Li Yunshan, Shu Jing, Tan Peishan, Dong Xiaocong, Zhang Mingjie, He Tongtong, Yang Zhijun, Zhang Xuehong, Giovannucci Edward L, Liu Zhaoyan, Zhou Zhongguo, Li Qijiong, Xu Yanjun, Xu Xiaojun, Peng Tianyou, Lu Jialin, Zhang Yaojun, Zhu Huilian, Fang Aiping
Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China.
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Br J Nutr. 2024 Dec 14;132(11):1411-1422. doi: 10.1017/S0007114524001776. Epub 2024 Nov 7.
Folate metabolism is involved in the development and progression of various cancers. We investigated the association of single nucleotide polymorphisms (SNP) in folate-metabolising genes and their interactions with serum folate concentrations with overall survival (OS) and liver cancer-specific survival (LCSS) of newly diagnosed hepatocellular carcinoma (HCC) patients. We detected the genotypes of six SNP in three genes related to folate metabolism: methylenetetrahydrofolate reductase (), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase () and 5-methyltetrahydrofolate-homocysteine methyltransferase (). Cox proportional hazard models were used to calculate multivariable-adjusted hazard ratios (HR) and 95 % CI. This analysis included 970 HCC patients with genotypes of six SNP, and 864 of them had serum folate measurements. During a median follow-up of 722 d, 393 deaths occurred, with 360 attributed to HCC. In the fully-adjusted models, the rs1801394 polymorphism was significantly associated with OS in additive (per allele: HR = 0·84, 95 % CI: 0·71, 0·99), co-dominant (AG . AA: HR = 0·77; 95 % CI: 0·62, 0·96) and dominant (AG + GG . AA: HR = 0·78; 95 % CI: 0·63, 0·96) models. Carrying increasing numbers of protective alleles was linked to better LCSS (HR. = 0·70; 95 % CI: 0·49, 1·00) and OS (HR. = 0·67; 95 % CI: 0·47, 0·95). Furthermore, we observed significant interactions on both multiplicative and additive scales between serum folate levels and rs1801394 polymorphism. Carrying the variant G allele of the rs1801394 is associated with better HCC prognosis and may enhance the favourable association between higher serum folate levels and improved survival among HCC patients.
叶酸代谢参与多种癌症的发生和发展。我们研究了叶酸代谢相关基因中的单核苷酸多态性（SNP）及其与血清叶酸浓度的相互作用与新诊断肝细胞癌（HCC）患者总生存期（OS）和肝癌特异性生存期（LCSS）的关系。我们检测了与叶酸代谢相关的三个基因中六个SNP的基因型：亚甲基四氢叶酸还原酶（）、5-甲基四氢叶酸-同型半胱氨酸甲基转移酶还原酶（）和5-甲基四氢叶酸-同型半胱氨酸甲基转移酶（）。采用Cox比例风险模型计算多变量调整风险比（HR）和95%置信区间（CI）。该分析纳入了970例具有六个SNP基因型的HCC患者，其中864例有血清叶酸测量值。在中位随访722天期间，发生393例死亡，其中360例归因于HCC。在完全调整模型中，rs1801394多态性在相加模型（每增加一个等位基因：HR = 0·84，95%CI：0·71，0·99）、共显性模型（AG对AA：HR = 0·77；95%CI：0·62，0·96）和显性模型（AG + GG对AA：HR = 0·78；95%CI：0·63，0·96）中与OS显著相关。携带保护性等位基因数量增加与更好的LCSS（HR = 0·70；95%CI：0·49，1·00）和OS（HR = 0·67；95%CI：0·47，0·95）相关。此外，我们观察到血清叶酸水平与rs1801394多态性在相乘和相加尺度上均存在显著相互作用。携带rs1801394的变异G等位基因与更好的HCC预后相关，并且可能增强较高血清叶酸水平与HCC患者生存率提高之间的有利关联。
