
We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to…
In 2012, the US Preventive Services Task Force (USPSTF) recommended against PSA-based screening for prostate cancer in men of all ages. Following this change, screening declined yet the complete impact on clinical presentation is not well defined in the screen-eligible…
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…
The antipsychotic drug haloperidol has antiproliferative and growth-inhibiting properties on prostate cancer cell lines in vitro by binding the sigma 1 protein. Evidence is needed regarding a possible preventive association in men. To examine whether our epidemiologic data support an…
Weight cycling, defined as intentional weight loss followed by unintentional weight regain, may attenuate the benefit of intentional weight loss on endometrial cancer risk. We summarized the literature on intentional weight loss, weight cycling after intentional weight loss, bariatric surgery,…
The effectiveness and value of teledermatology and face-to-face workflows for diagnosing lesions are not adequately understood. We compared the risks of biopsy and cancer diagnosis among 2 face-to-face workflows (direct referral and roving dermatologist) and 4 teledermatology workflows. Retrospective study…
Background. Men with a low-risk prostate cancer (PCa) should consider observation, particularly active surveillance (AS), a monitoring strategy that avoids active treatment (AT) in the absence of disease progression. Objective. To determine clinical and decision-making factors predicting treatment selection. Design.…
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…
The goal of this proposal is to compare tumor versus normal samples of cutaneous squamous cell carcinoma in a large cohort of approximately 77,578 Kaiser Permanente Northern California members. Our goal is to improve understanding of the mechanisms accounting for…
This study evaluates the safety and efficacy in reducing recurrence of Clostridium difficile infection in adults who had a recurrence within 8 weeks of receiving CP101 or placebo in PRISM3. Subjects who are experiencing recurrent Clostridium difficile infection will undergo…
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…
Early detection of hepatocellular carcinoma (HCC) through surveillance reduces mortality associated with this cancer. Guidelines recommend HCC surveillance every 6 months for patients with cirrhosis, via ultrasonography, with or without measurement of serum level of alpha fetoprotein (AFP). We previously developed…
BACKGROUND: Previous meta-analyses have estimated summary positive associations between clinical prostatitis and prostate cancer. However, none have accounted for detection bias, the possibility for increased prostate cancer screening and detection in men with clinical prostatitis, in their pooled estimates.METHODS: We…
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…
Many cervical cancer screening strategies are now recommended in the United States, but the benefits, harms, and costs of each option are unclear. To estimate the cost-effectiveness of 12 cervical cancer screening strategies. The cross-sectional portion of this study enrolled…
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…
We will conduct assays of a selected panel of cardiac, metabolic, and cancer biomarkers in 3,000 blood samples collected by the MINERVA (MultIethNic Study of BrEast ARterial Calcium Gradation and CardioVAscular Disease) Study and stored at the Kaiser Biobank. The…
There is no consensus regarding the management of benign papillary breast lesions diagnosed on image-guided core needle biopsy (IGCNB). This is a retrospective review of 407 patients within Kaiser Permanente Northern California diagnosed between 2012 and 2013. The study focused…
Cross-sectional data indicate that systemic inflammation is important in oesophageal adenocarcinoma. We conducted a prospective study to assess whether prediagnostic circulating markers of inflammation were associated with oesophageal adenocarcinoma and to what extent they mediated associations of obesity and cigarette…
Best practices to facilitate high-quality shared decision-making for lung cancer screening (LCS) are not well established. In our LCS program, patients are first referred to attend a free group education class on LCS, taught by designated clinician specialists, before a…
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…
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…
Little is known about the effect of evolving risk-based cervical cancer screening and management guidelines on United States (US) clinical practice and patient outcomes. We describe the National Cancer Institute's Population-based Research Optimizing Screening through Personalized Regimens (PROSPR I) consortium,…
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…
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…
Epidemiologic analyses of gabapentin use and cancer risk in Kaiser Permanente Northern California were previously carried out in a collaborative study and independently evaluated in a UK database. To update these epidemiologic analyses with 7.5 more years of follow-up. Case-control…
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…
Little is known about whether gene expression profile (GEP) testing and specific recurrence scores (e.g., medium risk) improve women's confidence in their chemotherapy decision or perceived recurrence risk. We evaluate the relationship between these outcomes and GEP testing. We surveyed…
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…
To determine whether bariatric surgery is associated with a lower risk of cancer. Obesity is strongly associated with many types of cancer. Few studies have examined the relationship between bariatric surgery and cancer risk. We conducted a retrospective cohort study…
There is growing interest from the oncology community to understand how body composition measures can be used to improve the delivery of clinical care for the 18.1 million individuals diagnosed with cancer annually. Methods that distinguish muscle from subcutaneous and…
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…
Reports of a role of postmenopausal estrogen replacement therapy in the development of breast cancer have been inconsistent. Although many epidemiologic studies have failed to show an association between short-term use of estrogen and breast cancer, there are indications that…
The National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases initiated the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) in 2015 (the CPDPC's origin, structure, governance, and research objectives are…
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…
Many antihypertensive drugs (ADs) are photosensitizing, heightening reactivity of the skin to sunlight. Photosensitizing ADs have been associated with lip cancer, but whether they impact the risk of cutaneous squamous cell carcinoma (cSCC) is unknown. To examine the association between…
To identify risk factors associated with Barrett esophagus (BE) for potential improved surveillance and risk reduction. Gastroesophageal reflux disease (GERD) is a known risk factor for esophageal adenocarcinoma, but the ability of GERD symptom frequency and severity to predict presence…
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…
This project will validate whether a clinical tool can predict the presence of Barrett's esophagus and the development of esophageal adenocarcinoma.
