Thomas U. Ahearn
A5045635838- BRCA gene mutations in cancer
- Genetic Associations and Epidemiology
- Global Cancer Incidence and Screening
- Nutrition, Genetics, and Disease
- Cancer Genomics and Diagnostics
- Cancer Risks and Factors
- Prostate Cancer Treatment and Research
- Genetic factors in colorectal cancer
- Breast Cancer Treatment Studies
- Cancer, Lipids, and Metabolism
- Colorectal Cancer Screening and Detection
- Estrogen and related hormone effects
- Cervical Cancer and HPV Research
- Gene expression and cancer classification
- Bioinformatics and Genomic Networks
- Molecular Biology Techniques and Applications
- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Vitamin D Research Studies
- Prostate Cancer Diagnosis and Treatment
- RNA Research and Splicing
- Nutritional Studies and Diet
- Health, Environment, Cognitive Aging
- Ginger and Zingiberaceae research
- Cardiovascular Health and Risk Factors
National Institutes of Health
2018-2025
National Cancer Institute
2017-2025
Division of Cancer Epidemiology and Genetics
2018-2025
Cancer Institute (WIA)
2010-2024
Government of the United States of America
2019-2021
University of Manchester
2021
St Mary's Hospital
2021
Edinburgh Cancer Research
2021
Cancer Research Center
2021
Harvard University
2013-2020
Stratification of women according to their risk breast cancer based on polygenic scores (PRSs) could improve screening and prevention strategies. Our aim was develop PRSs, optimized for prediction estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset empirically validate PRSs in prospective studies. The development comprised 94,075 case subjects 75,017 control European ancestry 69 studies, divided into training validation sets. Samples were...
Genetic testing for breast cancer susceptibility is widely used, but many genes, evidence of an association with weak, underlying risk estimates are imprecise, and reliable subtype-specific lacking.
Background: PTEN is a tumor suppressor frequently deleted in prostate cancer that may be useful prognostic biomarker.However, the association of loss with lethal disease has not been tested large, predominantly surgically treated cohort. Methods:In Health Professionals Follow-up Study and Physicians' Study, we followed 1044 incident cases diagnosed between 1986 2009 for cancer-specific all-cause mortality.A genetically validated immunohistochemistry (IHC) assay was performed on tissue...
Rare germline genetic variants in several genes are associated with increased breast cancer (BC) risk, but their precise contributions to different disease subtypes unclear. This information is relevant guidelines for gene panel testing and risk prediction.To characterize tumors BC susceptibility large-scale population- or hospital-based studies.The multicenter, international case-control analysis of the BRIDGES study included 42 680 patients 46 387 control participants, comprising women...
Vitamin D and calcium affect several pathways involved in inflammation, tumor growth, immune surveillance relevant to carcinogenesis. Also, epidemiologic evidence indicates that vitamin may reduce risk for developing colorectal adenomas cancer. To investigate the effects of on biomarkers inflammation adenoma patients, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 × factorial clinical trial (n = 92) g/d and/or 800 IU/d D(3) supplementation versus placebo over 6 months....
Abstract Background External validation of risk models is critical for risk-stratified breast cancer prevention. We used the Individualized Coherent Absolute Risk Estimation (iCARE) as a flexible tool model development and comparative to make projections population stratification. Methods Performance two recently developed models, one based on Breast Prostate Cancer Cohort Consortium analysis (iCARE-BPC3) another literature review (iCARE-Lit), were compared with established (Breast...
The gut microbiota may play a role in breast cancer etiology by regulating hormonal, metabolic and immunologic pathways. We investigated associations of fecal bacteria with nonmalignant disease case-control study conducted Ghana, country rising incidence mortality. To do this, we sequenced the V4 region 16S rRNA gene to characterize samples collected at time biopsy (N = 379 cases, N 102 414 population-based controls). estimated alpha diversity (observed amplicon sequence variants [ASVs],...
Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or time, genotype, may be causally overall, pre/post-menopause, case-groups defined tumour characteristics.
Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks missense these genes uncertain. We analyzed data on 59,639 cases 53,165 controls from studies participating the Breast Cancer Association Consortium BRIDGES project. sampled training (80%) validation (20%) sets to analyze rare ATM (1146 variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), (472). evaluated according five silico prediction-of-deleteriousness algorithms,...
Abstract Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women the top bottom 1% polygenic risk exhibited ~11 ~14-fold higher risks delayed precocious puberty, respectively. identified several genes harboring rare loss-of-function variants ~200,000 including ZNF483 , which...
Abstract To estimate the effects of ginger on apoptosis, proliferation, and differentiation in normal-appearing colonic mucosa, we randomized 20 people at increased risk for colorectal cancer to 2.0 g or placebo daily 28 days a pilot trial. Overall expression distributions Bax, Bcl-2, p21, hTERT, MIB-1 (Ki-67) crypts rectal mucosa biopsies were measured using automated immunohistochemistry quantitative image analysis. Relative placebo, Bax group decreased 15.6% (P = 0.78) whole crypts, 6.6%...
Abstract Purpose: Breast and prostate cancer co-occur in families, women with a family history of are at increased breast risk. Prostate is among the most heritable cancers, but few studies have investigated its association familial cancer. The objective this study to investigate extent which or first-degree relatives increases Experimental Design: A prospective 37,002 U.S. men Health Professionals Follow-up Study. During 16-year follow-up 2012, 4,208 total 344 lethal cases were diagnosed....
We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases 80 354 controls from Breast Cancer Association Consortium. Interactions were standard logistic regression newly developed case-only method overall by estrogen receptor status. After accounting multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined...
Abstract Background Polygenic risk scores (PRSs) have been demonstrated to identify women of European, Asian, and Latino ancestry at elevated developing breast cancer (BC). We evaluated the performance existing PRSs trained in European populations among African ancestry. Methods assembled genotype data for ancestry, including 9241 case subjects 10 193 control subjects. associations 179- 313-variant with overall subtype-specific BC risk. PRS discriminatory accuracy was assessed using area...
Abstract Background Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations intrinsic-like subtypes are less clear. Methods Analyses included up 23 353 cases 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used estimate association...
PURPOSE A polygenic risk score (PRS) consisting of 313 common genetic variants (PRS ) is associated with breast cancer and contralateral cancer. This study aimed to evaluate the association PRS clinicopathologic characteristics of, survival following, METHODS Women invasive were included, 98,397 European ancestry 12,920 Asian ancestry, from Breast Cancer Association Consortium (BCAC), 683 women MINDACT trial. Associations between characteristics, including 70-gene signature for MINDACT,...
Abstract Data sharing is essential for reproducibility of epidemiologic research, replication findings, pooled analyses in consortia efforts, and maximizing study value to address multiple research questions. However, barriers related confidentiality, costs, incentives often limit the extent speed data sharing. Epidemiological practices that follow Findable, Accessible, Interoperable, Reusable (FAIR) principles can these by making resources findable with necessary metadata, accessible...
Obesity is associated with an increased risk of fatal prostate cancer. We aimed to elucidate the importance and relevant timing obesity weight change for cancer progression. identified 5,158 men diagnosed localized (clinical stage T1/T2) from 1986 2012 in Health Professionals Follow‐up Study. Men were followed biochemical recurrence lethal (development distant metastasis or cancer‐specific mortality) until 2012. Cox regression estimated hazard ratios (HRs) body mass index (BMI) at age 21,...
Cytotoxic chemotherapy remains the main systemic therapy for gastro-oesophageal adenocarcinoma, but resistance to is common, resulting in ineffective and often toxic treatment patients. Predictive biomarkers response would increase probability of successful therapy, none are currently recommended clinical use. We used global gene expression profiling tumour biopsies identify novel predictive cytotoxic chemotherapy. Tumour from patients (n=14) with TNM stage IB–IV adenocarcinomas receiving...