Pharmacogenetic Angiogenesis Profiling for First-line Bevacizumab plus Oxaliplatin-Based Chemotherapy in Patients with Metastatic Colorectal Cancer
There is substantial germline genetic variability within angiogenesis pathway genes, thereby causing interindividual differences in angiogenic capacity and resistance to antiangiogenesis therapy. We investigated germline polymorphisms in genes involved in VEGF-dependent and -independent angiogenesis...
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| Veröffentlicht in: | Clinical cancer research 2011-09, Vol.17 (17), p.5783-5792 |
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| creator | GERGER, Armin EL-KHOUEIRY, Anthony BENHAIM, Leonor PAEZ, David EL-KHOUEIRY, Rita ABSENGER, Gudrun LENZ, Heinz-Josef WU ZHANG DONGYUN YANG SINGH, Harpreet BOHANES, Pierre YAN NING WINDER, Thomas LABONTE, Melissa J WILSON, Peter M |
| description | There is substantial germline genetic variability within angiogenesis pathway genes, thereby causing interindividual differences in angiogenic capacity and resistance to antiangiogenesis therapy. We investigated germline polymorphisms in genes involved in VEGF-dependent and -independent angiogenesis pathways to predict clinical outcome and tumor response in metastatic colorectal cancer (mCRC) patients treated with bevacizumab and oxaliplatin-based chemotherapy.
A total of 132 patients treated with first-line bevacizumab and FOLFOX or XELOX were included in this study. Genomic DNA was isolated from whole-blood samples by PCR-RFLP or direct DNA sequencing. The endpoints of the study were progression-free survival (PFS), overall survival (OS), and response rate (RR).
The minor alleles of EGF rs444903 A>G and IGF-1 rs6220 A>G were associated with increased OS and remained significant in multivariate Cox regression analysis (HR: 0.52; 95% CI: 0.31-0.87; adjusted P = 0.012 and HR: 0.60; 95% CI: 0.36-0.99; adjusted P = 0.046, respectively). The minor allele of HIF1α rs11549465 C>T was significantly associated with increased PFS but lost its significance in multivariate analysis. CXCR1 rs2234671 G>C, CXCR2 rs2230054 T>C, EGFR rs2227983 G>A, and VEGFR-2 rs2305948 C>T predicted tumor response, with CXCR1 rs2234671 G>C remaining significant in multiple testing (P(act) = 0.003).
In this study, we identified common germline variants in VEGF-dependent and -independent angiogenesis genes predicting clinical outcome and tumor response in patients with mCRC receiving first-line bevacizumab and oxaliplatin-based chemotherapy. |
| doi_str_mv | 10.1158/1078-0432.CCR-11-1115 |
| format | Article |
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A total of 132 patients treated with first-line bevacizumab and FOLFOX or XELOX were included in this study. Genomic DNA was isolated from whole-blood samples by PCR-RFLP or direct DNA sequencing. The endpoints of the study were progression-free survival (PFS), overall survival (OS), and response rate (RR).
The minor alleles of EGF rs444903 A>G and IGF-1 rs6220 A>G were associated with increased OS and remained significant in multivariate Cox regression analysis (HR: 0.52; 95% CI: 0.31-0.87; adjusted P = 0.012 and HR: 0.60; 95% CI: 0.36-0.99; adjusted P = 0.046, respectively). The minor allele of HIF1α rs11549465 C>T was significantly associated with increased PFS but lost its significance in multivariate analysis. CXCR1 rs2234671 G>C, CXCR2 rs2230054 T>C, EGFR rs2227983 G>A, and VEGFR-2 rs2305948 C>T predicted tumor response, with CXCR1 rs2234671 G>C remaining significant in multiple testing (P(act) = 0.003).
