Division of Medical Sciences, National Cancer Centre, Singapore, 11 Hospital Drive, Singapore, Republic of Singapore.
Breast Cancer Res Treat. 2012 Nov;136(1):209-20. doi: 10.1007/s10549-012-2234-y. Epub 2012 Sep 11.
Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations, and thus GWAS-identified single nucleotide polymorphisms (SNPs) in one population may not be of significance in another population. In order to explore the role of breast cancer susceptibility variants in a Chinese population of Southern Chinese descent, we analyzed 22 SNPs for 1,191 breast cancer cases and 1,534 female controls. Associations between the SNPs and clinicopathological features were also investigated. In addition, we evaluated the combined effects of associated SNPs by constructing risk models. Eight SNPs were associated with an elevated breast cancer risk. Rs2046210/6q25.1 increased breast cancer risk via an additive model [per-allele odds ratio (OR) = 1.43, 95 % confidence interval (CI) = 1.26-1.62], and was associated with estrogen receptor (ER)-positive (per-allele OR = 1.39, 95 % CI = 1.20-1.61) and ER-negative (per-allele OR = 1.55, 95 % CI = 1.28-1.89) disease. Rs2046210 was also associated with stage 1, stage 2, and stage 3 disease, with per-allele ORs of 1.38 (1.14-1.68), 1.48 (1.25-1.74), and 1.58 (1.28-1.94), respectively. Four SNPs mapped to 10q26.13/FGFR2 were associated with increased breast cancer risk via an additive model with per-allelic risks (95 % CI) of 1.26 (1.12-1.43) at rs1219648, 1.22 (1.07-1.38) at rs2981582, 1.21 (1.07-1.36) at rs2981579, and 1.18 (1.04-1.35) at rs11200014. Variants of rs7696175/TLR1, TLR6, rs13281615/8q24, and rs16886165/MAP3K1 were also associated with increased breast cancer risk, with per-allele ORs (95 % CI) of 1.16 (1.00-1.34), 1.15 (1.02-1.29), and 1.15 (1.01-1.29), respectively. Five SNPs associated with breast cancer risk predominantly among ER-positive tumors (rs2981582/FGFR2, rs4415084/MRPS30, rs1219648/FGFR2, rs2981579/FGFR2, and rs11200014/FGFR2). Among our Chinese population, the risk of developing breast cancer increased by 90 % for those with a combination of 6 or more risk alleles, compared to patients with ≤3 risk alleles.
全基因组关联研究（GWAS）主要基于欧洲血统人群，确定了各种乳腺癌遗传易感性位点。欧洲和亚洲人群之间存在不同的连锁不平衡模式，因此在一个人群中确定的单核苷酸多态性（SNP）在另一个人群中可能没有意义。为了探讨乳腺癌易感性变异在中国南方汉族人群中的作用，我们分析了 22 个 SNP 在 1191 例乳腺癌病例和 1534 名女性对照中的作用。还研究了 SNP 与临床病理特征之间的关系。此外，我们通过构建风险模型评估了相关 SNP 的联合作用。有 8 个 SNP 与乳腺癌风险升高相关。rs2046210/6q25.1 通过加性模型增加乳腺癌风险[每个等位基因的优势比（OR）=1.43，95%置信区间（CI）=1.26-1.62]，与雌激素受体（ER）阳性（每个等位基因的 OR=1.39，95%CI=1.20-1.61）和 ER 阴性（每个等位基因的 OR=1.55，95%CI=1.28-1.89）疾病相关。rs2046210 还与 1 期、2 期和 3 期疾病相关，每个等位基因的 OR 分别为 1.38（1.14-1.68）、1.48（1.25-1.74）和 1.58（1.28-1.94）。四个 SNP 映射到 10q26.13/FGFR2，通过加性模型与每个等位基因的风险（95%CI）为 1.26（1.12-1.43）在 rs1219648、1.22（1.07-1.38）在 rs2981582、1.21（1.07-1.36）在 rs2981579 和 1.18（1.04-1.35）在 rs11200014。rs7696175/TLR1、TLR6、rs13281615/8q24 和 rs16886165/MAP3K1 的变体也与乳腺癌风险增加相关，每个等位基因的 OR（95%CI）分别为 1.16（1.00-1.34）、1.15（1.02-1.29）和 1.15（1.01-1.29）。五个 SNP 主要与 ER 阳性肿瘤相关（rs2981582/FGFR2、rs4415084/MRPS30、rs1219648/FGFR2、rs2981579/FGFR2 和 rs11200014/FGFR2）。在我们的中国人群中，与携带≤3 个风险等位基因的患者相比，携带 6 个或更多风险等位基因的患者患乳腺癌的风险增加了 90%。
