Esophageal and Gastric Cardia Cancer Risk and Folate- and Vitamin B12-related Polymorphisms in Linxian, China
- Rachael Z. Stolzenberg-Solomon12,
- You-Lin Qiao3,
- Christian C. Abnet4,
- D. Luke Ratnasinghe45,
- Sanford M. Dawsey4,
- Zhi Wei Dong3,
- Philip R. Taylor4 and
- Steven D. Mark6
- 1Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland;
- 2Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland;
- 3Cancer Institute, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China;
- 4Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute, Rockville, Maryland;
- 5Center for Population Genomics, National Center for Toxicology Research, Food and Drug Administration, Jefferson, Arkansas; and
- 6Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
Abstract
Linxian, a rural county in North Central China, has among the highest rates of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in the world. Its inhabitants have documented chronic nutritional inadequacies, including folate and vitamin B12 deficiencies. Using a cohort we have been studying in Linxian since 1985, we examined the relationship between incident ESCC and GCA cancers and three polymorphisms in two genes that code for enzymes that require folate and B12 as cofactors: methionine synthase reductase (MTRR) A66G and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C. We conducted a case-cohort study among 4005 individuals in our cohort who were alive and cancer free in 1991 and had blood samples adequate for DNA extraction. Polymorphisms were measured on all 219 incident cancers (129 ESCCs and 90 GCAs) that developed through May 1996 and on 398 controls. Cox proportional hazard models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Individuals with the MTHFR 677TT genotype had significantly higher combined ESCC/GCA risks (RR, 1.45; 95% CI, 1.02–2.05) than those with CC or CT genotypes. The only subjects to have MTHFR 1298CC were three ESCC cases (P = 0.03). Compared with subjects with the MTRR 66AA genotype, subjects with the AG or GG genotypes had significantly higher risk of ESCC (RR, 1.59; 95% CI, 1.04–2.42). No association was observed for GCA. Our results suggest that the MTHFR C677T and MTRR A66G polymorphisms influence the risk of ESCC and GCA in this population.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Requests for reprints: Rachael Z. Stolzenberg-Solomon, Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Suite 320 MSC 7232, Rockville, Maryland 20852. Phone: (301) 594-2939; Fax: (301) 496-6829; E-mail: rs22lz{at}nih.gov
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↵7 The abbreviations used are: ESCC, esophageal squamous cell carcinoma; GCA, gastric cardia adenocarcinoma; MTRR, methionine synthase reductase; MTHFR, methylenetetrahydrofolate reductase; RR, relative risk; CI, confidence interval; BMI, body mass index.
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- Accepted August 22, 1903.
- Received March 7, 1903.
- Revision received June 27, 1903.
