Genetic polymorphisms at TIMP3 are associated with survival of adenocarcinoma of the gastroesophageal junction
The poor survival of adenocarcinomas of the gastroesophageal junction (GEJ) makes them clinically important. Discovery of host genetic factors that affect outcome may guide more individualized treatment. This study tests whether constitutional genetic variants in matrix metalloproteinases (MMP) and...
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| Veröffentlicht in: | PloS one 2013-03, Vol.8 (3), p.e59157-e59157 |
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| creator | Bashash, Morteza Shah, Amil Hislop, Greg Treml, Martin Bretherick, Karla Janoo-Gilani, Rozmin Leach, Stephen Le, Nhu Bajdik, Chris Brooks-Wilson, Angela |
| description | The poor survival of adenocarcinomas of the gastroesophageal junction (GEJ) makes them clinically important. Discovery of host genetic factors that affect outcome may guide more individualized treatment. This study tests whether constitutional genetic variants in matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) genes are associated with outcome of GEJ adenocarcinoma. Single nucleotide polymorphisms (SNPs) at four TIMP (TIMP1-4) and three MMP genes (MMP2, MMP7 and MMP9) were genotyped in DNA samples from a prospective cohort of patients with primary adenocarcinoma of the GEJ admitted to the British Columbia Cancer Agency. Cox proportional hazards regression, with adjustment for patient, disease and treatment variables, was used to estimate the association of SNPs with survival. Genotypes for 85 samples and 48 SNPs were analyzed. Four SNPs across TIMP3, (rs130274, rs715572, rs1962223 and rs5754312) were associated with survival. Interaction analyses revealed that the survival associations with rs715572 and rs5754312 are specific and significant for 5FU+cisplatin treated patients. Sanger sequencing of the TIMP3 coding and promoter regions revealed an additional SNP, rs9862, also associated with survival. TIMP3 genetic variants are associated with survival and may be potentially useful in optimizing treatment strategies for individual patients. |
| doi_str_mv | 10.1371/journal.pone.0059157 |
| format | Article |
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Discovery of host genetic factors that affect outcome may guide more individualized treatment. This study tests whether constitutional genetic variants in matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) genes are associated with outcome of GEJ adenocarcinoma. Single nucleotide polymorphisms (SNPs) at four TIMP (TIMP1-4) and three MMP genes (MMP2, MMP7 and MMP9) were genotyped in DNA samples from a prospective cohort of patients with primary adenocarcinoma of the GEJ admitted to the British Columbia Cancer Agency. Cox proportional hazards regression, with adjustment for patient, disease and treatment variables, was used to estimate the association of SNPs with survival. Genotypes for 85 samples and 48 SNPs were analyzed. Four SNPs across TIMP3, (rs130274, rs715572, rs1962223 and rs5754312) were associated with survival. Interaction analyses revealed that the survival associations with rs715572 and rs5754312 are specific and significant for 5FU+cisplatin treated patients. Sanger sequencing of the TIMP3 coding and promoter regions revealed an additional SNP, rs9862, also associated with survival. TIMP3 genetic variants are associated with survival and may be potentially useful in optimizing treatment strategies for individual patients.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0059157</identifier><identifier>PMID: 23527119</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenocarcinoma ; Adenocarcinoma - drug therapy ; Adenocarcinoma - genetics ; Adenocarcinoma - mortality ; Adenocarcinoma - pathology ; Aged ; Aged, 80 and over ; Angiogenesis ; Base Sequence ; Biology ; Cancer therapies ; Chemotherapy ; Cisplatin ; Deoxyribonucleic acid ; DNA ; DNA methylation ; DNA sequencing ; Esophageal cancer ; Esophageal Neoplasms - drug therapy ; Esophageal Neoplasms - genetics ; Esophageal Neoplasms - mortality ; Esophageal Neoplasms - pathology ; Esophagogastric Junction - pathology ; Female ; Gelatinase A ; Gelatinase B ; Gene Order ; Genes ; Genetic aspects ; Genetic diversity ; Genetic factors ; Genetic testing ; Genetic variance ; Genomes ; Genotype ; Genotypes ; Hazards ; Humans ; Kinases ; Male ; Matrilysin ; Matrix metalloproteinases ; Medical prognosis ; Medical treatment ; Medicine ; Metastasis ; Middle Aged ; Molecular Sequence Data ; Neoplasm Staging ; Oncology ; Patients ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Population ; Public health ; Regression analysis ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Stomach Neoplasms - drug therapy ; Stomach Neoplasms - genetics ; Stomach Neoplasms - mortality ; Stomach Neoplasms - pathology ; Survival ; Tissue inhibitor of metalloproteinase 1 ; Tissue inhibitor of metalloproteinase 3 ; Tissue Inhibitor of Metalloproteinase-3 - chemistry ; Tissue Inhibitor of Metalloproteinase-3 - genetics ; Treatment Outcome</subject><ispartof>PloS one, 2013-03, Vol.8 (3), p.e59157-e59157</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Bashash et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Bashash et al 2013 Bashash et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-56fdb5d602ef3804bb51c49ea593138107c65207b3d7a9ffb017ec85e07f77293</citedby><cites>FETCH-LOGICAL-c692t-56fdb5d602ef3804bb51c49ea593138107c65207b3d7a9ffb017ec85e07f77293</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602604/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602604/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23527119$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Mittal, Balraj</contributor><creatorcontrib>Bashash, Morteza</creatorcontrib><creatorcontrib>Shah, Amil</creatorcontrib><creatorcontrib>Hislop, Greg</creatorcontrib><creatorcontrib>Treml, Martin</creatorcontrib><creatorcontrib>Bretherick, Karla</creatorcontrib><creatorcontrib>Janoo-Gilani, Rozmin</creatorcontrib><creatorcontrib>Leach, Stephen</creatorcontrib><creatorcontrib>Le, Nhu</creatorcontrib><creatorcontrib>Bajdik, Chris</creatorcontrib><creatorcontrib>Brooks-Wilson, Angela</creatorcontrib><title>Genetic polymorphisms at TIMP3 are associated with survival of adenocarcinoma of the gastroesophageal junction</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The poor survival of adenocarcinomas of the gastroesophageal junction (GEJ) makes them clinically important. Discovery of host genetic factors that affect outcome may guide more individualized treatment. This study tests whether constitutional genetic variants in matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) genes are associated with outcome of GEJ adenocarcinoma. Single nucleotide polymorphisms (SNPs) at four TIMP (TIMP1-4) and three MMP genes (MMP2, MMP7 and MMP9) were genotyped in DNA samples from a prospective cohort of patients with primary adenocarcinoma of the GEJ admitted to the British Columbia Cancer Agency. Cox proportional hazards regression, with adjustment for patient, disease and treatment variables, was used to estimate the association of SNPs with survival. Genotypes for 85 samples and 48 SNPs were analyzed. Four SNPs across TIMP3, (rs130274, rs715572, rs1962223 and rs5754312) were associated with survival. Interaction analyses revealed that the survival associations with rs715572 and rs5754312 are specific and significant for 5FU+cisplatin treated patients. Sanger sequencing of the TIMP3 coding and promoter regions revealed an additional SNP, rs9862, also associated with survival. TIMP3 genetic variants are associated with survival and may be potentially useful in optimizing treatment strategies for individual patients.</description><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - drug therapy</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - mortality</subject><subject>Adenocarcinoma - pathology</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Angiogenesis</subject><subject>Base Sequence</subject><subject>Biology</subject><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>Cisplatin</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>DNA sequencing</subject><subject>Esophageal cancer</subject><subject>Esophageal Neoplasms - drug therapy</subject><subject>Esophageal Neoplasms - genetics</subject><subject>Esophageal Neoplasms - mortality</subject><subject>Esophageal Neoplasms - pathology</subject><subject>Esophagogastric Junction - pathology</subject><subject>Female</subject><subject>Gelatinase A</subject><subject>Gelatinase B</subject><subject>Gene Order</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic factors</subject><subject>Genetic testing</subject><subject>Genetic variance</subject><subject>Genomes</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>Hazards</subject><subject>Humans</subject><subject>Kinases</subject><subject>Male</subject><subject>Matrilysin</subject><subject>Matrix metalloproteinases</subject><subject>Medical prognosis</subject><subject>Medical treatment</subject><subject>Medicine</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Neoplasm Staging</subject><subject>Oncology</subject><subject>Patients</subject><subject>Polymorphism, Genetic</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population</subject><subject>Public