In this study, we identified common germline variants in VEGF-dependent and -independent angiogenesis genes predicting clinical outcome and tumor response in patients with mCRC receiving first-line bevacizumab and oxaliplatin-based chemotherapy.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-11-1115</identifier><identifier>PMID: 21791631</identifier><identifier>CODEN: CCREF4</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Alleles ; Angiogenesis Inhibitors - administration & dosage ; Angiogenesis Inhibitors - pharmacology ; Angiogenesis Inhibitors - therapeutic use ; Antibodies, Monoclonal, Humanized - administration & dosage ; Antineoplastic agents ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Bevacizumab ; Biological and medical sciences ; Chemokines - genetics ; Colorectal Neoplasms - blood supply ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - genetics ; Cytokines - genetics ; Deoxycytidine - analogs & derivatives ; Deoxycytidine - therapeutic use ; Disease-Free Survival ; Female ; Fluorouracil - analogs & derivatives ; Fluorouracil - therapeutic use ; Gastroenterology. Liver. Pancreas. Abdomen ; Genetic Variation ; Genotype ; Humans ; Leucovorin - therapeutic use ; Male ; Medical sciences ; Middle Aged ; Neovascularization, Pathologic - drug therapy ; Neovascularization, Pathologic - genetics ; Organoplatinum Compounds - administration & dosage ; Organoplatinum Compounds - therapeutic use ; Pharmacogenetics ; Pharmacology. Drug treatments ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Tumors ; Vascular Endothelial Growth Factor A - genetics</subject><ispartof>Clinical cancer research, 2011-09, Vol.17 (17), p.5783-5792</ispartof><rights>2015 INIST-CNRS</rights><rights>2011 AACR.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-d0bc98faf29fe56d997028557333bb18c6ae7e80a494ad05f6cd5ebfd704b0b03</citedby><cites>FETCH-LOGICAL-c440t-d0bc98faf29fe56d997028557333bb18c6ae7e80a494ad05f6cd5ebfd704b0b03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3347,27915,27916</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24533241$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21791631$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GERGER, Armin</creatorcontrib><creatorcontrib>EL-KHOUEIRY, Anthony</creatorcontrib><creatorcontrib>BENHAIM, Leonor</creatorcontrib><creatorcontrib>PAEZ, David</creatorcontrib><creatorcontrib>EL-KHOUEIRY, Rita</creatorcontrib><creatorcontrib>ABSENGER, Gudrun</creatorcontrib><creatorcontrib>LENZ, Heinz-Josef</creatorcontrib><creatorcontrib>WU ZHANG</creatorcontrib><creatorcontrib>DONGYUN YANG</creatorcontrib><creatorcontrib>SINGH, Harpreet</creatorcontrib><creatorcontrib>BOHANES, Pierre</creatorcontrib><creatorcontrib>YAN NING</creatorcontrib><creatorcontrib>WINDER, Thomas</creatorcontrib><creatorcontrib>LABONTE, Melissa J</creatorcontrib><creatorcontrib>WILSON, Peter M</creatorcontrib><title>Pharmacogenetic Angiogenesis Profiling for First-line Bevacizumab plus Oxaliplatin-Based Chemotherapy in Patients with Metastatic Colorectal Cancer</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>There is substantial germline genetic variability within angiogenesis pathway genes, thereby causing interindividual differences in angiogenic capacity and resistance to antiangiogenesis therapy. We investigated germline polymorphisms in genes involved in VEGF-dependent and -independent angiogenesis pathways to predict clinical outcome and tumor response in metastatic colorectal cancer (mCRC) patients treated with bevacizumab and oxaliplatin-based chemotherapy.
A total of 132 patients treated with first-line bevacizumab and FOLFOX or XELOX were included in this study. Genomic DNA was isolated from whole-blood samples by PCR-RFLP or direct DNA sequencing. The endpoints of the study were progression-free survival (PFS), overall survival (OS), and response rate (RR).
The minor alleles of EGF rs444903 A>G and IGF-1 rs6220 A>G were associated with increased OS and remained significant in multivariate Cox regression analysis (HR: 0.52; 95% CI: 0.31-0.87; adjusted P = 0.012 and HR: 0.60; 95% CI: 0.36-0.99; adjusted P = 0.046, respectively). The minor allele of HIF1α rs11549465 C>T was significantly associated with increased PFS but lost its significance in multivariate analysis. CXCR1 rs2234671 G>C, CXCR2 rs2230054 T>C, EGFR rs2227983 G>A, and VEGFR-2 rs2305948 C>T predicted tumor response, with CXCR1 rs2234671 G>C remaining significant in multiple testing (P(act) = 0.003).
