Five Polymorphisms and Breast Cancer Risk: Results from the Breast Cancer Association Consortium

Abstract

Previous studies have suggested that minor alleles for ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 may influence breast cancer risk, but the evidence is inconclusive due to their small sample size. These polymorphisms were genotyped in more than 30,000 breast cancer cases and 30,000 controls, primarily of European descent, from 30 studies in the Breast Cancer Association Consortium. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) as a measure of association. We found that the minor alleles for these polymorphisms were not related to invasive breast cancer risk overall in women of European descent: ECCR4 per-allele OR (95% CI) = 0.99 (0.97-1.02), minor allele frequency = 27.5%; TNF 1.00 (0.95-1.06), 5.0%; CASP10 1.02 (0.98-1.07), 6.5%; PGR 1.02 (0.99-1.06), 15.3%; and BID 0.98 (0.86-1.12), 1.7%. However, we observed significant between-study heterogeneity for associations with risk for single-nucleotide polymorphisms (SNP) in CASP10, PGR, and BID. Estimates were imprecise for women of Asian and African descent due to small numbers and lower minor allele frequencies (with the exception of BID SNP). The ORs for each copy of the minor allele were not significantly different by estrogen or progesterone receptor status, nor were any significant interactions found between the polymorphisms and age or family history of breast cancer. In conclusion, our data provide persuasive evidence against an overall association between invasive breast cancer risk and ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 genotypes among women of European descent. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1610 -6)

Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA)

“…Several sensitivity analyses were performed (see Materials and Methods) but results did not change substantially and so those from the main analysis are presented in this report. Subsequent to the initiation of this study, a study from the Breast Cancer Association Consortium (BCAC), performed in 430 000 breast cancer cases and 30 000 controls has now found no evidence for an association of rs744154 with breast cancer risk in the general population (Gaudet et al, 2009). This is consistent with the lack of association found for BRCA1 and BRCA2 mutation carriers.…”

Association between the TNF-α-238G>A and TGF-β1 L10P Polymorphisms and Breast Cancer Risk: A Meta-Analysis

“…For TNF-a-238G>A, 3 studies, comprising 4 data sets with 35,578 cases and 38,095 controls, were identified for analyzing its connection with breast cancer susceptibility. Similarly, the cohort data from Gaudet et al [6] can be divided into 2 subsets based on ethnicity, which will be evaluated further (tables 1 and 2).…”

“…Our results suggested that the influence of the individual data sets on OR estimation was significant. The cohort data from Gaudet et al [6] is the most influential ( fig. 2).…”

Association of CASP9, CASP10 gene polymorphisms and tea drinking with colorectal cancer risk in the Han Chinese population

“…Li et al (2008) and Frank et al (2006) evaluated CASP10 rs13006529 polymorphism on the risk of cutaneous melanoma and familial breast cancer, with neither of the results reaching statistical significance. In the breast cancer, rs13010627 of CASP10 was found to be associated with a decreased risk (OR AA+AG : 0.62, 95% CI: 0.43-0.88) (Frank et al, 2006); however, this conclusion failed to remain significant in a subsequent large-scale pooled analysis (OR AA : 0.94, 95% CI: 0.72-1.22; OR AG : 1.03, 95% CI: 0.98-1.09) (Gaudet et al, 2009). Oh et al (2010) showed that CASP10 polymorphism increased the risk of CRC.…”