Identification of novel susceptibility markers for the risk of overall breast cancer as well as subtypes defined by hormone receptor status in the Chinese population

Genome-wide association studies (GWAS) have identified common variants associated with breast cancer (BC) risk at multiple genetic loci. Above all, accumulated evidence suggests that inherited risk variants may vary in BC subtypes defined by estrogen receptor (ER) or progesterone receptor (PR) status. However, the underlying susceptibility of some variants for BC subtypes has not been well investigated in the Chinese population. Our objective was to explore the association among 23 GWAS-identified single-nucleotide polymorphisms (SNPs) and overall BC incidence, as well as its subtypes, in Chinese women. An extensive association analysis using the Sequenom MassARRAY (R) platform was conducted in a case-control study, including 551 BC patients and 577 healthy controls. Using the chi-squared (chi(2)) test and genetic model analysis, we found an association with BC for four SNPs (rs616488 (1p36.22/PEX14), rs6678914 (1q32.1/LGR6), rs17530068 (6q14/unknown) and rs6001930 (22q13.1/MKL1)) at a 5% level. Stratified analyses under this genetic model determined that rs616488 and rs6001930 were specific to ER positive and PR positive, rs17530068 was specific to ER positive and PR negative, rs3817198 (11p15.5/LSP1) was specific to ER negative and rs4784227 (16q12.1/CASC16) was specific to PR positive. Our study provides powerful new evidence for the relationship between SNPs and BC susceptibility.