Single Nucleotide Polymorphisms of One-Carbon Metabolism and Cancers of the Esophagus, Stomach, and Liver in a Chinese Population
Identifieur interne : 000127 ( Main/Exploration ); précédent : 000126; suivant : 000128Single Nucleotide Polymorphisms of One-Carbon Metabolism and Cancers of the Esophagus, Stomach, and Liver in a Chinese Population
Auteurs : Shen-Chih Chang [États-Unis] ; Po-Yin Chang [États-Unis] ; Brendan Butler [États-Unis] ; Binh Y. Goldstein [États-Unis] ; Lina Mu [États-Unis] ; Lin Cai [République populaire de Chine] ; Nai-Chieh Y. You [États-Unis] ; Aileen Baecker [États-Unis] ; Shun-Zhang Yu [République populaire de Chine] ; David Heber [États-Unis] ; Qing-Yi Lu [États-Unis] ; Liming Li [République populaire de Chine] ; Sander Greenland [États-Unis] ; Zuo-Feng Zhang [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2014.
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
Url:
DOI: 10.1371/journal.pone.0109235
PubMed: 25337902
PubMed Central: 4206280
Affiliations:
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<front><div type="abstract" xml:lang="en"><p>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 <italic>MTHFR</italic>
, <italic>MTR</italic>
, <italic>MTRR</italic>
, <italic>DNMT1</italic>
, and <italic>ALDH2</italic>
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 <italic>MTHFR</italic>
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 <italic>DNMT1</italic>
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 <italic>MTRR</italic>
rs1801394 to esophageal (posterior homogeneity <italic>P</italic>
= 0.005) and stomach cancer (posterior homogeneity <italic>P</italic>
= 0.004), and ORs relating <italic>MTR</italic>
rs1805087 to liver cancer (posterior homogeneity <italic>P</italic>
= 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 <italic>MTR</italic>
/<italic>MTRR</italic>
polymorphisms and these cancers indicates potential interactions between alcohol drinking and one-carbon metabolic pathway.</p>
</div>
</front>
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<name sortKey="Chang, Po Yin" sort="Chang, Po Yin" uniqKey="Chang P" first="Po-Yin" last="Chang">Po-Yin Chang</name>
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