Esophageal and gastric cardia cancer risk and folate- and vitamin B(12)-related polymorphisms in Linxian, China.
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 B(12) 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 B(12) 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.
Stolzenberg-Solomon
Rachael Z
RZ
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20852, USA. rs221z@nih.gov
Qiao
You-Lin
YL
Abnet
Christian C
CC
Ratnasinghe
D Luke
DL
Dawsey
Sanford M
SM
Dong
Zhi Wei
ZW
Taylor
Philip R
PR
Mark
Steven D
SD
D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics*; D001426:Bacterial Proteins; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics*; D002299:Cardia / Q000473:pathology*; D002681:China; D015331:Cohort Studies; D004938:Esophageal Neoplasms / Q000209:etiology / Q000235:genetics*; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005494:Folic Acid Deficiency / Q000150:complications* / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012097:Repressor Proteins; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics*; D014806:Vitamin B 12 Deficiency / Q000150:complications* / Q000235:genetics
D001426:Bacterial Proteins; D012097:Repressor Proteins; C087450:mtrR protein, Neisseria gonorrhoeae; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2)