Single Nucleotide Polymorphisms of One-Carbon Metabolism and Cancers of the Esophagus, Stomach, and Liver in a Chinese Population
Identifieur interne : 000459 ( Pmc/Curation ); précédent : 000458; suivant : 000460Single 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
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DOI: 10.1371/journal.pone.0109235
PubMed: 25337902
PubMed Central: 4206280
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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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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id>
<journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosone</journal-id>
<journal-title-group><journal-title>PLoS ONE</journal-title>
</journal-title-group>
<issn pub-type="epub">1932-6203</issn>
<publisher><publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">25337902</article-id>
<article-id pub-id-type="pmc">4206280</article-id>
<article-id pub-id-type="publisher-id">PONE-D-14-05560</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0109235</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline-v2"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Genetics</subject>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v2"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Epidemiology</subject>
</subj-group>
<subj-group><subject>Gastroenterology and Hepatology</subject>
</subj-group>
<subj-group><subject>Oncology</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Single Nucleotide Polymorphisms of One-Carbon Metabolism and Cancers of the Esophagus, Stomach, and Liver in a Chinese Population</article-title>
<alt-title alt-title-type="running-head">SNPs in One-Carbon Metabolism and Upper GI Cancers</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Chang</surname>
<given-names>Shen-Chih</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chang</surname>
<given-names>Po-Yin</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Butler</surname>
<given-names>Brendan</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Goldstein</surname>
<given-names>Binh Y.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mu</surname>
<given-names>Lina</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cai</surname>
<given-names>Lin</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>You</surname>
<given-names>Nai-Chieh Y.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Baecker</surname>
<given-names>Aileen</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Yu</surname>
<given-names>Shun-Zhang</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Heber</surname>
<given-names>David</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lu</surname>
<given-names>Qing-Yi</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Li</surname>
<given-names>Liming</given-names>
</name>
<xref ref-type="aff" rid="aff6"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Greenland</surname>
<given-names>Sander</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff7"><sup>7</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Zuo-Feng</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>*</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label>
<addr-line>Department of Epidemiology, University of California Los Angeles Fielding School of Public Health, Los Angeles, CA, United States of America</addr-line>
</aff>
<aff id="aff2"><label>2</label>
<addr-line>Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY, United States of America</addr-line>
</aff>
<aff id="aff3"><label>3</label>
<addr-line>Department of Epidemiology, Fujian Medical University, Fuzhou, Fujian, China</addr-line>
</aff>
<aff id="aff4"><label>4</label>
<addr-line>Department of Epidemiology, Fudan University School of Public Health, Shanghai, China</addr-line>
</aff>
<aff id="aff5"><label>5</label>
<addr-line>Center for Human Nutrition, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA, United States of America</addr-line>
</aff>
<aff id="aff6"><label>6</label>
<addr-line>Department of Epidemiology, Peking University School of Public Health, Beijing, China</addr-line>
</aff>
<aff id="aff7"><label>7</label>
<addr-line>Department of Statistics, University of California Los Angeles College of Letters and Science, Los Angeles, CA, United States of America</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Ellis</surname>
<given-names>Nathan A.</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1"><addr-line>University of Arizona, United States of America</addr-line>
</aff>
<author-notes><corresp id="cor1">* E-mail: <email>zfzhang@ucla.edu</email>
</corresp>
<fn fn-type="conflict"><p><bold>Competing Interests: </bold>
The authors have declared that no competing interests exist.</p>
</fn>
<fn fn-type="con"><p>Conceived and designed the experiments: SCC LM LC SZY QYL ZFZ. Performed the experiments: SCC BYG LM NCYY AB. Analyzed the data: SCC PYC SG ZFZ. Contributed reagents/materials/analysis tools: DH. Wrote the paper: SCC. Interpreted the results: SCC PYC LL SG ZFZ. Participated in manuscript writing process: BB LM SZY QYL LL SG ZFZ.</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><year>2014</year>
</pub-date>
<pub-date pub-type="epub"><day>22</day>
<month>10</month>
<year>2014</year>
</pub-date>
<volume>9</volume>
<issue>10</issue>
<elocation-id>e109235</elocation-id>
<history><date date-type="received"><day>5</day>
<month>2</month>
<year>2014</year>
</date>
<date date-type="accepted"><day>9</day>
<month>9</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-year>2014</copyright-year>
<copyright-holder>Chang et al</copyright-holder>
<license><license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<abstract><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>
</abstract>
<funding-group><funding-statement>This work is supported in part by the International Union Against Cancer (UICC) Technology Transfer fellowship (ICRETT) awarded to Dr. Li-Na Mu and by the Foundation for the Author of National Excellent Doctoral Dissertation of P.R. China, No. 200157, awarded to Dr. Lin Cai. The study was also partially supported by the NIH National Institute of Environmental Health Sciences, National Cancer Institute, Department of Health and Human Services, grants ES06718, ES 011667, CA09142, as well as the Alper Research Program of Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center and the UCLA Clinical Nutrition Research Unit. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement>
</funding-group>
<counts><page-count count="16"></page-count>
</counts>
</article-meta>
</front>
</pmc>
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