In this study, we identified common germline variants in VEGF-dependent and -independent angiogenesis genes predicting clinical outcome and tumor response in patients with mCRC receiving first-line bevacizumab and oxaliplatin-based chemotherapy.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alleles</subject><subject>Angiogenesis Inhibitors - administration & dosage</subject><subject>Angiogenesis Inhibitors - pharmacology</subject><subject>Angiogenesis Inhibitors - therapeutic use</subject><subject>Antibodies, Monoclonal, Humanized - administration & dosage</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Bevacizumab</subject><subject>Biological and medical sciences</subject><subject>Chemokines - genetics</subject><subject>Colorectal Neoplasms - blood supply</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Cytokines - genetics</subject><subject>Deoxycytidine - analogs & derivatives</subject><subject>Deoxycytidine - therapeutic use</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Fluorouracil - analogs & derivatives</subject><subject>Fluorouracil - therapeutic use</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Genetic Variation</subject><subject>Genotype</subject><subject>Humans</subject><subject>Leucovorin - therapeutic use</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neovascularization, Pathologic - drug therapy</subject><subject>Neovascularization, Pathologic - genetics</subject><subject>Organoplatinum Compounds - administration & dosage</subject><subject>Organoplatinum Compounds - therapeutic use</subject><subject>Pharmacogenetics</subject><subject>Pharmacology. Drug treatments</subject><subject>Polymorphism, Restriction Fragment Length</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Tumors</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkVtvFiEQhonR2Fr9CRpuvNwKC-zhxqTdWDWp6Rej12SWHb7FsIcAX7X-Df-wrD2oCQkM874zAw8hLzk75Vw1bzirm4JJUZ523eeC87y4ekSOuVJ1IcpKPc7ne80ReRbjN8a45Ew-JUclr1teCX5Mfu1GCBOYZY8zJmfo2bx3f4LoIt2FxTrv5j21S6AXLsRU5BDpOV6DcT8PE_R09YdIr36Ad6uH5ObiHCIOtBtxWtKIAdYb6ma6yzmcU6TfXRrpJ0wQE2wdu8UvAU0CTzuYDYbn5IkFH_HF3X5Cvl68-9J9KC6v3n_szi4LIyVLxcB60zYWbNlaVNXQtjUrm_x8IUTf88ZUgDU2DGQrYWDKVmZQ2NuhZrJnPRMn5O1t3fXQTziYPF0Ar9fgJgg3egGn_8_MbtT75VoLXstGNrmAui1gwhJjQPvg5UxvlPRGQG8EdKaUr_RGKfte_dv4wXWPJQte3wkgGvA25H9x8a9OKiFKycVv6gigVA</recordid><startdate>20110901</startdate><enddate>20110901</enddate><creator>GERGER, Armin</creator><creator>EL-KHOUEIRY, Anthony</creator><creator>BENHAIM, Leonor</creator><creator>PAEZ, David</creator><creator>EL-KHOUEIRY, Rita</creator><creator>ABSENGER, Gudrun</creator><creator>LENZ, Heinz-Josef</creator><creator>WU ZHANG</creator><creator>DONGYUN YANG</creator><creator>SINGH, Harpreet</creator><creator>BOHANES, Pierre</creator><creator>YAN NING</creator><creator>WINDER, Thomas</creator><creator>LABONTE, Melissa J</creator><creator>WILSON, Peter M</creator><general>American Association for Cancer Research</general><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>5PM</scope></search><sort><creationdate>20110901</creationdate><title>Pharmacogenetic Angiogenesis Profiling for First-line Bevacizumab plus Oxaliplatin-Based Chemotherapy in Patients with Metastatic Colorectal Cancer</title><author>GERGER, Armin ; EL-KHOUEIRY, Anthony ; BENHAIM, Leonor ; PAEZ, David ; EL-KHOUEIRY, Rita ; ABSENGER, Gudrun ; LENZ, Heinz-Josef ; WU ZHANG ; DONGYUN YANG ; SINGH, Harpreet ; BOHANES, Pierre ; YAN NING ; WINDER, Thomas ; LABONTE, Melissa J ; WILSON, Peter M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-d0bc98faf29fe56d997028557333bb18c6ae7e80a494ad05f6cd5ebfd704b0b03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alleles</topic><topic>Angiogenesis Inhibitors - administration & dosage</topic><topic>Angiogenesis Inhibitors - pharmacology</topic><topic>Angiogenesis Inhibitors - therapeutic use</topic><topic>Antibodies, Monoclonal, Humanized - administration & dosage</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Bevacizumab</topic><topic>Biological and medical sciences</topic><topic>Chemokines - genetics</topic><topic>Colorectal Neoplasms - blood supply</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Cytokines - genetics</topic><topic>Deoxycytidine - analogs & derivatives</topic><topic>Deoxycytidine - therapeutic use</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Fluorouracil - analogs & derivatives</topic><topic>Fluorouracil - therapeutic use</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Genetic Variation</topic><topic>Genotype</topic><topic>Humans</topic><topic>Leucovorin - therapeutic use</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neovascularization, Pathologic - drug therapy</topic><topic>Neovascularization, Pathologic - genetics</topic><topic>Organoplatinum Compounds - administration & dosage</topic><topic>Organoplatinum Compounds - therapeutic use</topic><topic>Pharmacogenetics</topic><topic>Pharmacology. Drug treatments</topic><topic>Polymorphism, Restriction Fragment