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

被引:102
作者
Lewis, Sarah J. [1 ]
Harbord, Roger M. [1 ]
Harris, Ross [1 ]
Smith, George Davey [1 ]
机构
[1] Univ Bristol, Dept Social Med, Bristol BS8 2PR, Avon, England
来源
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2006年 / 98卷 / 22期
关键词
D O I
10.1093/jnci/djj440
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1607 / 1622
页数:16
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