American Journal of Epidemiology Advance Access originally published online on December 27, 2007
American Journal of Epidemiology 2008 167(5):505-516; doi:10.1093/aje/kwm344
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Meta- and Pooled Analyses of the Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms and Gastric Cancer Risk: A Huge-GSEC Review
1 Institute of Hygiene, Università Cattolica del Sacro Cuore, Rome, Italy
2 Genetic Epidemiology Cluster, International Agency for Research on Cancer, Lyon, France
3 Department of Medicine II, Klinikum rechts der Isar, Technical University of München, München, Germany
4 Shanghai Institute of Digestive Disease, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
5 Department of Epidemiology, Jiangsu Province Institute of Cancer Research, Nanjing, China
6 Division of Medical Oncology, Azienda Ospedale "San Salvatore," Pesaro, Italy
7 Andalusian School of Public Health, Granada, Spain
8 Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
9 Mexico National Institute of Public Health, Cuernavaca, Mexico
10 Department of Epidemiology, Cancer Institute, Chinese Academy of Medical Sciences, Beijing, China
11 Department of Epidemiology and Statistics, Nanjing Medical University School of Public Health, Nanjing, China
12 Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
13 Department of Epidemiology, UNT Health Science Center, Fort Worth, TX
14 Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands
15 School of Public Health, University of Pittsburgh/University of Pittsburgh Cancer Institute, Pittsburgh, PA
Correspondence to Dr. Stefania Boccia, Genetic Epidemiology and Molecular Biology Unit, Institute of Hygiene, Università Cattolica del Sacro Cuore, L.go F.Vito 1, 00168 Rome, Italy (e-mail: sboccia{at}rm.unicatt.it).
Received for publication July 25, 2007. Accepted for publication October 29, 2007.
Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, whose role in gastric carcinogenesis is controversial. The authors performed a meta-analysis and individual data pooled analysis of case-control studies that examined the association between C677T and A1298C polymorphisms (the former being associated with low folate serum levels) and gastric cancer (meta-analyses: 16 studies, 2,727 cases and 4,640 controls for C677T and seven studies, 1,223 cases and 2,015 controls for A1298C; pooled analyses: nine studies, 1,540 cases and 2,577 controls for C677T and five studies, 1,146 cases and 1,549 controls for A1298C). An increased risk was found for MTHFR 677 TT in the meta-analysis (odds ratio (OR) = 1.52, 95% confidence interval (CI): 1.31, 1.77) and pooled analysis (OR = 1.49, 95% CI: 1.14, 1.95). No association resulted for MTHFR 1298 CC (meta-OR = 0.94, 95% CI: 0.65, 1.35; pooled OR = 0.90, 95% CI: 0.69, 1.34). Results from the pooled analysis of four studies on C677T stratified according to folate levels showed an increased risk for individuals with low (OR = 2.05, 95% CI: 1.13, 3.72) versus high (OR = 0.95, 95% CI: 0.54, 1.67) folate levels. Overall, these findings support the hypothesis that folate plays a role in gastric carcinogenesis.
epidemiology; folic acid; genetic predisposition to disease; meta-analysis; MTHFR; stomach neoplasms
Abbreviations: CI, confidence interval; GSEC, Genetic Susceptibility to Environmental Carcinogens; HWE, Hardy-Weinberg equilibrium; MTHFR, methylenetetrahydrofolate reductase
Editor's note: This paper is also available on the website of the Human Genome Epidemiology Network (http://www.cdc.gov/genomics/hugenet/).
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