ArticlePLoS genetics2010
Common genetic variants and modification of penetrance of BRCA2-associated breast cancer.
Article in PLoS genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 57 papers, 2 of them syntheses that pooled it.
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Who cites it
57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 163 citations in OpenAlex.
- Post-GWAS gene-environment interplay in breast cancer: results from the Breast and Prostate Cancer Cohort Consortium and a meta-analysis on 79,000 women.Human molecular genetics · 2014Pooled it
- Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis.Journal of the National Cancer Institute · 2014Pooled it
- Putative linkage signals identified for breast cancer in African American families.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2015Trial
- CommonGenome research · 2025Article
- Insights into genetic modifiers of breast cancer risk in carriers of BRCA1 and BRCA2 pathogenic variants.Hereditary cancer in clinical practice · 2025Review
- Complex traits and candidate genes: estimation of genetic variance components across multiple genetic architectures.G3 (Bethesda, Md.) · 2023Article
- A systematic review and meta-analysis of the association between HOTAIR polymorphisms and susceptibility to breast cancer.Archives of medical science : AMS · 2023Review
- Average semivariance yields accurate estimates of the fraction of marker-associated genetic variance and heritability in complex trait analyses.PLoS genetics · 2021Article
- Immune cells lacking Y chromosome show dysregulation of autosomal gene expression.Cellular and molecular life sciences : CMLS · 2021Article
- Predicting Breast Cancer Gene Expression Signature by Applying Deep Convolutional Neural Networks From Unannotated Pathological Images.Frontiers in oncology · 2021Article
- Breast Cancer-Related Low Penetrance Genes.Advances in experimental medicine and biology · 2021Article
- Illustrating Cancer Risk: Patient Risk Communication Preferences and Interest regarding a Novel BRCA1/2 Genetic Risk Modifier Test.Public health genomics · 2020Article
- Identification of two novel breast cancer loci through large-scale genome-wide association study in the Japanese population.Scientific reports · 2019Article
- Exploring genetic counselors' perceptions of usefulness and intentions to use refined risk models in clinical care based on the Technology Acceptance Model (TAM).Journal of genetic counseling · 2019Article
- Genetic Testing to Guide Risk-Stratified Screens for Breast Cancer.Journal of personalized medicine · 2019Review
- Evaluation of significant genome-wide association studies risk - SNPs in young breast cancer patients.PloS one · 2019Article
- Polymorphisms of long non-coding RNA HOTAIR with breast cancer susceptibility and clinical outcomes for a southeast Chinese Han population.Oncotarget · 2018Article
- Genetics of breast cancer in African populations: a literature review.Global health, epidemiology and genomics · 2018Review
- Facilitating the Calculation of the Efficient Score Using Symbolic Computing.The American statistician · 2018Article
- Previous GWAS hits in relation to young-onset breast cancer.Breast cancer research and treatment · 2017Article
Corrections and comments
- Erratum issuedGreene, Mark I [corrected to Greene, Mark H]
- Erratum issuedEMBRACE [added]
Authors and funding
122 authors at 20 institutions in 14 countries.
Funding
Abstract
The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10(-5) and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, ) and for rs311499 was 0.72 (95% CI 0.61-0.85, ). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, ). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.