叶酸摄入量或水平与乳腺癌风险的观察性研究和基因关联研究的荟萃分析。

Meta-analyses of observational and genetic association studies of folate intakes or levels and breast cancer risk.

作者信息

Lewis Sarah J, Harbord Roger M, Harris Ross, Smith George Davey

机构信息

Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK.

出版信息

J Natl Cancer Inst. 2006 Nov 15;98(22):1607-22. doi: 10.1093/jnci/djj440.

DOI:10.1093/jnci/djj440

PMID:17105984

Abstract

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-microg/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-microg/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.

摘要

背景

病例对照研究的证据表明，增加膳食叶酸摄入量与降低乳腺癌风险相关。然而，大型队列研究未发现此类关联，且动物研究表明补充叶酸可能促进肿瘤发生。我们进行了一项荟萃分析，以总结关于此问题的观察性研究的现有证据，并对叶酸代谢关键酶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联进行荟萃分析。

方法

我们检索了截至2006年5月31日发表的Medline和ISI Web of Knowledge数据库中的相关研究。对于病例对照研究，我们使用随机效应分析计算叶酸摄入量每增加100微克/天的比值比（OR）；对于队列研究，计算相对风险（RR）。基于已发表的基因型频率，对MTHFR基因型研究计算未调整的比值比。

结果

共有13项病例对照研究和9项队列研究纳入了叶酸摄入量与乳腺癌风险的荟萃分析。对于叶酸摄入量每增加100微克/天，我们从病例对照研究中得出的汇总OR为0.91（95%置信区间[CI]=0.87至0.96），从队列研究中得出的汇总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。病例对照研究和队列研究可能存在测量误差、混杂因素，以及亚组分析可能产生的虚假关联；此外，病例对照研究可能存在回忆偏倚和发表偏倚。17项研究纳入了MTHFR C677T基因型与乳腺癌风险的荟萃分析。我们发现MTHFR 677 TT纯合子与CC纯合子之间的乳腺癌风险无差异（OR = 1.05，95%CI = 0.88至1.25），且没有证据表明叶酸摄入量与MTHFR基因型在乳腺癌风险上存在相互作用。