Research Division, National Cancer Institute, Rama VI Road, Ratchathewi, Bangkok, 10400, Thailand.
Breast Cancer Res Treat. 2010 Oct;123(3):885-93. doi: 10.1007/s10549-010-0804-4. Epub 2010 Feb 24.
Dietary folate as well as polymorphic variants in one-carbon metabolism genes may modulate risk of breast cancer through aberrant DNA methylation and altered nucleotide synthesis and repair. Alcohol is well recognized as a risk factor for breast cancer, and interactions with one-carbon metabolism has also been suggested. The purpose of this study is to test the hypothesis that genetic polymorphisms in the folate and alcohol metabolic pathway are associated with breast cancer risk. Twenty-seven single nucleotide polymorphisms (SNPs) in the MTR, MTRR, MTHFR, TYMS, ADH1C, ALDH2, GSTP1, NAT1, NAT2, CYP2E1 DRD2, DRD3, and SLC6A4 were genotyped. Five hundred and seventy patients with histopathogically confirmed breast cancer and 497 controls were included in the present study. Association of genotypes with breast cancer risk was evaluated using multivariate logistic regression to estimate odds ratios (OR) and their 95% confidence intervals (95% CI). Increased risk was observed for homozygotes at the MTR SNPs (rs1770449 and rs1050993) with the OR = 2.21 (95% CI 1.18-4.16) and OR = 2.24 (95% CI 1.19-4.22), respectively. A stratified analysis by menopausal status indicated the association between the NAT2 SNP (rs1799930) and breast cancer was mainly evident in premenopausal women (OR 2.70, 95% CI 1.20-6.07), while the MTRR SNP (rs162049) was significant in postmenopausal women (OR 1.61, 95% CI 1.07-2.44). Furthermore, SNPs of the genes that contribute to alcohol behavior, DRD3 (rs167770), DRD2 (rs10891556), and SLC6A4 (rs140701), were also associated with an increased risk of breast cancer. No gene-gene or gene-environment interactions were observed in this study. Our results suggest that genetic polymorphisms in folate and alcohol metabolic pathway influence the risk of breast cancer in Thai population.
膳食叶酸以及一碳代谢基因的多态性变异可能通过异常的 DNA 甲基化和核苷酸合成与修复改变，从而调节乳腺癌的风险。酒精已被明确认定为乳腺癌的风险因素，并且一碳代谢的相互作用也已被提出。本研究的目的是检验这样一个假设，即叶酸和酒精代谢途径中的遗传多态性与乳腺癌风险相关。在 MTR、MTRR、MTHFR、TYMS、ADH1C、ALDH2、GSTP1、NAT1、NAT2、CYP2E1、DRD2、DRD3 和 SLC6A4 中检测到 27 个单核苷酸多态性 (SNP)。本研究纳入了 570 名经组织病理学证实患有乳腺癌的患者和 497 名对照。使用多变量逻辑回归来估计比值比 (OR) 及其 95%置信区间 (95%CI)，评估基因型与乳腺癌风险的相关性。MTR 基因的 SNP(rs1770449 和 rs1050993)的纯合子与 OR=2.21(95%CI 1.18-4.16)和 OR=2.24(95%CI 1.19-4.22)的风险增加有关。按绝经状态进行分层分析表明，NAT2 基因的 SNP(rs1799930)与乳腺癌之间的相关性主要在绝经前妇女中明显(OR 2.70,95%CI 1.20-6.07)，而 MTRR 基因的 SNP(rs162049)在绝经后妇女中显著(OR 1.61,95%CI 1.07-2.44)。此外，对酒精行为有贡献的基因的 SNP，DRD3(rs167770)、DRD2(rs10891556)和 SLC6A4(rs140701)也与乳腺癌风险增加有关。本研究未观察到基因-基因或基因-环境相互作用。我们的研究结果表明，叶酸和酒精代谢途径中的遗传多态性影响泰国人群乳腺癌的风险。
