Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer:: A meta-analysis
Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer:: A meta-analysis
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DOI：
10.1053/j.gastro.2006.08.010
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发表时间：
2006-10-01
期刊：
影响因子：
29.4
通讯作者：
Wolk, Alicja
中科院分区：
文献类型：
--
作者：
Larsson, Susanna C.;Giovannucci, Edward;Wolk, Alicja
背景与目的：越来越多的证据表明，叶酸摄入不足和叶酸代谢受损可能与胃肠道肿瘤的发生有关。我们对叶酸代谢的中心酶S的叶酸摄入或基因多态性与食道癌、胃癌或胰腺癌风险的关系进行了系统的综述和荟萃分析。方法：应用MEDLINE检索2006年3月发表的研究文献。特定研究的相对风险通过其方差的倒数进行加权，以获得随机效应汇总估计。结果：食管鳞癌(4例对照)、食管腺癌(3例对照)和胰腺癌(1例对照，4个队列)的总相对危险度分别为0.66(9s%可信区间，0.53~0.83)、0.50(9s%CI，0.39~0.65)和0.49(95%CI，0.3s~0.67)。结果膳食叶酸摄入量与胃癌发病风险(9例对照，2例队列)不一致。在大多数研究中，MTHFR 677TT(变异)基因型与酶活性降低相关，与食道鳞状细胞癌、贲门腺癌、非贲门癌、胃癌(所有亚点)和胰腺癌的风险增加相关；22个优势比中除一个外，所有的优势比都是>；1，其中13个估计具有统计学意义。对亚甲基四氢叶酸还原酶A1298C基因多态性的研究有限且不一致。结论：这些发现支持叶酸可能在食道、胃和胰腺癌发生中起作用的假说。
Background & Aims: Increasing evidence suggests that a low folare intake and impaired folate metabolism may be implicated in the development of gastrointestinal cancers. We conducted a systematic review with meta-analysis of epidemiologic studies evaluating the association of folate intake or genetic polymorphisms in S,10-methylenetetrahydrofolate reductase (MTHFR), a central enzyme in folate metabolism, with risk of esophageal, gastric, or pancreatic cancer. Methods: A literature search was performed using MEDLINE for studies published through March 2006. Study-specific relative risks were weighted by the inverse of their variance to obtain random-effects summary estimates. Results: The summary relative risks for the highest versus the lowest category of dietary folate intake were 0.66 (9S% confidence interval [CI], 0.53-0.83) for esophageal squamous cell carcinoma (4 case-control), 0.50 (9S% CI, 0.39-0.65) for esophageal adenocarcinoma (3 casecontrol), and 0.49 (95% CI, 0.3S-0.67) for pancreatic cancer (I case-control, 4 cohort); there was no heterogeneity among studies. Results on dietary folate intake and risk of gastric cancer (9 case-control, 2 cohort) were inconsistent. In most studies, the MTHFR 677TT (variant) genotype, which is associated with reduced enzyme activity, was associated with an increased risk of esophageal squamous cell carcinoma, gastric cardia adenocarcinoma, noncardia gastric cancer, gastric cancer (all subsites), and pancreatic cancer; all but one of 22 odds ratios were > 1, of which 13 estimates were statistically significant. Studies of the MTHFR A1298C polymorphism were limited and inconsistent. Conclusions: These findings support the hypothesis that folare may play a role in carcinogenesis of the esophagus, stomach, and pancreas.