Meta-analyses of observational and genetic association studies of folate intakes or levels and breast cancer risk
Meta-analyses of observational and genetic association studies of folate intakes or levels and breast cancer risk
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DOI：
10.1093/jnci/djj440
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发表时间：
2006-11-15
影响因子：
10.3
通讯作者：
Smith, George Davey
中科院分区：
文献类型：
--
作者：
Lewis, Sarah J.;Harbord, Roger M.;Smith, George Davey
背景。病例对照研究的证据表明，饮食中叶酸摄入量的增加与乳腺癌风险的降低有关。然而，大型队列研究没有发现这种关联，动物研究表明叶酸补充剂可能促进肿瘤发生。我们进行了一项荟萃分析，总结了关于这一问题的观察性研究的现有证据，并对叶酸代谢的关键酶5,10-亚甲基四氢叶酸还原酶（MTHFR）基因的常见多态性与乳腺癌风险之间的关系进行了荟萃分析。方法：我们检索Medline和ISI Web of Knowledge数据库，检索截至2006年5月31日发表的相关研究。我们使用随机效应分析来计算病例对照研究的优势比（ORs）或队列研究中叶酸摄入量增加100 μ g/d的相对风险（rr）。根据已发表的基因型频率计算MTHFR基因型研究的未调整优势比。结果：叶酸摄入与乳腺癌风险的荟萃分析共纳入了13项病例对照研究和9项队列研究。我们发现病例对照研究的总体OR为0.91(95%可信区间[CI] = 0.87至0.96)，队列研究中叶酸摄入量增加100 μ g/d的总体RR为0.99 （95% CI = 0.98至1.01）。我们发现有证据表明病例对照研究可能存在严重的发表偏倚。病例对照和队列研究可能存在测量误差、混淆和可能由亚组分析引起的虚假关联；此外，病例对照研究可能存在回忆偏倚和发表偏倚。17项研究被纳入MTHFR C677T基因型与乳腺癌风险的荟萃分析。我们发现MTHFR 677 TT纯合子和CC纯合子的乳腺癌风险没有差异（OR = 1.05, 95% CI = 0.88至1.25），并且没有证据表明叶酸摄入量和MTHFR基因型对乳腺癌风险有相互作用。结论：饮食中叶酸摄入量的缺乏与乳腺癌的风险无关。
Background. Evidence from case-control studies suggests that increasing dietary folate intake is associated with a reduced risk of breast cancer. However, large cohort studies have found no such association, and animal studies suggest that folate supplementation may promote tumorigenesis. We conducted a meta-analysis to summarize the available evidence from observational studies on this issue and a meta-analysis of the association between a common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, a key enzyme in folate metabolism, and breast cancer risk. Methods: We searched Medline and ISI Web of Knowledge databases for relevant studies that were published through May 31, 2006. We used random-effects analysis to calculate odds ratios (ORs) for case-control studies or relative risks (RRs) for cohort studies for a 100-mu g/d increase in folate intake. Unadjusted odds ratios were calculated for the studies of MTHFR genotype based on published genotype frequencies. Results: A total of 13 case-control studies and nine cohort studies were included in the meta-analysis of folate intake and breast cancer risk. We found a summary OR of 0.91 (95% confidence interval [CI] = 0.87 to 0.96) from the case-control studies and a summary RR of 0.99 (95% CI = 0.98 to 1.01) from the cohort studies for a 100-mu g/d increase in folate intake. We found evidence that the case-control studies may have suffered from substantial publication bias. The case-control and cohort studies may have been subject to measurement error, confounding, and possibly spurious associations arising from subgroup analyses; in addition, the case-control studies were potentially subject to recall bias and publication bias. Seventeen studies were included in the meta-analysis of MTHFR C677T genotype and breast cancer risk. We found no difference in breast cancer risk between MTHFR 677 TT homozygotes and CC homozygotes (OR = 1.05, 95% CI = 0.88 to 1.25), and there was no evidence of an interaction between folate intake and MTHFR genotype on breast cancer risk. Conclusion: A lack of dietary folate intake is not associated with the risk of breast cancer.