Human Genetics Unit, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo 8, Sri Lanka.
Center for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, MD, USA.
BMC Cancer. 2018 Feb 13;18(1):180. doi: 10.1186/s12885-018-4112-4.
While a range of common genetic variants have been identified to be associated with risk of sporadic breast cancer in several Western studies, little is known about their role in South Asian populations. Our objective was to examine the association between common genetic variants in breast cancer related genes and risk of breast cancer in a cohort of Sri Lankan women.
A case-control study of 350 postmenopausal women with breast cancer and 350 healthy postmenopausal women was conducted. Genotyping using the iPLEX GOLD assay was done for 56 haplotype-tagging single nucleotide polymorphisms (SNPs) in 36 breast cancer related genes. Testing for association was done using an additive genetic model. Odds ratios and 95% confidence intervals were calculated using adjusted logistic regression models.
Four SNPs [rs3218550 (XRCC2), rs6917 (PHB), rs1801516 (ATM), and rs13689 (CDH1)] were significantly associated with risk of breast cancer. The rs3218550 T allele and rs6917 A allele increased breast cancer risk by 1.5-fold and 1.4-fold, respectively. The CTC haplotype defined by the SNPs rs3218552|rs3218550|rs3218536 on chromosome 7 (P = 0.0088) and the CA haplotype defined by the SNPs rs1049620|rs6917 on chromosome 17 (P = 0.0067) were significantly associated with increased risk of breast cancer. The rs1801516 A allele and the rs13689 C allele decreased breast cancer risk by 0.6-fold and 0.7-fold, respectively.
These findings suggest that common genetic polymorphisms in the XRCC2, PHB, CDH1 and ATM genes are associated with risk of breast cancer among Sri Lankan postmenopausal women. The exact biological mechanisms of how these variants regulate overall breast cancer risk need further evaluation using functional studies.
虽然在几项西方研究中已经确定了一系列常见的遗传变异与散发型乳腺癌的风险相关，但对于南亚人群中的这些遗传变异的作用知之甚少。我们的目的是研究乳腺癌相关基因中的常见遗传变异与斯里兰卡女性乳腺癌风险之间的关系。
对 350 名绝经后患有乳腺癌的女性和 350 名健康的绝经后女性进行了病例对照研究。使用 iPLEX GOLD 检测方法对 36 个乳腺癌相关基因中的 56 个单核苷酸多态性（SNP）进行了基因分型。使用加性遗传模型进行关联检验。使用调整后的逻辑回归模型计算比值比和 95%置信区间。
有 4 个 SNP [rs3218550（XRCC2）、rs6917（PHB）、rs1801516（ATM）和 rs13689（CDH1）]与乳腺癌风险显著相关。rs3218550 的 T 等位基因和 rs6917 的 A 等位基因使乳腺癌风险分别增加了 1.5 倍和 1.4 倍。位于染色体 7 上的 SNP rs3218552|rs3218550|rs3218536 定义的 CTC 单倍型（P=0.0088）和位于染色体 17 上的 SNP rs1049620|rs6917 定义的 CA 单倍型（P=0.0067）与乳腺癌风险增加显著相关。rs1801516 的 A 等位基因和 rs13689 的 C 等位基因使乳腺癌风险分别降低了 0.6 倍和 0.7 倍。
这些发现表明，XRCC2、PHB、CDH1 和 ATM 基因中的常见遗传多态性与斯里兰卡绝经后女性的乳腺癌风险相关。这些变异如何调节整体乳腺癌风险的确切生物学机制需要进一步通过功能研究进行评估。