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…
Although obesity is an established risk factor for renal cell carcinoma (RCC), it is unclear whether this relationship varies across histologic subtypes. We conducted a nested case-control study within the Kaiser Permanente Northern California (KPNC) health care network, and meta-analysis…
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…
Men who have sex with men who are living with HIV are at highest risk for anal cancer. Our objective was to use empirical data to develop a comprehensive disease simulation model that reflects the most current understanding of anal…
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,…
Much of the controversy surrounding prostate cancer screening is due to the poor predictive value of PSA blood tests and the risks attendant to over-diagnosis. This project aims to develop a risk calculator that uses clinical variables to determine the…
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…
Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in United States, and its incidence is substantially higher in men than women, but the reasons for the difference are unknown. We explored whether common mitochondrial DNA (mtDNA)…
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…
Lung cancer is the leading cause of non-AIDS-defining cancer deaths among HIV-infected individuals. Although lung cancer screening with low-dose computed tomography (LDCT) is endorsed by multiple national organizations, whether HIV-infected individuals would have similar benefit as uninfected individuals from lung…
Previous research has reported associations between social relationships and carcinogenesis. Inflammation is a potential mediator of these associations. To clarify these links for one tumor site, we examined associations between social relationships, circulating inflammation markers, and breast cancer incidence. Among…
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…
Although several modifiable risk factors have been independently associated with risk of breast cancer, few studies have investigated their joint association with breast cancer risk. Using a healthy lifestyle index (HLI) score, we assessed the association of a combination of…
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…
Timely follow-up for positive cancer screening results remains suboptimal, and the evidence base to inform decisions on optimizing the timeliness of diagnostic testing is unclear. This systematic review evaluated published studies regarding time to follow-up after a positive screening for…
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…
Medical castration that interferes with androgen receptor (AR) function is the principal treatment for advanced prostate cancer. However, clinical progression is universal, and tumors with AR-independent resistance mechanisms appear to be increasing in frequency. Consequently, there is an urgent need…
Bladder cancer is one of the top 5 most common cancers diagnosed in the U.S. It is also one of the most expensive cancers to treat through the life course given its high rate of recurrence. While cigarette smoking and…
Understanding the effect of contraceptives on the development of precancerous lesions of the cervix and cervical cancer may provide information that is valuable to women in contraceptive decision-making. The purpose of this study was to evaluate the association between recent…
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…
State-of-the-art cervical cancer prevention includes human papillomavirus (HPV) vaccination among adolescents and screening/treatment of cervical precancer (CIN3/AIS and, less strictly, CIN2) among adults. HPV testing provides sensitive detection of precancer but, to reduce overtreatment, secondary "triage" is needed to predict…
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…
With the recent implementation of lung cancer screening in community-based practice, little is currently known about utilization patterns and outcomes in patients following the initial low-dose computed tomography (CT) screening exam. The primary goals of this study are to 1)…
South Asians (ancestry in India, Pakistan, Bangladesh, or Sri Lanka) may have lower cancer risk than other racial-ethnic groups. To supplement published cohort data suggesting low cancer risk in South Asians. Logistic regression models with 7 covariates to study cancer…
This study developed, validated, and disseminated a generalizable informatics algorithm for detecting breast cancer recurrence and timing using a gold standard measure of recurrence coupled with data derived from a readily available common data model that pools health insurance claims…
Very large international and ethnic differences in cancer rates exist, are minimally explained by genetic factors, and show the huge potential for cancer prevention. A substantial portion of the differences in cancer rates can be explained by modifiable factors, 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…
Background/Purpose As cervical cancer screening shifts from cytology to human papillomavirus (HPV) testing, a major question is the clinical value of identifying individual HPV types. We aimed to validate Onclarity™ (Becton Dickinson Diagnostics, Sparks MD), a nine-channel HPV test recently…
With their longitudinal patient relationships, primary care physicians and their care teams are uniquely situated to promote preventive medicine, including cancer screening. A confluence of forces is driving the demand for the personalization of cancer screening recommendations. Recommendations are increasingly…
With combination-antiretroviral therapy, HIV-infected individuals live longer with an elevated burden of cancer. Given the high prevalence of smoking among HIV-infected populations, we examined the risk of incident cancers attributable to ever smoking cigarettes. Observational cohort of HIV-infected participants with…
In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of…
