MTHFR 基因中的 C677T 多态性及其在叶酸代谢中的作用，影响 THF 和 5-MTHF 等血清叶酸代谢物，是癌症研究中一个关键但尚未充分探索的领域。这项巢式病例对照研究利用了 CHHRS 的数据，涉及 87,492 名既往无癌症史的高血压成人。在平均 2.02 年的时间里，我们识别出了 1332 例癌症病例，并根据年龄、性别和居住地进行了匹配对照。测定血清叶酸、THF、5-MTHF水平，并考虑MTHFR C677T基因多态性。统计分析包括限制三次样条回归和条件逻辑回归模型。血清 THF 水平与总体癌症风险呈负相关（ORper SD = 0.90，95% CI = 0.82-0.99），而 5-MTHF 水平在一般队列中显示出负相关（ORQ3 vs. Q1 = 0.76，95% CI = 0.60-0.96；ORQ4 vs. Q1 = 0.75，95% CI = 0.58-0.98）以及具有 MTHFR C677T (CC  CT) 多态性的个体（ORper SD = 0.87，95% CI = 0.77-0.99；ORQ4 VS. Q1 = 0.79 ，95％CI = 0.61-0.98），但是MTHFR C677T（TT）子组呈正相关（ORPER SD = 1.89，95％CI = 1.02-3.72; orq4 vs. Q1 vs. Q1 = 2.17，95％CI = 1.06-8.2111 ）。叶酸、THF 和 5-MTHF 对癌症风险的影响在不同癌症类型和 MTHFR C677T 基因型之间存在显着差异。这项研究为叶酸及其代谢物对癌症风险的不同影响提供了新的见解，这些影响受 MTHFR C677T 多态性和癌症类型等遗传因素的影响。© 2024 作者。约翰·威利出版的《国际癌症杂志》

The C677T polymorphism in the MTHFR gene and its role in folate metabolism, impacting serum folate metabolites like THF and 5-MTHF, is a critical but underexplored area in cancer research. This nested case-control study utilized data from CHHRS, involving 87,492 hypertensive adults without prior cancer. During a median of 2.02 years, we identified 1332 cancer cases and matched controls based on age, sex, and residency. Serum levels of folate, THF, and 5-MTHF were measured, and the MTHFR C677T gene polymorphism was considered. Statistical analyses included restricted cubic spline regression and conditional logistic regression models. Serum THF levels were inversely associated with overall cancer risk (ORper SD = 0.90, 95% CI = 0.82-0.99), while 5-MTHF levels showed a negative association in the general cohort (ORQ3 vs. Q1 = 0.76, 95% CI = 0.60-0.96; ORQ4 vs. Q1 = 0.75, 95% CI = 0.58-0.98) and in individuals with MTHFR C677T (CC + CT) polymorphism (ORper SD = 0.87, 95% CI = 0.77-0.99; ORQ4 VS. Q1 = 0.79, 95% CI = 0.61-0.98), but a positive association in the MTHFR C677T (TT) subgroup (ORper SD = 1.89, 95% CI = 1.02-3.72; ORQ4 VS. Q1 = 2.17, 95% CI = 1.06-8.21). The impact of folate, THF, and 5-MTHF on cancer risk varied significantly across different cancer types and MTHFR C677T genotypes. This study provides novel insights into the variable effects of folate and its metabolites on cancer risk, influenced by genetic factors like the MTHFR C677T polymorphism and cancer type.© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.