Background

Studies disagree as to whether intakes of folate-mediated one-carbon metabolism nutrients are associated with endometrial cancer.

Methods

Using data from the large, prospective NIH-AARP Diet and Health Study, we used Cox proportional hazards models to evaluate endometrial cancer risk associated with calorie-adjusted dietary intake of several B vitamins and methionine. All models accounted for age, race, body mass index (BMI), smoking, oral-contraceptive use, menopausal hormone therapy use and caloric intake. We estimated associations by time from baseline (≤3 or >3 years) and stratified models by BMI (<25 or ≥25 kg/m²). During 16 years of follow-up, we identified 2329 endometrial cancer cases among 114 414 participants.

Results

After adjustment for confounding, we observed increased risk for endometrial cancer with greater consumption of dietary total folate, natural folate, B2, B6 and B12 [hazard ratios (HRs) ranging from 1.14 to 1.24 for the highest quintile (Q5) vs the lowest (Q1)]. Higher intakes of total folate, natural folate, B6 and B12 continued to be associated with increased risk when limiting follow-up to >3 years from baseline. We observed risks for the highest intakes of B2 [Q5 vs Q1: HR 1.27 95% confidence interval (CI) 1.07–1.50], B12 (Q5 vs Q1: HR 1.38 CI 1.17–1.63) and methionine (Q5 vs Q1: HR 1.26 CI 1.07–1.48) among women who were overweight/obese, but not among normal/underweight women.

Conclusions

Our findings indicate that one-carbon metabolism plays a role in endometrial carcinogenesis and exploration of this role in tissue and cellular biology studies is warranted.

中文翻译：

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饮食中叶酸介导的一碳代谢所涉及的营养摄入和子宫内膜癌的风险

背景

关于叶酸介导的一碳代谢营养素的摄入是否与子宫内膜癌有关，研究存在分歧。

方法

使用来自大型，前瞻性NIH-AARP饮食与健康研究的数据，我们使用Cox比例风险模型来评估与热量调整饮食中摄入的几种B维生素和蛋氨酸相关的子宫内膜癌风险。所有模型均考虑了年龄，种族，体重指数（BMI），吸烟，口服避孕药，更年期激素疗法的使用和热量的摄入。我们通过距基线（≤3或> 3年）的时间和通过BMI（<25或≥25kg / m ²）的分层模型来估计关联。在16年的随访期间，我们在114414名参与者中鉴定出2329例子宫内膜癌病例。

结果

调整混杂因素后，我们观察到，随着饮食中总叶酸，天然叶酸，B2，B6和B12的摄入量的增加，子宫内膜癌的风险增加[最高五分位（Q5）与最低五分位（Q5）的风险比（HR）从1.14至1.24 Q1）]。当将随访限制在距基线3年以上时，总叶酸，天然叶酸，B6和B12摄入量较高仍与风险增加有关。我们观察到摄入最高摄入量B2的风险[Q5 vs Q1：HR 1.27 95％置信区间（CI）1.07-1.50]，B12（Q5 vs Q1：HR 1.38 CI 1.17-1.63）和蛋氨酸（Q5 vs Q1：HR 1.26） CI 1.07–1.48）在超重/肥胖的女性中，而在正常/体重不足的女性中则没有。

结论

我们的发现表明，一碳代谢在子宫内膜癌变中起作用，因此有必要在组织和细胞生物学研究中探索这一作用。