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.

Figure 1

Per-allele ORs and 95% CIs for breast cancer risk by study are shown for ERCC4 rs744154 (A), TNF rs361525 (B), CASP10 rs13010627 (C), PGR rs1042838 (D), and BID rs8190315 (E), based on data from ~30,000 cases and 30,000 controls from the Breast Cancer Association Consortium. Studies are weighted and ranked according to the inverse of the variance of the log OR estimate. The size of the box is inversely proportional to the variance of the log OR estimate. The solid line is drawn where OR is equal to 1.0, and the dotted line is at the OR estimate for all studies combined. Estimates were calculated separately for women of European, Asian (labeled as “Asian”), and African (labeled as “AA”) descent. Study acronyms are defined in Supplementary Table S1.