Human papillomavirus (HPV) DNA methylation testing is a promising triage option for women testing HPV-positive during cervical cancer screening. However, the extent to which methylation indicates precancer for all 12 carcinogenic HPV types has not been evaluated. In this nested…
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…
Many studies suggest a role for cholesterol in cancer development. Serum cholesterol levels have been observed to be low in newly diagnosed lymphoma cases. The objective of these analyses was to examine the time-varying relationship of cholesterol with lymphomagenesis in…
To estimate the risk of cervical intraepithelial neoplasia grade 2, 2-3, 3, adenocarcinoma in situ, or cancer (CIN 2 or worse) among women with human immunodeficiency virus (HIV)- and non-HIV-associated immunosuppression. We performed a case-control study of 20,146 women with…
Abdominal fat may be a better predictor than body mass index (BMI) for risk of metabolically-related diseases, such as diabetes, cardiovascular disease, and some cancers. We sought to validate the percent fat reported on dual energy X-ray absorptiometry (DXA) regional…
The most widely used topical agents for the field-based treatment of multiple actinic keratoses (AKs) are 5-fluorouracil and imiquimod, but their comparative effectiveness has not been assessed in a real-world setting. We compared the effectiveness of 5-fluorouracil and imiquimod in…
We developed comprehensive models to determine risk of Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC) based on genetic and non-genetic factors. We used pooled data from 3288 patients with BE, 2511 patients with EAC, and 2177 individuals without either (controls)…
The major goal of this project is to maintain and expand the San Francisco Mammography Registry and to evaluate the performance of mammography in an ethnically diverse population.
Risk prediction models may be useful for facilitating effective and high-quality decision-making at critical steps in the lung cancer screening process. This review provides a current overview of published lung cancer risk prediction models and their applications to lung cancer…
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.…
Lung cancer screening registries can monitor screening outcomes and improve quality of care. To describe nascent lung cancer screening programs and share efficient data collection approaches for mandatory registry reporting in four integrated health care systems of the National Cancer…
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…
The goal of this study was to determine whether the reduction in cancer risk after bariatric surgery is due to weight loss. A retrospective matched cohort study of patients undergoing bariatric surgery was conducted using data from a large integrated…
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…
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…
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…
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…
Background: Higher socioeconomic position (SEP) has been associated with increased risk of breast cancer. Its relationship with earlier age of pubertal onset, a risk factor for breast cancer, is less clear.Methods: We studied the relationship of SEP to pubertal onset…
Although most cervical human papillomavirus type�16 (HPV16) infections become undetectable within 1-2 years, persistent HPV16 causes half of all cervical cancers. We used a novel HPV whole-genome sequencing technique to evaluate an exceptionally large collection of 5,570 HPV16-infected�case-control samples to…
Background: High mammographic density is strongly associated with increased breast cancer risk. Some, but not all, risk factors for breast cancer are also associated with higher mammographic density.Methods: The study cohort (N = 24,840) was drawn from the Research Program…
Barrett's esophagus (BE) is the key precursor lesion of esophageal adenocarcinoma, a lethal cancer that has increased rapidly in westernized countries over the past four decades. Dietary sugar intake has also been increasing over time, and may be associated with…
Persons with human immunodeficiency virus (HIV) have a 2.8-fold higher risk than HIV-uninfected persons of nonmelanoma skin cancer (NMSC), defined as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Individuals with a prior NMSC history are at increased risk…
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…
To assess physicians' attitudes regarding multiple factors that may influence recommendations for active surveillance (AS) vs active treatment (AT) given the central role physicians play in the treatment decision-making process. We conducted semistructured interviews to assess factors that physicians consider…
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…
AIM: To determine the prevalence of gastrointestinal neoplasia among dermatomyositis patients who underwent an esophagogastroduodenoscopy and/or colonoscopy.METHODS: A cross-sectional study examining the results of upper endoscopy and colonoscopy in adults with dermatomyositis at an urban, university hospital over a ten…
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: Weight cycling, defined by an intentional weight loss and subsequent regain, commonly occurs in overweight and obese women and is associated with some negative health outcomes. We examined the role of various weight-change patterns during early to mid-adulthood and…
The optimal timing for postpolypectomy surveillance for low-risk adenomas, defined as 1-2 small tubular adenomas, has remained a challenge for clinicians and guideline developers over the past 4 decades. From the 1970s to the 1990s, it was common practice for…
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…
Half of US states mandate women be notified if they have dense breasts on their mammogram, yet guidelines and data on supplemental screening modalities are limited. Breast density (BD) refers to the extent that breast tissue appears radiographically dense on…
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…
The purpose of this project is to continue building the San Francisco Mammography Registry maintaining KPNC's participation at the current level.
