title: Single nucleotide polymorphisms of one-carbon metabolism and cancers of the esophagus, stomach, and liver in a Chinese population.
abstract: One-carbon metabolism (folate metabolism) is considered important in carcinogenesis because of its involvement in DNA synthesis and biological methylation reactions. We investigated the associations of single nucleotide polymorphisms (SNPs) in folate metabolic pathway and the risk of three GI cancers in a population-based case-control study in Taixing City, China, with 218 esophageal cancer cases, 206 stomach cancer cases, 204 liver cancer cases, and 415 healthy population controls. Study participants were interviewed with a standardized questionnaire, and blood samples were collected after the interviews. We genotyped SNPs of the MTHFR, MTR, MTRR, DNMT1, and ALDH2 genes, using PCR-RFLP, SNPlex, or TaqMan assays. To account for multiple comparisons and reduce the chances of false reports, we employed semi-Bayes (SB) shrinkage analysis. After shrinkage and adjusting for potential confounding factors, we found positive associations between MTHFR rs1801133 and stomach cancer (any T versus C/C, SB odds-ratio [SBOR]: 1.79, 95% posterior limits: 1.18, 2.71) and liver cancer (SBOR: 1.51, 95% posterior limits: 0.98, 2.32). There was an inverse association between DNMT1 rs2228612 and esophageal cancer (any G versus A/A, SBOR: 0.60, 95% posterior limits: 0.39, 0.94). In addition, we detected potential heterogeneity across alcohol drinking status for ORs relating MTRR rs1801394 to esophageal (posterior homogeneity P = 0.005) and stomach cancer (posterior homogeneity P = 0.004), and ORs relating MTR rs1805087 to liver cancer (posterior homogeneity P = 0.021). Among non-alcohol drinkers, the variant allele (allele G) of these two SNPs was inversely associated with the risk of these cancers; while a positive association was observed among ever-alcohol drinkers. Our results suggest that genetic polymorphisms related to one-carbon metabolism may be associated with cancers of the esophagus, stomach, and liver. Heterogeneity across alcohol consumption status of the associations between MTR/MTRR polymorphisms and these cancers indicates potential interactions between alcohol drinking and one-carbon metabolic pathway.
authors.affiliation: Department of Epidemiology, University of California Los Angeles Fielding School of Public Health, Los Angeles, CA, United States of America.
authors.forename: Shen-Chih
authors.initials: SC
authors.lastname: Chang
authors.affiliation: Department of Epidemiology, University of California Los Angeles Fielding School of Public Health, Los Angeles, CA, United States of America.
authors.forename: Po-Yin
authors.initials: PY
authors.lastname: Chang
authors.affiliation: Department of Epidemiology, University of California Los Angeles Fielding School of Public Health, Los Angeles, CA, United States of America.
authors.forename: Brendan
authors.initials: B
authors.lastname: Butler
authors.affiliation: Department of Epidemiology, University of California Los Angeles Fielding School of Public Health, Los Angeles, CA, United States of America.
authors.forename: Binh Y
authors.initials: BY
authors.lastname: Goldstein
authors.affiliation: Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY, United States of America.
authors.forename: Lina
authors.initials: L
authors.lastname: Mu
authors.affiliation: Department of Epidemiology, Fujian Medical University, Fuzhou, Fujian, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Epidemiology, University of California Los Angeles Fielding School of Public Health, Los Angeles, CA, United States of America.
authors.forename: Nai-Chieh Y
authors.initials: NC
authors.lastname: You
authors.affiliation: Department of Epidemiology, University of California Los Angeles Fielding School of Public Health, Los Angeles, CA, United States of America.
authors.forename: Aileen
authors.initials: A
authors.lastname: Baecker
authors.affiliation: Department of Epidemiology, Fudan University School of Public Health, Shanghai, China.
authors.forename: Shun-Zhang
authors.initials: SZ
authors.lastname: Yu
authors.affiliation: Center for Human Nutrition, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Heber
authors.affiliation: Center for Human Nutrition, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA, United States of America.
authors.forename: Qing-Yi
authors.initials: QY
authors.lastname: Lu
authors.affiliation: Department of Epidemiology, Peking University School of Public Health, Beijing, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Epidemiology, University of California Los Angeles Fielding School of Public Health, Los Angeles, CA, United States of America; Department of Statistics, University of California Los Angeles College of Letters and Science, Los Angeles, CA, United States of America.
authors.forename: Sander
authors.initials: S
authors.lastname: Greenland
authors.affiliation: Department of Epidemiology, University of California Los Angeles Fielding School of Public Health, Los Angeles, CA, United States of America.
authors.forename: Zuo-Feng
authors.initials: ZF
authors.lastname: Zhang
mesh_terms: D000368:Aged; D044466:Asian People; D016022:Case-Control Studies; D002681:China; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D009363:Neoplasm Proteins; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase