One-carbon metabolism-related gene polymorphisms and risk of breast cancer
One-carbon metabolism-related gene polymorphisms and risk of breast cancer
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DOI：
10.1093/carcin/bgm295
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发表时间：
2008-02-01
期刊：
影响因子：
4.7
通讯作者：
Tajima, Kazuo
中科院分区：
文献类型：
--
作者：
Suzuki, Takeshi;Matsuo, Keitaro;Tajima, Kazuo
日本人群的环境暴露和/或遗传背景可能导致日本乳腺癌发病率相对较低，但尚未详细阐明。叶酸在DNA甲基化和合成中起着重要作用，因此可能参与乳腺癌的发展。编码一碳代谢酶亚甲基四氢叶酸还原酶（MTHFR C677 T）、甲硫氨酸合成酶（MTR A2756 G）、甲硫氨酸合成酶还原酶（MTRR A66 G）和胸苷酸合成酶（TS）的基因的功能多态性影响叶酸代谢，但流行病学研究得出了不一致的结果。因此，我们进行了一项病例对照研究，以澄清它们与乳腺癌风险的关系。共有456例乳腺癌病例和912例年龄匹配和绝经状态匹配的非癌症对照进行了多态性基因分型。采用调整潜在混杂因素的条件Logistic模型估计比值比（OR）和95%置信区间（CI），并评估多态性与叶酸摄入量之间的基因-环境相互作用。我们通过基于绝经状态的分析观察到MTHFR 677 TT基因型的绝经后乳腺癌风险增加（OR = 1.83，95%CI：1.08-3.11）。联合分析发现，MTHFR 677 TT基因型和膳食叶酸摄入量低的绝经后妇女与677 CC基因型和叶酸摄入量充足的绝经后妇女相比，其OR显著升高（OR = 2.80，95%CI：1.11-7.07）。此外，MTRR A66 G多态性和叶酸摄入量之间的相互作用绝经后乳腺癌的风险进行了观察（交互作用P = 0.008）。我们的研究结果表明，MTHFR和MTRR基因多态性与绝经后妇女乳腺癌的个体易感性相关。
Environmental exposures and/or genetic background in Japanese population, which might contribute to the relatively low breast cancer incidence rates in Japan, have not been clarified in detail. Folate plays an essential role in DNA methylation and synthesis, and thus may be involved in the development of breast cancer. Functional polymorphisms in genes encoding one-carbon metabolism enzymes, methylenetetrahydrofolate reductase (MTHFR C677T), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G) and thymidylate synthase (TS), influence folate metabolism, but epidemiological studies have yielded inconsistent findings. We therefore conducted a case-control study to clarify their associations with breast cancer risk. A total of 456 breast cancer cases and 912 age-matched and menopausal status-matched non-cancer controls were genotyped for the polymorphisms. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional logistic models adjusted for potential confounders and gene-environment interactions between the polymorphisms and folate consumption were also evaluated. We observed an increased risk of postmenopausal breast cancer with the MTHFR 677TT genotype (OR = 1.83, 95% CI: 1.08-3.11) with a menopausal status-based analysis. In combination analysis, a significantly elevated OR was found among postmenopausal women with the MTHFR 677TT genotype and lower intake of dietary folate compared with those with 677CC genotype and adequate folate consumption (OR = 2.80, 95% CI: 1.11-7.07). In addition, interaction between the MTRR A66G polymorphism and folate intake for risk of postmenopausal breast cancer was observed (interaction P = 0.008). Our findings indicated that the MTHFR and MTRR polymorphisms were associated with individual susceptibility to breast cancer among postmenopausal women.