Genetic variants in folate metabolism-related genes, serum folate and hepatocellular carcinoma survival: the Guangdong Liver Cancer Cohort study.

Autor: Li Y; 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., Shu J; 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., Tan P; 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., Dong X; 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., Zhang M; 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., He T; 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., Yang Z; 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., Zhang X; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Yale University School of Nursing, Orange, CT, USA., Giovannucci EL; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Liu Z; 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., Zhou Z; Department of Hepatobiliary Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China., Li Q; Department of Hepatobiliary Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China., Xu Y; Department of Chronic Noncommunicable Disease Prevention and Control, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, People's Republic of China., Xu X; Department of Chronic Noncommunicable Disease Prevention and Control, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, People's Republic of China., Peng T; 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., Lu J; 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., Zhang Y; Department of Hepatobiliary Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China., Zhu H; 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., Fang A; 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.
Jazyk: angličtina
Zdroj: The British journal of nutrition [Br J Nutr] 2024 Dec 14; Vol. 132 (11), pp. 1411-1422. Date of Electronic Publication: 2024 Nov 07.
DOI: 10.1017/S0007114524001776
Abstrakt: 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 ( MTHFR ), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase ( MTRR ) and 5-methyltetrahydrofolate-homocysteine methyltransferase ( MTR ). 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 MTRR rs1801394 polymorphism was significantly associated with OS in additive (per G allele: HR = 0·84, 95 % CI: 0·71, 0·99), co-dominant (AG v . AA: HR = 0·77; 95 % CI: 0·62, 0·96) and dominant (AG + GG v . AA: HR = 0·78; 95 % CI: 0·63, 0·96) models. Carrying increasing numbers of protective alleles was linked to better LCSS (HR 10–12 v . 2–6 = 0·70; 95 % CI: 0·49, 1·00) and OS (HR 10–12 v . 2–6 = 0·67; 95 % CI: 0·47, 0·95). Furthermore, we observed significant interactions on both multiplicative and additive scales between serum folate levels and MTRR rs1801394 polymorphism. Carrying the variant G allele of the MTRR rs1801394 is associated with better HCC prognosis and may enhance the favourable association between higher serum folate levels and improved survival among HCC patients.
Databáze: MEDLINE