Methylation and Oxidation in Breast Cancer Epidemiology

描述(由申请人提供)：有相当大的流行病学 有证据表明饮酒与罹患乳腺癌的风险有关 摄入蔬菜和水果可能会降低患病风险。利用现有案例 对照研究，我们建议检查两种致病机制，一种是碳 代谢和/或氧化应激与乳腺癌。我们的首要目标是 检查与单碳代谢相关的元素与风险的关系。我们 建议a)研究一碳中重要的酶的遗传变异 代谢(亚甲基四氢叶酸还原酶(MTHFR)、蛋氨酸合成酶 (MS)和胱硫酮B-合酶(CBS))与风险的关系并进行调查 这些遗传因素与膳食叶酸和酒精的相互作用 乳腺癌风险；b)调查饮食中的叶酸与 酒精和这些遗传因素与总的p53突变和特殊的 P53突变和c)研究膳食叶酸与 酒精和这些遗传因素伴随着p16基因的高甲基化， 乳腺肿瘤中BRCA1基因和雌激素受体基因的表达我们的第二个目标是 检查与氧化应激有关的元素和有风险的抗氧化剂。我们 建议a)检查一种重要酶的遗传变异的关系 在控制氧化平衡中(锰超氧化物歧化酶) 并研究这种遗传因素与饮食因素的相互作用 氧化剂和抗氧化剂；以及b)研究两者之间的联系 氧化剂和抗氧化剂的饮食来源与总的和特定的P53 突变。通过结合摄入量、遗传易感性和肿瘤的信息 特征，就有可能对这一角色做出更清晰的推断 在乳腺癌病因学中的这两种机制中，潜在的重要 对公共健康的影响。

DESCRIPTION (provided by applicant): There is considerable epidemiologic evidence that alcohol intake is related to risk of breast cancer and that intake of vegetables and fruits may reduce risk. Utilizing an existing case control study, we propose to examine two etiological mechanisms, one-carbon metabolism and/or oxidative stress and breast cancer. Our first aim is to examine the relation of elements related to one-carbon metabolism with risk. We propose a) to investigate genetic variation in enzymes important in one-carbon metabolism (methylene tetrahydrofolate reductase (MTHFR), methionine synthase (MS) and cystathione B-synthase (CBS)) in relation to risk and to investigate interaction of these genetic factors with dietary folate and alcohol with breast cancer risk; b) to investigate the association of dietary folate and alcohol and these genetic factors with total p53 mutations and with particular p53 mutations and c) to investigate the association of dietary folate and alcohol and these genetic factors with hypermethylation of the p16 gene, the BRCA1 gene and the estrogen receptor gene in breast tumors. Our second aim is to examine elements related to oxidative stress and antioxidants with risk. We propose to a) examine the relation of genetic variation in an enzyme important in the control of oxidative balance (manganese superoxide dismutase (MnSOD)) and to examine interactions of this genetic factor with dietary factors both oxidants and antioxidants; and b) to investigate the association between dietary sources of oxidants and antioxidants with total and particular p53 mutations. By combining information on intake, genetic susceptibility and tumor characteristics, it will be possible to make clearer inferences about the role of these two mechanisms in breast cancer etiology, with potentially important public health implications.