New Breast Cancer Risk Variant Discovered at 10q25 in East Asian Women
Menée en Chine et en Corée à partir des données de deux études d'association sur le génome entier incluant au total 5 083 patientes atteintes d'un cancer du sein et 4 376 témoins, puis menée sur 7 294 autres cas et 9 404 témoins, cette étude identifie, sur la région chromosomique 10q25, un nouveau variant génétique associé au risque de cancer du sein chez les femmes d'Asie orientale
Background : Recently, 41 new genetic susceptibility loci for breast cancer risk were identified in a genome-wide association study conducted in European descendants. Most of these risk variants have not been directly replicated in Asian populations. Methods : We evaluated nine of those non-replication loci in East Asians in order to identify new risk variants for breast cancer in these regions. First, we analyzed single nucleotide polymorphisms (SNPs) in these regions using data from two GWAS conducted among Chinese and Korean women, including 5,083 cases and 4,376 controls (Stage 1). In each region we selected a SNP showing the strongest association with breast cancer risk for replication in an independent set of 7,294 cases and 9,404 controls of East Asian descents (Stage 2). Logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) as a measure of the association of breast cancer risk and genetic variants. Results : Two SNPs were replicated in Stage 2 at P < 0.05: rs1419026 at 6q14 (per allele OR = 1.07, 95% CI: 1.03-1.12, P = 3.0×10-4) and rs941827 at 10q25 (OR = 0.92, 95% CI: 0.89-0.96, P = 5.3×10-5). The association with rs941827 remained highly statistically significant after adjusting for the risk variant identified initially in women of European ancestry (OR = 0.88, 95% CI: 0.82-0.97, P = 5.3×10-5). Conclusions : We identified a new breast cancer risk variant at 10q25 in East Asian women. Impact : Results from this study improve the understanding of the genetic basis for breast cancer.