Length</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Tumors</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GERGER, Armin</creatorcontrib><creatorcontrib>EL-KHOUEIRY, Anthony</creatorcontrib><creatorcontrib>BENHAIM, Leonor</creatorcontrib><creatorcontrib>PAEZ, David</creatorcontrib><creatorcontrib>EL-KHOUEIRY, Rita</creatorcontrib><creatorcontrib>ABSENGER, Gudrun</creatorcontrib><creatorcontrib>LENZ, Heinz-Josef</creatorcontrib><creatorcontrib>WU ZHANG</creatorcontrib><creatorcontrib>DONGYUN YANG</creatorcontrib><creatorcontrib>SINGH, Harpreet</creatorcontrib><creatorcontrib>BOHANES, Pierre</creatorcontrib><creatorcontrib>YAN NING</creatorcontrib><creatorcontrib>WINDER, Thomas</creatorcontrib><creatorcontrib>LABONTE, Melissa J</creatorcontrib><creatorcontrib>WILSON, Peter M</creatorcontrib><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>PubMed Central (Full Participant titles)</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GERGER, Armin</au><au>EL-KHOUEIRY, Anthony</au><au>BENHAIM, Leonor</au><au>PAEZ, David</au><au>EL-KHOUEIRY, Rita</au><au>ABSENGER, Gudrun</au><au>LENZ, Heinz-Josef</au><au>WU ZHANG</au><au>DONGYUN YANG</au><au>SINGH, Harpreet</au><au>BOHANES, Pierre</au><au>YAN NING</au><au>WINDER, Thomas</au><au>LABONTE, Melissa J</au><au>WILSON, Peter M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacogenetic Angiogenesis Profiling for First-line Bevacizumab plus Oxaliplatin-Based Chemotherapy in Patients with Metastatic Colorectal Cancer</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2011-09-01</date><risdate>2011</risdate><volume>17</volume><issue>17</issue><spage>5783</spage><epage>5792</epage><pages>5783-5792</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><coden>CCREF4</coden><abstract>There is substantial germline genetic variability within angiogenesis pathway genes, thereby causing interindividual differences in angiogenic capacity and resistance to antiangiogenesis therapy. We investigated germline polymorphisms in genes involved in VEGF-dependent and -independent angiogenesis pathways to predict clinical outcome and tumor response in metastatic colorectal cancer (mCRC) patients treated with bevacizumab and oxaliplatin-based chemotherapy.
A total of 132 patients treated with first-line bevacizumab and FOLFOX or XELOX were included in this study. Genomic DNA was isolated from whole-blood samples by PCR-RFLP or direct DNA sequencing. The endpoints of the study were progression-free survival (PFS), overall survival (OS), and response rate (RR).
The minor alleles of EGF rs444903 A>G and IGF-1 rs6220 A>G were associated with increased OS and remained significant in multivariate Cox regression analysis (HR: 0.52; 95% CI: 0.31-0.87; adjusted P = 0.012 and HR: 0.60; 95% CI: 0.36-0.99; adjusted P = 0.046, respectively). The minor allele of HIF1α rs11549465 C>T was significantly associated with increased PFS but lost its significance in multivariate analysis. CXCR1 rs2234671 G>C, CXCR2 rs2230054 T>C, EGFR rs2227983 G>A, and VEGFR-2 rs2305948 C>T predicted tumor response, with CXCR1 rs2234671 G>C remaining significant in multiple testing (P(act) = 0.003).
In this study, we identified common germline variants in VEGF-dependent and -independent angiogenesis genes predicting clinical outcome and tumor response in patients with mCRC receiving first-line bevacizumab and oxaliplatin-based chemotherapy.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>21791631</pmid><doi>10.1158/1078-0432.CCR-11-1115</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical cancer research, 2011-09, Vol.17 (17), p.5783-5792 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research; Alma/SFX Local Collection |
| subjects | Adult Aged Aged, 80 and over Alleles Angiogenesis Inhibitors - administration & dosage Angiogenesis Inhibitors - pharmacology Angiogenesis Inhibitors - therapeutic use Antibodies, Monoclonal, Humanized - administration & dosage Antineoplastic agents Antineoplastic Combined Chemotherapy Protocols - therapeutic use Bevacizumab Biological and medical sciences Chemokines - genetics Colorectal Neoplasms - blood supply Colorectal Neoplasms - drug therapy Colorectal Neoplasms - genetics Cytokines - genetics Deoxycytidine - analogs & derivatives Deoxycytidine - therapeutic use Disease-Free Survival Female Fluorouracil - analogs & derivatives Fluorouracil - therapeutic use Gastroenterology. Liver. Pancreas. Abdomen Genetic Variation Genotype Humans Leucovorin - therapeutic use Male Medical sciences Middle Aged Neovascularization, Pathologic - drug therapy Neovascularization, Pathologic - genetics Organoplatinum Compounds - administration & dosage Organoplatinum Compounds - therapeutic use Pharmacogenetics Pharmacology. Drug treatments Polymorphism, Restriction Fragment Length Polymorphism, Single Nucleotide Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Tumors Vascular Endothelial Growth Factor A - genetics |
| title | Pharmacogenetic Angiogenesis Profiling for First-line Bevacizumab plus Oxaliplatin-Based Chemotherapy in Patients with Metastatic Colorectal Cancer |
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