A non-synonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
Cancer Epidemiology, Biomarkers & Prevention, 06/26/2012
Ding YC et al. – The IRS1 Gly972Arg SNP, 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 2 mutation carriersMethods
- IRS1 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.
- Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 [Hazard ratio (HR) = 1.43; 95% 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 2 mutations than class 1 ( mutations (class 2 HR=1.86, 95% CI: 1.28-2.70; class 1 HR=0.86, 95%CI:0.69-1.09 ; p-for difference=0.0006).
- Rs13306465 was associated with ovarian cancer risk in BRCA1 class 2 mutation carriers (HR = 2.42; p = 0.03).