health</subject><subject>Regression analysis</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Stomach Neoplasms - drug therapy</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - mortality</subject><subject>Stomach Neoplasms - pathology</subject><subject>Survival</subject><subject>Tissue inhibitor of metalloproteinase 1</subject><subject>Tissue inhibitor of metalloproteinase 3</subject><subject>Tissue Inhibitor of Metalloproteinase-3 - chemistry</subject><subject>Tissue Inhibitor of Metalloproteinase-3 - genetics</subject><subject>Treatment Outcome</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk8Fu1DAQhiMEoqXwBggiISE47GLHcRxfkKqqlJWKiqBwtRzbSbxK7GA7S_v2OGxabVAPyIdEk2_-8fyZSZKXEKwhIvDD1o7O8G49WKPWAGAKMXmUHEOKslWRAfT44P0oeeb9NkKoLIqnyVGGcEYgpMeJuVBGBS3SwXa3vXVDq33vUx7S682XryjlTqXceys0D0qmv3VoUz-6nd7xLrV1yqUyVnAntLE9nyKhVWnDfXBWeTu0vFGR3I5GBG3N8-RJzTuvXszPk-THp_Prs8-ry6uLzdnp5UoUNAsrXNSywrIAmapRCfKqwlDkVHFMEUQlBEQUOAOkQpJwWtcVgESJEitAakIyik6S13vdobOezVZ5BhECZUlzACKx2RPS8i0bnO65u2WWa_Y3YF3DuIvGdIphkUNc0kzGonkNyzLPok5G4yFUShm1Ps7VxqpXUigTHO8WossvRressTuGYocFyKPAu1nA2V-j8oH12gvVddwoO073hrSABFAc0Tf_oA93N1MNjw1oU9tYV0yi7DQnZbSOkMml9QNUPFL1WsS5qnWMLxLeLxIiE9RNaPjoPdt8__b_7NXPJfv2gG3jxITW226cRsYvwXwPCme9d6q-NxkCNq3FnRtsWgs2r0VMe3X4g-6T7vYA_QFt_QeS</recordid><startdate>20130319</startdate><enddate>20130319</enddate><creator>Bashash, Morteza</creator><creator>Shah, Amil</creator><creator>Hislop, Greg</creator><creator>Treml, Martin</creator><creator>Bretherick, Karla</creator><creator>Janoo-Gilani, Rozmin</creator><creator>Leach, Stephen</creator><creator>Le, Nhu</creator><creator>Bajdik, Chris</creator><creator>Brooks-Wilson, Angela</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130319</creationdate><title>Genetic polymorphisms at TIMP3 are associated with survival of adenocarcinoma of the gastroesophageal junction</title><author>Bashash, Morteza ; Shah, Amil ; Hislop, Greg ; Treml, Martin ; Bretherick, Karla ; Janoo-Gilani, Rozmin ; Leach, Stephen ; Le, Nhu ; Bajdik, Chris ; Brooks-Wilson, Angela</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-56fdb5d602ef3804bb51c49ea593138107c65207b3d7a9ffb017ec85e07f77293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adenocarcinoma</topic><topic>Adenocarcinoma - drug therapy</topic><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - mortality</topic><topic>Adenocarcinoma - pathology</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Angiogenesis</topic><topic>Base Sequence</topic><topic>Biology</topic><topic>Cancer therapies</topic><topic>Chemotherapy</topic><topic>Cisplatin</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>DNA sequencing</topic><topic>Esophageal cancer</topic><topic>Esophageal Neoplasms - drug therapy</topic><topic>Esophageal Neoplasms - genetics</topic><topic>Esophageal Neoplasms - mortality</topic><topic>Esophageal Neoplasms - pathology</topic><topic>Esophagogastric Junction - pathology</topic><topic>Female</topic><topic>Gelatinase A</topic><topic>Gelatinase B</topic><topic>Gene Order</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic diversity</topic><topic>Genetic factors</topic><topic>Genetic testing</topic><topic>Genetic variance</topic><topic>Genomes</topic><topic>Genotype</topic><topic>Genotypes</topic><topic>Hazards</topic><topic>Humans</topic><topic>Kinases</topic><topic>Male</topic><topic>Matrilysin</topic><topic>Matrix metalloproteinases</topic><topic>Medical prognosis</topic><topic>Medical treatment</topic><topic>Medicine</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Neoplasm Staging</topic><topic>Oncology</topic><topic>Patients</topic><topic>Polymorphism, Genetic</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population</topic><topic>Public health</topic><topic>Regression analysis</topic><topic>Single nucleotide polymorphisms</topic><topic>Single-nucleotide polymorphism</topic><topic>Stomach Neoplasms - drug therapy</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stomach Neoplasms - mortality</topic><topic>Stomach Neoplasms - pathology</topic><topic>Survival</topic><topic>Tissue inhibitor of metalloproteinase 1</topic><topic>Tissue inhibitor of metalloproteinase 3</topic><topic>Tissue Inhibitor of Metalloproteinase-3 - chemistry</topic><topic>Tissue Inhibitor of Metalloproteinase-3 - genetics</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bashash, Morteza</creatorcontrib><creatorcontrib>Shah, Amil</creatorcontrib><creatorcontrib>Hislop, Greg</creatorcontrib><creatorcontrib>Treml, Martin</creatorcontrib><creatorcontrib>Bretherick, Karla</creatorcontrib><creatorcontrib>Janoo-Gilani, Rozmin</creatorcontrib><creatorcontrib>Leach, Stephen</creatorcontrib><creatorcontrib>Le, Nhu</creatorcontrib><creatorcontrib>Bajdik, Chris</creatorcontrib><creatorcontrib>Brooks-Wilson, Angela</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bashash, Morteza</au><au>Shah, Amil</au><au>Hislop, Greg</au><au>Treml, Martin</au><au>Bretherick, Karla</au><au>Janoo-Gilani, Rozmin</au><au>Leach, Stephen</au><au>Le, Nhu</au><au>Bajdik, Chris</au><au>Brooks-Wilson, Angela</au><au>Mittal, Balraj</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic polymorphisms at TIMP3 are associated with survival of adenocarcinoma of the gastroesophageal junction</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-03-19</date><risdate>2013</risdate><volume>8</volume><issue>3</issue><spage>e59157</spage><epage>e59157</epage><pages>e59157-e59157</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The poor survival of adenocarcinomas of the gastroesophageal junction (GEJ) makes them clinically important. Discovery of host genetic factors that affect outcome may guide more individualized treatment. This study tests whether constitutional genetic variants in matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) genes are associated with outcome of GEJ adenocarcinoma. Single nucleotide polymorphisms (SNPs) at four TIMP (TIMP1-4) and three MMP genes (MMP2, MMP7 and MMP9) were genotyped in DNA samples from a prospective cohort of patients with primary adenocarcinoma of the GEJ admitted to the British Columbia Cancer Agency. Cox proportional hazards regression, with adjustment for patient, disease and treatment variables, was used to estimate the association of SNPs with survival. Genotypes for 85 samples and 48 SNPs were analyzed. Four SNPs across TIMP3, (rs130274, rs715572, rs1962223 and rs5754312) were associated with survival. Interaction analyses revealed that the survival associations with rs715572 and rs5754312 are specific and significant for 5FU+cisplatin treated patients. Sanger sequencing of the TIMP3 coding and promoter regions revealed an additional SNP, rs9862, also associated with survival. TIMP3 genetic variants are associated with survival and may be potentially useful in optimizing treatment strategies for individual patients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23527119</pmid><doi>10.1371/journal.pone.0059157</doi><tpages>e59157</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1330889400 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenocarcinoma Adenocarcinoma - drug therapy Adenocarcinoma - genetics Adenocarcinoma - mortality Adenocarcinoma - pathology Aged Aged, 80 and over Angiogenesis Base Sequence Biology Cancer therapies Chemotherapy Cisplatin Deoxyribonucleic acid DNA DNA methylation DNA sequencing Esophageal cancer Esophageal Neoplasms - drug therapy Esophageal Neoplasms - genetics Esophageal Neoplasms - mortality Esophageal Neoplasms - pathology Esophagogastric Junction - pathology Female Gelatinase A Gelatinase B Gene Order Genes Genetic aspects Genetic diversity Genetic factors Genetic testing Genetic variance Genomes Genotype Genotypes Hazards Humans Kinases Male Matrilysin Matrix metalloproteinases Medical prognosis Medical treatment Medicine Metastasis Middle Aged Molecular Sequence Data Neoplasm Staging Oncology Patients Polymorphism, Genetic Polymorphism, Single Nucleotide Population Public health Regression analysis Single nucleotide polymorphisms Single-nucleotide polymorphism Stomach Neoplasms - drug therapy Stomach Neoplasms - genetics Stomach Neoplasms - mortality Stomach Neoplasms - pathology Survival Tissue inhibitor of metalloproteinase 1 Tissue inhibitor of metalloproteinase 3 Tissue Inhibitor of Metalloproteinase-3 - chemistry Tissue Inhibitor of Metalloproteinase-3 - genetics Treatment Outcome |
| title | Genetic polymorphisms at TIMP3 are associated with survival of adenocarcinoma of the gastroesophageal junction |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T15%3A06%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genetic%20polymorphisms%20at%20TIMP3%20are%20associated%20with%20survival%20of%20adenocarcinoma%20of%20the%20gastroesophageal%20junction&rft.jtitle=PloS%20one&rft.au=Bashash,%20Morteza&rft.date=2013-03-19&rft.volume=8&rft.issue=3&rft.spage=e59157&rft.epage=e59157&rft.pages=e59157-e59157&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0059157&rft_dat=%3Cgale_plos_%3EA478207779%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1330889400&rft_id=info:pmid/23527119&rft_galeid=A478207779&rft_doaj_id=oai_doaj_org_article_5c415892dc654f188423302929279ddd&rfr_iscdi=true |