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A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU oxaliplatin combination chemotherapy in refractory colorectal cancer
In this marker evaluation study, we tested whether distinct patterns of functional genomic polymorphisms in genes involved in drug metabolic pathways and DNA repair that predict clinical outcome to 5-fluorouracil (5-FU)/oxaliplatin chemotherapy in patients with advanced colorectal cancer could be id...
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| Published in: | British journal of cancer 2004-07, Vol.91 (2), p.344-354 |
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| container_title | British journal of cancer |
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| creator | Stoehlmacher, J Park, D J Zhang, W Yang, D Groshen, S Zahedy, S Lenz, H-J |
| description | In this marker evaluation study, we tested whether distinct patterns of functional genomic polymorphisms in genes involved in drug metabolic pathways and DNA repair that predict clinical outcome to 5-fluorouracil (5-FU)/oxaliplatin chemotherapy in patients with advanced colorectal cancer could be identified. Functional polymorphisms in DNA-repair genes XPD, ERCC1, XRCC1, XPA, and metabolising genes glutathione
S
-transferase GSTP1, GSTT1, GSTM1, and thymidylate synthase (TS) were assessed retrospectively in 106 patients with refractory stage IV disease who received 5-FU/oxaliplatin combination chemotherapy, using a polymerase chain reaction-based RFLP technique. Favourable genotypes from polymorphisms in XPD-751, ERCC1-118, GSTP1-105, and TS-3′-untranslated region (3′UTR) that are associated with overall survival were identified. After adjustment for performance status, the relative risks of dying for patients who possessed the unfavourable genotype were: 3.33 for XPD-751 (
P
=0.037), 3.25 for GSTP1-105 (
P
=0.072), 2.05 for ERCC1-118 (
P
=0.037), and 1.65 for TS-3′UTR (
P
=0.091) when compared to their respective beneficial genomic variants. Combination analysis with all four polymorphisms revealed that patients possessing ⩾2 favourable genotypes survived a median of 17.4 months (95% confidence interval (CI): 9.4, 26.5) compared to 5.4 months (95% CI: 4.3, 6.0) in patients with no favourable genotype. Patients who carried one favourable genotype demonstrated intermediate survival of 10.2 months (95% CI: 6.8, 15.3;
P |
| doi_str_mv | 10.1038/sj.bjc.6601975 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2409815</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>984037701</sourcerecordid><originalsourceid>FETCH-LOGICAL-c571t-fa6a3b7852eb358ea9a43a0688ea965d2912f55d6fa608fb3ed71d654f441a093</originalsourceid><addsrcrecordid>eNp1kUFv1DAQhS0EosvClRvIQuKYre3EScwBqapaQKrEhZ6tiePsOkrsYDsV-TH813rZ0JYDJ9t637wZz0PoLSU7SvL6PPS7ple7siRUVPwZ2lCes4zWrHqONoSQKiOCkTP0KoQ-PQWpq5fojHJG84rmG_T7Ao_zEM0deANRY7AwLMEE7Dq819aNRuHJDcvo_HQwYQyf8OR1a1Q0zh4hNRhrFAzYzVG5UePoMM-ub7H7BYOZBojG4iQ0xsKfGnXQo4sH7WFacNK87jyo6PySsMF5rWJyU2CV9q_Riw6GoN-s5xbdXl_9uPya3Xz_8u3y4iZTvKIx66CEvKlqznST81qDgCIHUtbHa8lbJijrOG_LBJK6a3LdVrQtedEVBQUi8i36fPKd5mbUrdI2ehjk5M0IfpEOjPxXseYg9-5OsoKIOq18iz6sBt79nHWIsnezT7sMkjEhKlHmLEG7E6S8CyH9-6EBJfKYpgy9TGnKNc1U8P7pWI_4Gl8CPq4AhJRBWqRVJjzhRFlwVifu_MSFJNm99o_j_bf1u1NFSm32-sHyr34Pl6THtQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>229979632</pqid></control><display><type>article</type><title>A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU oxaliplatin combination chemotherapy in refractory colorectal cancer</title><source>PubMed Central Free</source><creator>Stoehlmacher, J ; Park, D J ; Zhang, W ; Yang, D ; Groshen, S ; Zahedy, S ; Lenz, H-J</creator><creatorcontrib>Stoehlmacher, J ; Park, D J ; Zhang, W ; Yang, D ; Groshen, S ; Zahedy, S ; Lenz, H-J</creatorcontrib><description>In this marker evaluation study, we tested whether distinct patterns of functional genomic polymorphisms in genes involved in drug metabolic pathways and DNA repair that predict clinical outcome to 5-fluorouracil (5-FU)/oxaliplatin chemotherapy in patients with advanced colorectal cancer could be identified. Functional polymorphisms in DNA-repair genes XPD, ERCC1, XRCC1, XPA, and metabolising genes glutathione
S
