title: Effect of folic acid supplementation on cancer risk among adults with hypertension in China: A randomized clinical trial.
abstract: The relationship of folic acid supplementation with the risk of cancer remains inconclusive. We aimed to evaluate the effects of folic acid supplementation on cancer incidence among adults with hypertension without history of stroke or myocardial infarction (MI) in the China Stroke Primary Prevention Trial (CSPPT). A total of 20,702 hypertensive adults without history of stroke or MI, stratified by MTHFR C677T genotypes(CC, CT and TT), were randomly assigned to receive double-blind daily treatment with a single pill containing 10 mg enalapril and 0.8 mg folic acid(n = 10,348) or a pill containing 10 mg enalapril alone(n = 10,354). During a median treatment duration of 4.5 years, cancer occurred in 116 participants(1.12%) in the enalapril-folic acid group versus 116 participants(1.12%) in the enalapril group (HR, 1.00; 95%CI, 0.77-1.29). There was also no significant difference in the HRs for specific types of cancer(esophageal, gastric, breast, lung, colorectal, head and neck, liver and gynecologic cancer or lymphoma) or cancer mortality(HR, 1.05; 95%CI, 0.69-1.58). For participants not receiving folic acid treatment (enalapril only group), MTHFR 677 TT genotype was an independent predictor of total cancer risk compared to CC genotype (HR, 1.86; 95%CI, 1.07-3.22). Consistently, a beneficial effect was observed in participants with MTHFR TT genotype and low folate levels (<9.0 ng/mL; HR, 0.47; 95%CI, 0.24-0.94). There is no evidence that 0.8 mg daily folic acid supplementation can increase the risk of cancer incidence among adults with hypertension without history of stroke or MI in China. Our data suggest a protective effect in participants with MTHFR TT genotype and low folate levels.
authors.affiliation: National Clinical Research Center for Kidney Disease; State Key Laboratory for Organ Failure Research; Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Xianhui
authors.initials: X
authors.lastname: Qin
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing Cancer Hospital, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Shen
authors.affiliation: Medical Imaging and Minimally Invasive Interventional center, Cancer Center of Sun Yat-sen University &State Key Laboratory of Oncology in Southern China, Guangzhou, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: National Clinical Research Center for Kidney Disease; State Key Laboratory for Organ Failure Research; Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Youbao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Wang
authors.affiliation: National Clinical Research Center for Kidney Disease; State Key Laboratory for Organ Failure Research; Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Binyan
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Oncology, First People's Hospital, Lianyungang, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Oncology, Second People's Hospital, Lianyungang, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Oncology, First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lei
authors.affiliation: National Clinical Research Center for Kidney Disease; State Key Laboratory for Organ Failure Research; Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Fan Fan
authors.initials: FF
authors.lastname: Hou
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Colorectal Surgery, Peking University Cancer Hospital and Institute, Peking-Tsinghua Center for Life Sciences, Beijing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Cardiology, Peking University First Hospital, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huo
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002681:China / Q000453:epidemiology; D019587:Dietary Supplements; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004656:Enalapril / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D004656:Enalapril; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: MTHFR C677T genotypes; baseline folate levels; cancer incidence; folic acid supplementation