Plasma folate, methylenetetrahydrofolate reductase (MTHFR), and colorectal cancer risk in three large nested case-control studies
Plasma folate, methylenetetrahydrofolate reductase (MTHFR), and colorectal cancer risk in three large nested case-control studies
复制标题
DOI：
10.1007/s10552-012-9911-3
复制
发表时间：
2012-04-01
影响因子：
2.3
通讯作者：
Giovannucci, Edward
中科院分区：
文献类型：
--
作者：
Lee, Jung Eun;Wei, Esther K.;Giovannucci, Edward
很少有前瞻性研究探讨血液中叶酸水平与亚甲基四氢叶酸还原酶（MTHFR）多态性和结直肠癌之间的关系。我们在三项大型前瞻性研究中评估了血浆叶酸、MTHFR C677 T和A1298 C与结直肠癌之间的关系：护士健康研究、卫生专业人员随访研究和医生健康研究。共确定了602例事件病例，并与提供血液标本的对照组进行了单独匹配。我们使用条件Logistic回归计算相对风险（RR）和95%置信区间（95%CI），然后使用随机效应模型汇总估计值。我们发现，低血浆叶酸水平的参与者患结直肠癌的风险较低：与最低四分位数相比，血浆叶酸水平的每个依次升高的四分位数的RR（95%CI）分别为1.55（1.14-2.11）、1.37（1.00-1.88）和1.47（1.07-2.01;趋势P = 0.10）。对于MTHFR多态性，677 TT与CC/CT的RR（95%CI）为0.62（0.44-0.90），1298 CC与AC/AA的RR（95%CI）为0.68（0.31-1.51），这些低风险基因型与较低的循环血浆叶酸水平相关。当我们划分血浆叶酸水平的变化时，由于叶酸摄入引起的变化与结直肠癌风险不呈正相关。我们发现低血浆叶酸水平与结直肠癌的低风险相关。低血浆叶酸水平的结直肠癌风险较低的原因需要阐明，因为血浆叶酸水平可以反映饮食摄入，遗传影响和其他因素。
Few prospective studies have examined the associations between blood levels of folate, in conjunction with methylenetetrahydrofolate reductase (MTHFR) polymorphisms, and colorectal cancer. We evaluated the associations between plasma folate, MTHFR C677T, and A1298C, and colorectal cancer in three large prospective studies: the Nurses' Health Study, the Health Professionals Follow-up Study, and the Physicians' Health Study. A total of 602 incident cases were identified and individually matched to controls who provided blood specimens. We used conditional logistic regression to calculate the relative risk (RR) and 95% confidence interval (95% CI) and then pooled the estimates using a random effects model. We found a lower risk of colorectal cancer among participants with low plasma folate levels: compared with the lowest quartile, RRs (95% CIs) for each successively higher quartile of plasma folate levels were 1.55 (1.14-2.11), 1.37 (1.00-1.88), and 1.47 (1.07-2.01; P for trend = 0.10). For the MTHFR polymorphisms, RRs (95% CIs) were 0.62 (0.44-0.90) for 677TT versus CC/CT and 0.68 (0.31-1.51) for 1298CC versus AC/AA, and these lower-risk genotypes were associated with lower circulating plasma folate levels. When we partitioned the variation in plasma folate levels, variation due to folate intake was not positively associated with colorectal cancer risk. We found that low plasma folate levels were associated with lower risk of colorectal cancer. The reasons underlying a lower risk of colorectal cancer with low plasma folate levels require elucidation because plasma folate levels can reflect dietary intake, genetic influences, and other factors.