-transferase GSTP1, GSTT1, GSTM1, and thymidylate synthase (TS) were assessed retrospectively in 106 patients with refractory stage IV disease who received 5-FU/oxaliplatin combination chemotherapy, using a polymerase chain reaction-based RFLP technique. Favourable genotypes from polymorphisms in XPD-751, ERCC1-118, GSTP1-105, and TS-3′-untranslated region (3′UTR) that are associated with overall survival were identified. After adjustment for performance status, the relative risks of dying for patients who possessed the unfavourable genotype were: 3.33 for XPD-751 (
P
=0.037), 3.25 for GSTP1-105 (
P
=0.072), 2.05 for ERCC1-118 (
P
=0.037), and 1.65 for TS-3′UTR (
P
=0.091) when compared to their respective beneficial genomic variants. Combination analysis with all four polymorphisms revealed that patients possessing ⩾2 favourable genotypes survived a median of 17.4 months (95% confidence interval (CI): 9.4, 26.5) compared to 5.4 months (95% CI: 4.3, 6.0) in patients with no favourable genotype. Patients who carried one favourable genotype demonstrated intermediate survival of 10.2 months (95% CI: 6.8, 15.3;
P
<0.001). Polymorphisms in the TS-3′UTR and GSTP1-105 gene were also associated with time to progression. After adjustment for performance status, patients with an unfavourable TS-3′UTR genotype had a relative risk of disease progression of 1.76 (
P
=0.020) and those with the unfavourable GSTP1-105 genotype showed a relative risk of progression of 2.00 (
P
=0.018). The genomic polymorphisms XPD-751, ERCC1-118, GSTP1-105, and TS-3′UTR may be useful in predicting overall survival and time to progression of colorectal cancer in patients who receive 5-FU/oxaliplatin chemotherapy. These findings require independent prospective confirmation.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/sj.bjc.6601975</identifier><identifier>PMID: 15213713</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Acyltransferases - genetics ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Biomarkers, Tumor - genetics ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cancer therapies ; Chemotherapy ; Clinical outcomes ; Colorectal cancer ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - pathology ; Disease Progression ; DNA Helicases ; DNA Repair ; DNA-Binding Proteins - genetics ; Drug Resistance ; Endonucleases - genetics ; Enzymes ; Epidemiology ; Female ; Fluorouracil - administration & dosage ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Expression Regulation, Neoplastic ; Genes ; Genetics and Genomics ; Genotype & phenotype ; Glutathione Transferase - genetics ; Humans ; Male ; Medical research ; Medical sciences ; Middle Aged ; Molecular Medicine ; Multivariate analysis ; Oncology ; Organoplatinum Compounds - administration & dosage ; Oxaliplatin ; Polymorphism ; Polymorphism, Genetic - genetics ; Predictive Value of Tests ; Proteins - genetics ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - metabolism ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Survival Rate ; Thymidylate Synthase - genetics ; Time Factors ; Toxicity ; Transcription Factors ; Treatment Outcome ; Tumors ; X-ray Repair Cross Complementing Protein 1 ; Xeroderma Pigmentosum Group A Protein ; Xeroderma Pigmentosum Group D Protein</subject><ispartof>British journal of cancer, 2004-07, Vol.91 (2), p.344-354</ispartof><rights>The Author(s) 2004</rights><rights>2004 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Jul 19, 2004</rights><rights>Copyright © 2004 Cancer Research UK 2004 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c571t-fa6a3b7852eb358ea9a43a0688ea965d2912f55d6fa608fb3ed71d654f441a093</citedby><cites>FETCH-LOGICAL-c571t-fa6a3b7852eb358ea9a43a0688ea965d2912f55d6fa608fb3ed71d654f441a093</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/PMC2409815/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409815/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15964528$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15213713$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stoehlmacher, J</creatorcontrib><creatorcontrib>Park, D J</creatorcontrib><creatorcontrib>Zhang, W</creatorcontrib><creatorcontrib>Yang, D</creatorcontrib><creatorcontrib>Groshen, S</creatorcontrib><creatorcontrib>Zahedy, S</creatorcontrib><creatorcontrib>Lenz, H-J</creatorcontrib><title>A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU oxaliplatin combination chemotherapy in refractory colorectal cancer</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>In this marker evaluation study, we tested whether distinct patterns of functional genomic polymorphisms in genes involved in drug metabolic pathways and DNA repair that predict clinical outcome to 5-fluorouracil (5-FU)/oxaliplatin chemotherapy in patients with advanced colorectal cancer could be identified. Functional polymorphisms in DNA-repair genes XPD, ERCC1, XRCC1, XPA, and metabolising genes glutathione
