Dietary folate and related micronutrients, folate-metabolising genes, and ovarian cancer survival
Dietary folate and related micronutrients, folate-metabolising genes, and ovarian cancer survival
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DOI：
10.1016/j.ygyno.2013.12.025
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发表时间：
2014-03-01
影响因子：
4.7
通讯作者：
Nagle, C. M.
中科院分区：
文献类型：
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作者：
Dixon, S. C.;Ibiebele, T. I.;Nagle, C. M.
目标。叶酸对DNA合成和甲基化至关重要，并与肿瘤进展有关。很少有研究考察它在卵巢癌存活中的作用。我们的目的是确定叶酸摄入量、相关单碳营养素、叶酸代谢基因的单核苷酸多态性（snp）与卵巢癌诊断后生存之间的关系。该分析包括1270名2002-2006年诊断为浸润性上皮性卵巢癌的妇女。通过自我管理的问卷收集诊断前和诊断后的生活方式、饮食和社会人口统计信息。对DNA样品进行亚甲基四氢叶酸还原酶（MTHFR）、蛋氨酸合成酶（MTR）和蛋氨酸合成酶还原酶（MTRR）基因的snp分型。采用Cox回归计算校正风险比（hr）和95%置信区间（ci）。多变量分析没有发现诊断前叶酸、叶酸、维生素B2、B6和B12、蛋氨酸、甜菜碱或胆碱的高摄入量与总体生存率之间的关联。在分层分析中，较高的叶酸和叶酸摄入量与患有黏液性肿瘤的女性（hr / 100 μ g分别为1.30和1.43）和吸烟者（hr / 100 μ g分别为1.23和1.16）的生存率显著降低相关。研究还表明，诊断后补充更多叶酸与更差的生存率相关（HR / 100 μ g 1.03, 95%CI 1.00-1.05）。MTHFR SNP rs2066470与生存率显著相关（每等位基因HR 0.81, 95%CI 0.67-0.98）。我们的数据没有提供叶酸摄入影响卵巢癌存活的证据。然而，与吸烟的综合影响，以及黏液亚型和诊断后叶酸的发现，值得进一步调查。(C) 2014爱思唯尔公司版权所有。
Objective. Folate is essential for DNA synthesis and methylation and is implicated in tumour progression. Few studies have examined its role in ovarian cancer survival. Our objective was to determine relationships between intake of folate, related one-carbon nutrients, single nucleotide polymorphisms (SNPs) in folate-metabolising genes and survival following ovarian cancer diagnosis.Methods. This analysis included 1270 women with invasive epithelial ovarian cancer diagnosed in 2002-2006. Pre-diagnostic and some post-diagnostic lifestyle, dietary, and sociodemographic information was collected via self-administered questionnaires. DNA samples were genotyped for SNPs in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and methionine synthase reductase (MTRR) genes. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression.Results. Multivariate analyses did not identify associations between higher pre-diagnostic intake of folate, folic acid, vitamins B2, B6, and B12, methionine, betaine or choline and survival overall. In stratified analyses, higher folic acid and folate intake was associated with significantly worse survival among women with mucinous tumours (HRs per 100 mu g 1.30 and 1.43, respectively) and smokers (HRs per 100 mu g 1.23 and 1.16 respectively). There was also a suggestion that higher supplemental folic acid use post-diagnosis was associated with worse survival (HR per 100 mu g 1.03, 95%CI 1.00-1.05). MTHFR SNP rs2066470 was significantly associated with survival (per allele HR 0.81, 95%CI 0.67-0.98).Conclusions. Our data provide little evidence that folate intake affects ovarian cancer survival. However, combined effects with smoking, and findings within the mucinous subtype and for post-diagnosis folic acid, warrant further investigation. (C) 2014 Elsevier Inc. All rights reserved.