ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2012
A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2012. 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 17 papers, 3 of them syntheses that pooled it.
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Who cites it
17 citing papers in PubMed, 3 syntheses or guidelines pooled it, 23 citations in OpenAlex.
- XRCC3 Thr241Met polymorphism and ovarian cancer risk: a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
- Pooled it
- Association between insulin receptor substrate 1 Gly972Arg polymorphism and cancer risk.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Pooled it
- Review
- Insights into genetic modifiers of breast cancer risk in carriers of BRCA1 and BRCA2 pathogenic variants.Hereditary cancer in clinical practice · 2025Review
- The Intricate Crosstalk Between Insulin and Pancreatic Ductal Adenocarcinoma: A Review From Clinical to Molecular.Frontiers in cell and developmental biology · 2022Review
- Recent Advances in Integrative Multi-Omics Research in Breast and Ovarian Cancer.Journal of personalized medicine · 2021Review
- The RAD52 S346X variant reduces risk of developing breast cancer in carriers of pathogenic germline BRCA2 mutations.Molecular oncology · 2020Article
- Genetic Variants in the 3'UTR ofDiagnostics (Basel, Switzerland) · 2020Article
- PLAG1 silencing promotes cell chemosensitivity in ovarian cancer via the IGF2 signaling pathway.International journal of molecular medicine · 2020Article
- BRCA1 and BRCA2 5' noncoding region variants identified in breast cancer patients alter promoter activity and protein binding.Human mutation · 2018Article
- Common Genetic Variation and Breast Cancer Risk-Past, Present, and Future.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2018Review
- Association between IRS1 Gene Polymorphism and Autism Spectrum Disorder: A Pilot Case-Control Study in Korean Males.International journal of molecular sciences · 2016Article
- Identification of homogeneous and heterogeneous variables in pooled cohort studies.Biometrics · 2015Article
- Novel insulin receptor substrate 1 and 2 variants in breast and colorectal cancer.Oncology reports · 2013Article
- Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited disease.Human genetics · 2013Review
- mEH Tyr113His polymorphism and the risk of ovarian cancer development.Journal of ovarian research · 2013Article
Corrections and comments
- Erratum issued
Authors and funding
168 authors at 2 institutions in 4 countries.
Funding
Abstract
backgroundWe previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.
methodsIRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.
resultsRs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).
conclusionThe IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers. IMPACT: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
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