The CISNET prostate group has been adapting and applying models of prostate cancer natural history and survival to understand how changes in prostate cancer screening and treatment impact disease outcomes. Kaiser Permanente will participate in the third funding cycle of…
The purpose of this project is to expand PROSPR's activities related to screening women for cervical cancer. PROSPR is the National Cancer Institute's Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. This specific application will extend an existing collaboration…
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).
Human papillomavirus vaccination may result in lowered intention to be screened for cervical cancer, potentially leading to gaps in screening coverage and avoidable cervical cancer diagnoses. The purpose of this study was to examine the association between human papillomavirus vaccination…
The majority of breast cancer patients receive endocrine therapy, including aromatase inhibitors known to cause increased bone resorption. Bone-related biomarkers at the time of breast cancer diagnosis may predict future risk of osteoporosis and fracture after endocrine therapy. In a…
The overall goal of this study is to identify optimal cervical cancer screening strategies that minimize associated screening harms, while maximizing benefits. The approach will use decision analytic models and comparative effectiveness analyses to identify novel screening strategies that provide…
There is increasing interest in aligning health insurance benefits with clinical goals, i.e., value-based insurance benefits. Starting in 2010, Kaiser eliminated cost-sharing for preventive services for individual Medicare Advantage subscribers; other Medicare beneficiaries are subject to these changes in 2011.…
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…
Achieving a healthy weight is recommended for all breast cancer survivors. Previous research on postdiagnosis weight change and mortality had conflicting results. We examined whether change in body weight in the 18 months following diagnosis is associated with overall and…
To compare the risk of prostate cancer mortality among men treated with 5- alpha reductase inhibitors (5-ARIs) with those treated with alpha-adrenergic blockers (ABs) in community practice settings. A retrospective matched cohort (N=174,895) and nested case-control study (N=18,311) were conducted…
For unknown reasons, there is huge variability in risk conferred by different HPV types and, remarkably, strong differences even between closely related variant lineages within each type. HPV16 is a uniquely powerful carcinogenic type, causing approximately half of cervical cancer…
The ability to collect data on patients for long periods prior to, during, and after a cancer diagnosis is critical for studies of cancer etiology, prevention, treatment, outcomes, and costs. We describe such data capacities within the Cancer Research Network…
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…
A negative association of statin use with liver cancer risk has been reported frequently. We added laboratory measurements, to our knowledge not included in previous investigations, to a case-control analysis of 2877 case patients and 142 850 matched control subjects…
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…
Phosphodiesterase 5A inhibitors (PDEIs), a common treatment for erectile dysfunction, were recently linked to an increased risk of melanoma. We conducted two parallel case-control studies, using the Danish Nationwide Health Registries (DNHR) and the Kaiser Permanente Northern California (KPNC) electronic…
To investigate whether the impact of postdiagnosis exercise on breast cancer outcomes in women diagnosed with early-stage breast cancer differs on the basis of tumor clinicopathologic and molecular features. Using a prospective design, 6,211 patients with early-stage breast cancer from…
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,…
HPV16 is a common sexually transmitted infection although few infections lead to cervical precancer/cancer; we cannot distinguish nor mechanistically explain why only certain infections progress. HPV16 can be classified into four main evolutionary-derived variant lineages (A, B, C, D) that…
To evaluate the trend in uptake of salpingectomy at the time of hysterectomy and assess physicians' attitudes toward the practice. This was a retrospective cohort study using the electronic medical record to identify women 18 years of age or older…
Gastric intestinal metaplasia and dysplasia are precursor lesions for adenocarcinoma. The risks of progression to malignancy from these lesions are not well characterized, particularly in the US populations. We identified 4,331 Kaiser Permanente Northern California members who were diagnosed with…
The cobas?HPV Test ("cobas", Roche Molecular Systems) detects HPV16 and HPV18 individually, and a pool of 12 other high-risk (HR) HPV types. The test is approved for 1) ASC-US triage to determine need for colposcopy, 2) combined screening with cytology…
Obesity and diabetes have been associated with liver cancer. However, recent US-based studies have suggested a lack of association between obesity and liver cancer among blacks and women. We conducted a nested case-control study within the Multiphasic Health Checkup (MHC)…
Diet modulates inflammation and inflammatory markers have been associated with cancer outcomes. In the Women's Health Initiative, we investigated associations between a dietary inflammatory index (DII) and invasive breast cancer incidence and death. The DII was calculated from a baseline…