S
-transferase GSTP1, GSTT1, GSTM1, and thymidylate synthase (TS) were assessed retrospectively in 106 patients with refractory stage IV disease who received 5-FU/oxaliplatin combination chemotherapy, using a polymerase chain reaction-based RFLP technique. Favourable genotypes from polymorphisms in XPD-751, ERCC1-118, GSTP1-105, and TS-3′-untranslated region (3′UTR) that are associated with overall survival were identified. After adjustment for performance status, the relative risks of dying for patients who possessed the unfavourable genotype were: 3.33 for XPD-751 (
P
=0.037), 3.25 for GSTP1-105 (
P
=0.072), 2.05 for ERCC1-118 (
P
=0.037), and 1.65 for TS-3′UTR (
P
=0.091) when compared to their respective beneficial genomic variants. Combination analysis with all four polymorphisms revealed that patients possessing ⩾2 favourable genotypes survived a median of 17.4 months (95% confidence interval (CI): 9.4, 26.5) compared to 5.4 months (95% CI: 4.3, 6.0) in patients with no favourable genotype. Patients who carried one favourable genotype demonstrated intermediate survival of 10.2 months (95% CI: 6.8, 15.3;
P
<0.001). Polymorphisms in the TS-3′UTR and GSTP1-105 gene were also associated with time to progression. After adjustment for performance status, patients with an unfavourable TS-3′UTR genotype had a relative risk of disease progression of 1.76 (
P
=0.020) and those with the unfavourable GSTP1-105 genotype showed a relative risk of progression of 2.00 (
P
=0.018). The genomic polymorphisms XPD-751, ERCC1-118, GSTP1-105, and TS-3′UTR may be useful in predicting overall survival and time to progression of colorectal cancer in patients who receive 5-FU/oxaliplatin chemotherapy. These findings require independent prospective confirmation.</description><subject>Acyltransferases - genetics</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>Clinical outcomes</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Disease Progression</subject><subject>DNA Helicases</subject><subject>DNA Repair</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Drug Resistance</subject><subject>Endonucleases - genetics</subject><subject>Enzymes</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Fluorouracil - administration & dosage</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Genetics and Genomics</subject><subject>Genotype & phenotype</subject><subject>Glutathione Transferase - genetics</subject><subject>Humans</subject><subject>Male</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Molecular Medicine</subject><subject>Multivariate analysis</subject><subject>Oncology</subject><subject>Organoplatinum Compounds - administration & dosage</subject><subject>Oxaliplatin</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Predictive Value of Tests</subject><subject>Proteins - genetics</subject><subject>Retrospective Studies</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - metabolism</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Survival Rate</subject><subject>Thymidylate Synthase - genetics</subject><subject>Time Factors</subject><subject>Toxicity</subject><subject>Transcription Factors</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>X-ray Repair Cross Complementing Protein 1</subject><subject>Xeroderma Pigmentosum Group A Protein</subject><subject>Xeroderma Pigmentosum Group D Protein</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><recordid>eNp1kUFv1DAQhS0EosvClRvIQuKYre3EScwBqapaQKrEhZ6tiePsOkrsYDsV-TH813rZ0JYDJ9t637wZz0PoLSU7SvL6PPS7ple7siRUVPwZ2lCes4zWrHqONoSQKiOCkTP0KoQ-PQWpq5fojHJG84rmG_T7Ao_zEM0deANRY7AwLMEE7Dq819aNRuHJDcvo_HQwYQyf8OR1a1Q0zh4hNRhrFAzYzVG5UePoMM-ub7H7BYOZBojG4iQ0xsKfGnXQo4sH7WFacNK87jyo6PySsMF5rWJyU2CV9q_Riw6GoN-s5xbdXl_9uPya3Xz_8u3y4iZTvKIx66CEvKlqznST81qDgCIHUtbHa8lbJijrOG_LBJK6a3LdVrQtedEVBQUi8i36fPKd5mbUrdI2ehjk5M0IfpEOjPxXseYg9-5OsoKIOq18iz6sBt79nHWIsnezT7sMkjEhKlHmLEG7E6S8CyH9-6EBJfKYpgy9TGnKNc1U8P7pWI_4Gl8CPq4AhJRBWqRVJjzhRFlwVifu_MSFJNm99o_j_bf1u1NFSm32-sHyr34Pl6THtQ</recordid><startdate>20040719</startdate><enddate>20040719</enddate><creator>Stoehlmacher, J</creator><creator>Park, D