Son Byung Ho, Kim Mi Kyung, Yun Young Mi, Kim Hee Jeong, Yu Jong Han, Ko Beom Seok, Kim Hanna, Ahn Sei Hyun
Department of Surgery, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Korea.
J Cancer Res Clin Oncol. 2015 Apr;141(4):633-45. doi: 10.1007/s00432-014-1849-2. Epub 2014 Oct 17.
We performed a case-control study to evaluate the association of genetic polymorphisms of estrogen-metabolizing enzyme genes and estrogen receptor genes with breast cancer risk according to age group and subtypes in Korean women.
Breast cancer patients (n = 830) and the hospital healthy controls (n = 390) with both clinical information and SNP data were included in the study. Age was divided into three groups: premenopausal under 35 years (n = 64), premenopausal over 35 years (n = 456), and postmenopausal women (n = 310), respectively. Tumor subtype was classified into four subtypes: luminal A, luminal B, HER2-overexpressing, and triple-negative, respectively. Genotyping of the selected SNPs in ESR1, ESR2, CYP1A1, CYP1B1, and COMT was conducted using the VeraCode Golden Gate Genotyping Assay Technology. Multiple logistic regression models (dominant, recessive, and additive) were applied to determine the odds ratio, 95% confidence interval, and p value.
ESR1, rs2881766, rs2077647, rs926778, and rs2273206 polymorphisms increased breast cancer risk, and rs3798377 decreased the risk in overall patients. The association between SNP genotype and breast cancer risk was varied according to age groups and tumor subtypes. For age subgroups, rs2881766 increased breast cancer risk in the all three age groups, and rs926778 increased the risk in premenopausal over 35 years women and in postmenopausal women. For the tumor subtypes, rs2881766 increased breast cancer risk manly in luminal A, HER2-overexpressing, and triple-negative subtypes except for luminal B subtype, and rs926778 increased the risk in luminal A and triple-negative subtypes. Rs3798577 decreased the risk in luminal B and triple-negative subtypes.
The results showed that ESR1 rs2881766 polymorphism increased breast cancer risk and rs3798377 decreased the risk in Korean women. Because of wide variation of the association between SNP genotype and breast cancer risk according to age group and tumor subtypes, further studies such as a large-scale cohort study need for validation and test of biologic significance.
我们开展了一项病例对照研究，以评估雌激素代谢酶基因和雌激素受体基因的基因多态性与韩国女性乳腺癌风险之间按年龄组和亚型划分的关联。
本研究纳入了有临床信息和单核苷酸多态性（SNP）数据的乳腺癌患者（n = 830）和医院健康对照者（n = 390）。年龄分为三组：35岁以下绝经前女性（n = 64）、35岁以上绝经前女性（n = 456）和绝经后女性（n = 310）。肿瘤亚型分为四种：管腔A型、管腔B型、人表皮生长因子受体2（HER2）过表达型和三阴性。使用VeraCode金标准基因分型检测技术对雌激素受体1（ESR1）、雌激素受体2（ESR2）、细胞色素P450 1A1（CYP1A1）、细胞色素P450 1B1（CYP1B1）和儿茶酚-O-甲基转移酶（COMT）中选定的SNP进行基因分型。应用多个逻辑回归模型（显性、隐性和加性）来确定比值比、95%置信区间和p值。
ESR1的rs2881766、rs2077647、rs926778和rs2273206多态性增加了总体患者的乳腺癌风险，而rs3798377降低了风险。SNP基因型与乳腺癌风险之间的关联因年龄组和肿瘤亚型而异。对于年龄亚组，rs2881766在所有三个年龄组中均增加乳腺癌风险，rs926778在35岁以上绝经前女性和绝经后女性中增加风险。对于肿瘤亚型，rs2881766主要在管腔A型、HER2过表达型和三阴性亚型（管腔B型除外）中增加乳腺癌风险，rs926778在管腔A型和三阴性亚型中增加风险。rs3798577在管腔B型和三阴性亚型中降低风险。
结果表明，ESR1的rs2881766多态性增加了韩国女性的乳腺癌风险，而rs3798377降低了风险。由于SNP基因型与乳腺癌风险之间的关联因年龄组和肿瘤亚型存在广泛差异，需要进一步开展大规模队列研究等研究来验证并测试生物学意义。