Full-field digital mammography (FFDM) has largely replaced film-screen mammography in the US. Breast density assessed from film mammograms is strongly associated with breast cancer risk, but data are limited for processed FFDM images used for clinical care. We conducted a…
We present a systematic screening for identifying associations between prescribed drugs and cancer risk using the high quality Danish nationwide health registries. We identified all patients (cases) with incident cancer in Denmark during 2000-2012 (n=278,485) and matched each case to…
A 21-gene test that predicts recurrence risk among women with hormone receptor positive (HR+), localized breast cancer was nationally recommended in 2007, but we know little about its subsequent impact. We evaluated: a) patient characteristics associated with test use, b)…
Lifestyle factors have been well studied in relation to breast cancer prognosis overall; however, associations of lifestyle and late outcomes (>5 years after diagnosis) have been much less studied, and no studies have focused on estrogen receptor-positive (ER+) breast cancer…
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…
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…
We examined the clinical/pathologic features of ipsilateral second breast cancers (IP-SBCs) following breast-conserving surgery (BCS) for DCIS among community-treated patients and ascertained the degree of correlation between the features of index DCIS and IP-SBC events. From a Cancer Research Network…
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…
Various patient, treatment, and pathologic factors have been associated with an increased risk of local recurrence (LR) following breast-conserving therapy (BCT) for ductal carcinoma in situ (DCIS). However, the strength and importance of individual factors has varied; whether combining factors…
The association between leisure-time physical activity (LTPA) and male breast cancer risk is unclear. In the Male Breast Cancer Pooling Project, with 449 cases and 13,855 matched controls, we used logistic regression with study stratification to generate adjusted ORs and…
Novel health information technology (IT)-based strategies harnessing patient registry data seek to improve care at a population level. We analyzed costs from a randomized trial of 2 health IT strategies to improve cancer screening compared with usual care from the…
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…
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…
The incidence of basal cell carcinomas (BCCs) is increasing globally, but incidence rates in the United States are difficult to quantify because BCCs are not reportable tumors. To estimate annual BCC incidence rates by age, sex, and race/ethnicity to identify…
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…
More than two-thirds of US women are overweight or obese, placing them at increased risk for postmenopausal breast cancer. To investigate in this secondary analysis the associations of overweight and obesity with risk of postmenopausal invasive breast cancer after extended…
Studies suggest pioglitazone use may increase risk of cancers. To examine whether pioglitazone use for diabetes is associated with risk of bladder and 10 additional cancers. Cohort and nested case-control analyses among persons with diabetes. A bladder cancer cohort followed…
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…
Cancer is the second leading cause of death in the United States, with 52% of deaths caused by cancers of the lung and bronchus, female breast, uterine cervix, colon and rectum, oral cavity and pharynx, prostate, and skin (melanoma). In…
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…
Validation of early detection cancer biomarkers has proven to be disappointing when initial promising claims have often not been reproducible in diagnostic samples or did not extend to prediagnostic samples. The previously reported lack of rigorous internal validity (systematic differences…
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…
High mammographic density (MD) is a strong risk factor for breast cancer. Chronic inflammation may be related to breast cancer risk through a mechanism involving the percent of breast area that is dense (percent MD). Longitudinal assessments, however, are lacking…
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…
An efficient approach to characterizing the disease burden of rare genetic variants is to impute them into large well-phenotyped cohorts with existing genome-wide genotype data using large sequenced referenced panels. The success of this approach hinges on the accuracy of…
Determining long-term trends in tumor biomarker expression is essential for understanding aspects of tumor biology amenable to change. Limiting the availability of such data, currently used assays for biomarkers are relatively new. For example, assays for the estrogen receptor (ER),…
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…
The effective management of women with human papillomavirus (HPV)-positive, cytology-negative results is critical to the introduction of HPV testing into cervical screening. HPV typing has been recommended for colposcopy triage, but it is not clear which combinations of high-risk HPV…
Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of…
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…