J</creator><creator>Zhang, W</creator><creator>Yang, D</creator><creator>Groshen, S</creator><creator>Zahedy, S</creator><creator>Lenz, H-J</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>IQODW</scope><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>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>5PM</scope></search><sort><creationdate>20040719</creationdate><title>A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU oxaliplatin combination chemotherapy in refractory colorectal cancer</title><author>Stoehlmacher, J ; Park, D J ; Zhang, W ; Yang, D ; Groshen, S ; Zahedy, S ; Lenz, H-J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c571t-fa6a3b7852eb358ea9a43a0688ea965d2912f55d6fa608fb3ed71d654f441a093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Acyltransferases - genetics</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Cancer therapies</topic><topic>Chemotherapy</topic><topic>Clinical outcomes</topic><topic>Colorectal cancer</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Disease Progression</topic><topic>DNA Helicases</topic><topic>DNA Repair</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Drug Resistance</topic><topic>Endonucleases - genetics</topic><topic>Enzymes</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Fluorouracil - administration & dosage</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes</topic><topic>Genetics and Genomics</topic><topic>Genotype & phenotype</topic><topic>Glutathione Transferase - genetics</topic><topic>Humans</topic><topic>Male</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Molecular Medicine</topic><topic>Multivariate analysis</topic><topic>Oncology</topic><topic>Organoplatinum Compounds - administration & dosage</topic><topic>Oxaliplatin</topic><topic>Polymorphism</topic><topic>Polymorphism, Genetic - genetics</topic><topic>Predictive Value of Tests</topic><topic>Proteins - genetics</topic><topic>Retrospective Studies</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - metabolism</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Survival Rate</topic><topic>Thymidylate Synthase - genetics</topic><topic>Time Factors</topic><topic>Toxicity</topic><topic>Transcription Factors</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><topic>X-ray Repair Cross Complementing Protein 1</topic><topic>Xeroderma Pigmentosum Group A Protein</topic><topic>Xeroderma Pigmentosum Group D Protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stoehlmacher, J</creatorcontrib><creatorcontrib>Park, D J</creatorcontrib><creatorcontrib>Zhang, W</creatorcontrib><creatorcontrib>Yang, D</creatorcontrib><creatorcontrib>Groshen, S</creatorcontrib><creatorcontrib>Zahedy, S</creatorcontrib><creatorcontrib>Lenz, H-J</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</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>ProQuest SciTech 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</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>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stoehlmacher, J</au><au>Park, D J</au><au>Zhang, W</au><au>Yang, D</au><au>Groshen, S</au><au>Zahedy, S</au><au>Lenz, H-J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU oxaliplatin combination chemotherapy in refractory colorectal cancer</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2004-07-19</date><risdate>2004</risdate><volume>91</volume><issue>2</issue><spage>344</spage><epage>354</epage><pages>344-354</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>In this marker evaluation study, we tested whether distinct patterns of functional genomic polymorphisms in genes involved in drug metabolic pathways and DNA repair that predict clinical outcome to 5-fluorouracil (5-FU)/oxaliplatin chemotherapy in patients with advanced colorectal cancer could be identified. Functional polymorphisms in DNA-repair genes XPD, ERCC1, XRCC1, XPA, and metabolising genes glutathione
S
