title: Polymorphisms of 5,10-methylenetetrahydrofolate reductase and thymidylate synthase, dietary folate intake, and the risk of leukemia in adults.
abstract: The 5,10-methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) are critical enzymes in folate metabolism. Previous studies have reported conflicting results on the associations between MTHFR/TS polymorphisms and adult leukemia risk, which may due to the lack of information on folate intake. We investigated the risks of adult leukemia with genetic polymorphisms of folate metabolic enzymes (MTHFR C677T, A1298C, and TS) and evaluated if the associations varied by dietary folate intake from a multicenter case-control study conducted in Chinese. This study comprised 442 incident adult leukemia cases and 442 outpatient controls, individually matched to cases by gender, birth quinquennium, and study site. Genotypes were determined by a polymerase chain reaction (PCR) or PCR-based restriction fragment length polymorphism assay. Dietary folate intake was assessed by face-to-face interviews using a validated food-frequency questionnaire. The MTHFR 677TT genotype conferred a significant higher risk of leukemia in males than in females and exhibited an increased risk of acute myeloid leukemia (AML) but a decreased risk of acute lymphoblastic leukemia (ALL). The MTHFR 1298AC genotype appeared to decrease the risks of leukemia in both genders, in AML and ALL. Stratified analysis by dietary folate intake showed the increased risks of leukemia with the MTHFR 677TT and TS 2R3R/2R2R genotypes were only significant in individuals with low folate intake. A significant interaction between TS polymorphism and dietary folate intake was observed (P = 0.03). This study suggests that dietary folate intake and gender may modify the associations between MTHFR/TS polymorphisms and adult leukemia risk.
authors.affiliation: School of Population Health, The University of Western Australia, M431, 35 Stirling Highway, Crawley, Perth, WA, 6009, Australia. ping.liu@research.uwa.edu.au.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: School of Population Health, The University of Western Australia, M431, 35 Stirling Highway, Crawley, Perth, WA, 6009, Australia.|Center for Healthcare Resilience and Implementation Science, Australian Institute of Health Innovation, Macquarie University, Level 6, 75 Talavera Road, Macquarie, NSW, 2109, Australia.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Women's Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou, Zhejiang, 310006, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, 79 Qingchun Road, Hangzhou, Zhejiang, 310003, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.affiliation: School of Population Health, The University of Western Australia, M431, 35 Stirling Highway, Crawley, Perth, WA, 6009, Australia.
authors.forename: C D'Arcy J
authors.initials: CD
authors.lastname: Holman
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004032:Diet; D005260:Female; D005492:Folic Acid / Q000378:metabolism* / Q000493:pharmacokinetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D012737:Sex Factors; D011795:Surveys and Questionnaires; D013940:Thymidylate Synthase / Q000235:genetics*; D055815:Young Adult
chemical_list: D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013940:Thymidylate Synthase
keywords: Adult leukemia risk; Case-control study; Dietary folate intake; Gene-environment interaction; MTHFR; TS