The Women's Health Initiative (WHI) low-fat (20% kcal) dietary modification (DM) trial (1993-2005) demonstrated a nonsignificant reduction in breast cancer, a nominally significant reduction in ovarian cancer, and no effect on other cancers (mean 8.3 years intervention). Consent to nonintervention…
We investigated pre- to post-diagnosis weight change and functional limitations in a cohort of breast cancer survivors. A cohort of 1,841 early-stage breast cancer survivors provided information on pre- and post-diagnosis weight and physical function on average 2 years post-diagnosis.…
The optimal treatment strategy for ductal carcinoma in situ (DCIS) continues to evolve and should consider the consequences of initial treatment on the likelihood, type, and treatment of recurrences. We conducted a retrospective cohort study using two data sources of…
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…
Breast cancer has a complex etiology that includes genetic, biologic, behavioral, environmental, and social factors. Etiologic factors are frequently studied in isolation with adjustment for confounding, mediating, and moderating effects of other factors. A complex systems model approach may present…
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…
We investigated whether the reported lower incidence of prostate cancer in HIV-positive men is a result of confounding factors or reduced screening. We conducted a cohort study of 17,424 HIV-positive and 182,799 HIV-negative men enrolled in Kaiser Permanente (KP). Subjects…
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…
To determine the invasive recurrence (IR) risk among patients with small, node-negative human epidermal growth factor receptor 2 (HER2) -positive breast cancer. Among 16,975 consecutive patients with invasive breast cancer diagnosed from January 1, 2000, to December 31, 2006, in…
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…
Cancer patients tend to have a higher incidence of herpes zoster (HZ), but little is known about their risk of HZ complications. We conducted a retrospective study of 424 newly diagnosed hematologic (HM, n = 140) and solid tumor malignancy…
The observed association between pioglitazone and bladder cancer could be causal or because of bias in the design of prior studies. We hypothesize that proteinuria testing may lead to detection bias if routine test results for proteinuria lead to a…
Data are lacking to describe gene expression-based breast cancer intrinsic subtype patterns for population-based patient groups. We studied a diverse cohort of women with breast cancer from the Life After Cancer Epidemiology and Pathways studies. RNA was extracted from 1…
Cardiotoxicity is a known complication of certain breast cancer therapies, but rates come from clinical trials with design features that limit external validity. The ability to accurately identify cardiotoxicity from administrative data would enhance safety information. To characterize the performance…
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…
The etiology of male breast cancer is poorly understood, partly because of its relative rarity. Although genetic factors are involved, less is known regarding the role of anthropometric and hormonally related risk factors. In the Male Breast Cancer Pooling Project,…
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,…
Re-examine association of fluoxetine and paroxetine with risk of testicular cancer noted in drug screening, with 4 years more follow-up and expanded study of these and other antidepressant drugs. In the Kaiser Permanente Medical Care Program in Northern California, 906…
To assess the uptake of risk-reducing options for the management of ovarian and breast cancer risk in BRCA mutation carriers in a large community based integrated health system in Northern California. A retrospective cohort of deleterious BRCA mutation carriers (1995-2012)…
To estimate ovarian and peritoneal cancer rates after hysterectomy with and without salpingo-oophorectomy for benign conditions. All patients after hysterectomy for benign disease from 1988 to 2006 in Kaiser Permanente Northern California, an integrated health organization. Incidence rates per 100,000…
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…
Barrett's oesophagus is a precursor lesion of oesophageal adenocarcinoma, a cancer that, in the USA, has increased in incidence over 600% during the past 40 years. Barrett's oesophagus and oesophageal adenocarcinoma are much more common among men than among women;…
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…
Genetic association studies have identified more than a dozen genes associated with risk of pancreatic cancer. Given this genetic heterogeneity, family history can be useful for identifying individuals at high risk for this disease. The goal of this analysis was…
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…
Dietary fiber has several anticarcinogenic effects and is thought to be protective against esophageal cancer. The aim of this systematic review was to quantify the association between dietary fiber and the risk of esophageal cancer by investigating histological subtypes of…
We aimed to identify clinicopathologic factors associated with local recurrence (LR) in a large population of DCIS patients treated with breast-conserving therapy between 1990-2001 in three health plans. Regression methods were used to estimate relative risks (RR) of LR. Among…
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…