-transferase GSTP1, GSTT1, GSTM1, and thymidylate synthase (TS) were assessed retrospectively in 106 patients with refractory stage IV disease who received 5-FU/oxaliplatin combination chemotherapy, using a polymerase chain reaction-based RFLP technique. Favourable genotypes from polymorphisms in XPD-751, ERCC1-118, GSTP1-105, and TS-3′-untranslated region (3′UTR) that are associated with overall survival were identified. After adjustment for performance status, the relative risks of dying for patients who possessed the unfavourable genotype were: 3.33 for XPD-751 (
P
=0.037), 3.25 for GSTP1-105 (
P
=0.072), 2.05 for ERCC1-118 (
P
=0.037), and 1.65 for TS-3′UTR (
P
=0.091) when compared to their respective beneficial genomic variants. Combination analysis with all four polymorphisms revealed that patients possessing ⩾2 favourable genotypes survived a median of 17.4 months (95% confidence interval (CI): 9.4, 26.5) compared to 5.4 months (95% CI: 4.3, 6.0) in patients with no favourable genotype. Patients who carried one favourable genotype demonstrated intermediate survival of 10.2 months (95% CI: 6.8, 15.3;
P
<0.001). Polymorphisms in the TS-3′UTR and GSTP1-105 gene were also associated with time to progression. After adjustment for performance status, patients with an unfavourable TS-3′UTR genotype had a relative risk of disease progression of 1.76 (
P
=0.020) and those with the unfavourable GSTP1-105 genotype showed a relative risk of progression of 2.00 (
P
=0.018). The genomic polymorphisms XPD-751, ERCC1-118, GSTP1-105, and TS-3′UTR may be useful in predicting overall survival and time to progression of colorectal cancer in patients who receive 5-FU/oxaliplatin chemotherapy. These findings require independent prospective confirmation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>15213713</pmid><doi>10.1038/sj.bjc.6601975</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-0920 |
| ispartof | British journal of cancer, 2004-07, Vol.91 (2), p.344-354 |
| issn | 0007-0920 1532-1827 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2409815 |
| source | PubMed Central Free |
| subjects | Acyltransferases - genetics Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Biomarkers, Tumor - genetics Biomedical and Life Sciences Biomedicine Cancer Research Cancer therapies Chemotherapy Clinical outcomes Colorectal cancer Colorectal Neoplasms - drug therapy Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology Disease Progression DNA Helicases DNA Repair DNA-Binding Proteins - genetics Drug Resistance Endonucleases - genetics Enzymes Epidemiology Female Fluorouracil - administration & dosage Gastroenterology. Liver. Pancreas. Abdomen Gene Expression Regulation, Neoplastic Genes Genetics and Genomics Genotype & phenotype Glutathione Transferase - genetics Humans Male Medical research Medical sciences Middle Aged Molecular Medicine Multivariate analysis Oncology Organoplatinum Compounds - administration & dosage Oxaliplatin Polymorphism Polymorphism, Genetic - genetics Predictive Value of Tests Proteins - genetics Retrospective Studies Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - metabolism Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Survival Rate Thymidylate Synthase - genetics Time Factors Toxicity Transcription Factors Treatment Outcome Tumors X-ray Repair Cross Complementing Protein 1 Xeroderma Pigmentosum Group A Protein Xeroderma Pigmentosum Group D Protein |
| title | A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU oxaliplatin combination chemotherapy in refractory colorectal cancer |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T23%3A13%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20multivariate%20analysis%20of%20genomic%20polymorphisms:%20prediction%20of%20clinical%20outcome%20to%205-FU%20oxaliplatin%20combination%20chemotherapy%20in%20refractory%20colorectal%20cancer&rft.jtitle=British%20journal%20of%20cancer&rft.au=Stoehlmacher,%20J&rft.date=2004-07-19&rft.volume=91&rft.issue=2&rft.spage=344&rft.epage=354&rft.pages=344-354&rft.issn=0007-0920&rft.eissn=1532-1827&rft.coden=BJCAAI&rft_id=info:doi/10.1038/sj.bjc.6601975&rft_dat=%3Cproquest_pubme%3E984037701%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c571t-fa6a3b7852eb358ea9a43a0688ea965d2912f55d6fa608fb3ed71d654f441a093%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=229979632&rft_id=info:pmid/15213713&rfr_iscdi=true |