Barrett's esophagus with dysplasia is commonly treated with radiofrequency ablation (RFA). Despite its effectiveness, a concern of any ablative technique is the development of subsquamous intestinal metaplasia, which could have potential for future neoplastic progression. To date, 34 cases of…
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…
After excisional treatment, cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) can recur. It is not clear how many negative posttreatment Pap or cotest results are needed to ensure adequate safety against CIN 2+ before returning to extended retesting…
Current US national guidelines recommend beginning screening at age 21 using Pap tests only, with cotesting starting at age 30. To inform the management of Pap test abnormalities among women aged 21 to 24 years, who have extremely low cancer…
New screening guidelines recommend that human papillomavirus (HPV)-negative/atypical squamous cells of undetermined significance (ASC-US) results be considered as equivalent to HPV-negative/Pap-negative results, leading to rescreening in 5 years. However, despite ample data, the routine clinical performance of HPV testing of…
In 2012, the US Preventive Services Task Force (USPSTF) and a consensus of 25 organizations endorsed concurrent cytology and human papillomavirus (HPV) testing ("cotesting") for cervical cancer screening. Past screening and management guidelines were implicitly based on risks defined by…
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…
The large-scale Collaborative Oncological Gene-environment Study (COGS) presents new findings that further characterize the genetic bases of breast, ovarian and prostate cancers. We summarize and provide insights into this collection of papers from COGS and discuss the implications of the…
OBJECTIVE: HIV infection and low CD4+ T-cell count are associated with an increased risk of persistent oncogenic human papillomavirus infection-the major risk factor for cervical cancer. Few reported prospective cohort studies have characterized the incidence of invasive cervical cancer (ICC)…
Low-grade squamous intraepithelial lesion (LSIL) Pap results do not typically lead to human papillomavirus (HPV) testing. HPV triage is not cost-effective because most cases are HPV-positive. However, under new national guidelines recommending cotesting for women aged 30 to 64 years,…
Many carcinogens in tobacco smoke cause DNA damage, and some of that damage can be mitigated by the actions of DNA repair enzymes. In a case-control study nested within the Beta-Carotene and Retinol Efficacy Trial, a randomized chemoprevention trial in…
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: Five-year breast cancer survival rates are lower among Hispanic and African-American women than among Non-Hispanic White women. Differences in breast cancer treatment likely play a role. Adjuvant hormonal therapies increase overall survival among women with hormone receptor-positive breast cancer.…
OBJECTIVE: Significant limitations exist in the timely and complete identification of primary and recurrent cancers for clinical and epidemiologic research. A SAS-based coding, extraction, and nomenclature tool (SCENT) was developed to address this problem. MATERIALS AND METHODS: SCENT employs hierarchical…
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: Given the limited literature, we conducted a study to examine the epidemiology of herpes zoster (HZ) among newly diagnosed cancer patients. METHODS: We identified adult health plan members of Kaiser Permanente Northern California diagnosed with invasive cancer from 2001…
Human epidermal growth factor receptor 2 (HER2) expression is amplified in about 20% of breast cancer tumors, and evaluation of HER2 status should influence therapy selection. A critical gap in our knowledge is the real-world implementation of HER2 testing 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.…
BACKGROUND: In screening pharmaceuticals for possible carcinogenic effects we noted an association between lip cancer risk and the photosensitizing antihypertensive drugs hydrochlorothiazide and nifedipine. In this study, we further characterized the risk of lip cancer associated with these and other…
BACKGROUND: Clinical trials demonstrated that women treated for breast cancer with anthracycline or trastuzumab are at increased risk for heart failure and/or cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We estimated real-world adjuvant anthracycline and trastuzumab use…
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…
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…
Over 40% of women with a preoperative diagnosis of complex atypical hyperplasia (CAH) will have endometrial cancer at hysterectomy. CAH diagnoses are often qualified by comments indicating suspicion of cancer. We examine whether these comments correlate with cancer found at…
BACKGROUND: Breast-conserving surgery (BCS) is the most common treatment for ductal carcinoma in situ (DCIS); however, how often women experience subsequent diagnostic evaluations over time is not known. METHODS: We identified 2948 women with DCIS who were treated with BCS…
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.…
BACKGROUND: Cancer Research Network (CRN) sites use administrative data to populate their Virtual Data Warehouse (VDW). However, information on VDW chemotherapy data validity is limited. The purpose of this study was to assess the validity of VRN chemotherapy data.METHODS: This…
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…
PURPOSE: High doses of gabapentin were associated with pancreatic acinar cell tumors in male Wistar rats, but there is little published epidemiological data regarding gabapentin and carcinogenicity. We explored the association between gabapentin and cancer in a US medical care…
BACKGROUND: Hepatosplenic T-cell lymphoma (HSTCL), a rare and rapidly progressive subtype of peripheral T-cell lymphoma, has been reported following TNF-alpha-blocker therapy. To better understand this relationship, we conducted an epidemiologic study in the Kaiser Permanente membership. METHODS: The retrospective cohort…
The American Cancer Society (ACS) publishes Nutrition and Physical Activity Guidelines to serve as a foundation for its communication, policy, and community strategies and, ultimately, to affect dietary and physical activity patterns among Americans. These Guidelines, published approximately every 5…
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…
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…
Little is known about the relation of multivitamin use to breast cancer outcomes. 2,236 women diagnosed from 1997 to 2000 with early-stage breast cancer (Stage I >/= 1 cm, II, or IIIA) were enrolled about 2 years post-diagnosis, primarily from…
PURPOSE: The contribution of menstrual and reproductive factors to risk of ductal carcinoma (DCIS) of the breast is poorly understood. METHODS: The association between menstrual and reproductive factors and subsequent DCIS risk was examined in Women's Health Initiative (WHI) clinical…
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…
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…
BACKGROUND: Few studies have evaluated the combined impact of following recommended lifestyle behaviors on cancer, cardiovascular disease (CVD) and all-cause mortality, and most included tobacco avoidance. Because 80% of Americans are never or former smokers, it is important to consider…
PURPOSE: Data in epidemiological studies sometimes are collected off-schedule from planned study visits. In an ancillary study to the Study of Women's Health Across the Nation (SWAN), longitudinal breast density data were collected retrospectively from mammograms that were not acquired…
OBJECTIVE: Some preclinical in vivo studies and limited human data suggest a possible increased risk of bladder cancer with pioglitazone therapy. This is an interim report of an ongoing cohort study examining the association between pioglitazone therapy and the risk…
OBJECTIVE: To explore whether treatment with pioglitazone was associated with risk of incident cancer at the 10 most common sites (prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma [NHL], pancreas, kidney/renal pelvis, rectal, and melanoma). RESEARCH DESIGN AND METHODS: A…
IGF1, IGF-binding protein-3 (IGFBP-3), IGFBP-1, insulin, leptin, and adiponectin have been inconsistently associated with breast cancer incidence. We explore how these factors are related to breast cancer recurrence and how tamoxifen treatment is related to IGF1 levels among breast cancer…
BACKGROUND: Diabetes is an emerging public health issue in the US, affecting 11% of Americans over the age of 20, with long-term complications that include cardiovascular disease, retinopathy, neuropathy, and nephropathy. A recent meta-analysis found that bladder cancer incidence was…
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…
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…
In the Women's Health Initiative (WHI) trial of calcium plus vitamin D (CaD), we examined the treatment effect on incidence and mortality for all invasive cancers. Postmenopausal women (N = 36,282) were randomized to 1,000 mg of elemental calcium with…
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…
Incidence rates for oesophageal adenocarcinoma have increased by over 500% during the past few decades without clear reasons. Gastro-oesophageal reflux disease, obesity and smoking have been identified as risk factors, although the demographic distribution of these risk factors is not…
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…
PURPOSE: The optimal method to assess human epidermal growth factor receptor 2 (HER2) status remains highly controversial. Before reporting patient HER2 results, American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines mandate that laboratories demonstrate >/= 95% concordance…
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:…
Although tumor size and lymph node involvement are the current cornerstones of breast cancer prognosis, they have not been extensively explored in relation to tumor methylation attributes in conjunction with other tumor and patient dietary and hormonal characteristics. Using primary…
Epidemiologic evidence suggests that cancer incidence is associated with diabetes as well as certain diabetes risk factors and treatments. This consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of…
OBJECTIVE: To examine whether use of adjuvant therapy varies by race/ethnicity among patients with ductal carcinoma in situ (DCIS) at 3 integrated health plan delivery sites based in California and Massachusetts. STUDY DESIGN: Cross-sectional study nested within a cohort of…
BACKGROUND: It has been reported that fatherhood status may be a risk factor for prostate cancer. In the current study, the authors examined the subsequent occurrence of prostate cancer in a cohort of men evaluated for infertility to determine whether…
