Impact of SHMT1 polymorphism on the clinical outcome of patients with metastatic colorectal cancer treated with first-line FOLFIRI + bevacizumab
The impact of thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), and serine hydroxymethyltransferase 1 (SHMT1) gene polymorphisms and that of dihydropyrimidine dehydrogenase (DPD) enzyme activity, serum total homocysteine level, and estimated serum creatinine clearance on firs...
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| Veröffentlicht in: | Pharmacogenetics and genomics 2012, Vol.22 (1), p.69-72 |
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| creator | BUDAI, Barna KOMLOSI, Viktor ADLEFF, Vilmos PAP, Eva RETI, Andrea NAGY, Tünde KRALOVANSZKY, Judit LANG, István HITRE, Erika |
| description | The impact of thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), and serine hydroxymethyltransferase 1 (SHMT1) gene polymorphisms and that of dihydropyrimidine dehydrogenase (DPD) enzyme activity, serum total homocysteine level, and estimated serum creatinine clearance on first-line 5-fluorouracil, leucovorin, irinotecan, and bevacizumab (FOLFIRI+bevacizumab) regimen efficacy in metastatic colorectal cancer patients was investigated. DNA was extracted from peripheral blood mononuclear cells. Genotyping was performed for TYMS 5'UTR variable number tandem repeat, TYMS 3'UTR ins/del, MTHFR C677T, and SHMT1 C1420T polymorphisms. The DPD activity of peripheral blood mononuclear cells was also determined. The univariate and multivariate analyses demonstrated that the SHMT1 1420T allele was associated with better response (P=0.025) and longer progression-free survival (PFS) (P=0.00004) and overall survival (OS) (P=0.034). Grade ≥2 hypertension was also an independent prognostic factor of longer progression-free survival and OS. Bevacizumab-related hypertension might be a predictive marker of treatment efficacy (P=0.0002 for OS) in the case of wild (CC) SHMT1 1420 genotypes only. |
| doi_str_mv | 10.1097/FPC.0b013e32834d8376 |
| format | Article |
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DNA was extracted from peripheral blood mononuclear cells. Genotyping was performed for TYMS 5'UTR variable number tandem repeat, TYMS 3'UTR ins/del, MTHFR C677T, and SHMT1 C1420T polymorphisms. The DPD activity of peripheral blood mononuclear cells was also determined. The univariate and multivariate analyses demonstrated that the SHMT1 1420T allele was associated with better response (P=0.025) and longer progression-free survival (PFS) (P=0.00004) and overall survival (OS) (P=0.034). Grade ≥2 hypertension was also an independent prognostic factor of longer progression-free survival and OS. Bevacizumab-related hypertension might be a predictive marker of treatment efficacy (P=0.0002 for OS) in the case of wild (CC) SHMT1 1420 genotypes only.</description><identifier>ISSN: 1744-6872</identifier><identifier>EISSN: 1744-6880</identifier><identifier>DOI: 10.1097/FPC.0b013e32834d8376</identifier><identifier>PMID: 22044939</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject><![CDATA[3' Untranslated Regions ; 5' Untranslated Regions ; Alleles ; Antibodies, Monoclonal, Humanized - administration & dosage ; Antibodies, Monoclonal, Humanized - adverse effects ; Antibodies, Monoclonal, Humanized - therapeutic use ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Bevacizumab ; Biological and medical sciences ; Camptothecin - administration & dosage ; Camptothecin - adverse effects ; Camptothecin - analogs & derivatives ; Camptothecin - therapeutic use ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - secondary ; Creatinine - blood ; Dihydrouracil Dehydrogenase (NADP) - blood ; Disease-Free Survival ; Fluorouracil - administration & dosage ; Fluorouracil - adverse effects ; Fluorouracil - therapeutic use ; Fundamental and applied biological sciences. Psychology ; Gastroenterology. Liver. Pancreas. Abdomen ; General pharmacology ; Genetic Association Studies ; Glycine Hydroxymethyltransferase - genetics ; Homocysteine - blood ; Humans ; Hypertension - chemically induced ; INDEL Mutation ; Leucovorin - administration & dosage ; Leucovorin - adverse effects ; Leucovorin - therapeutic use ; Medical sciences ; Methylenetetrahydrofolate Reductase (NADPH2) - genetics ; Molecular and cellular biology ; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions ; Pharmacology. Drug treatments ; Polymorphism, Genetic ; Prognosis ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Thymidylate Synthase - genetics ; Treatment Outcome ; Tumors]]></subject><ispartof>Pharmacogenetics and genomics, 2012, Vol.22 (1), p.69-72</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c251t-74d0d73f5de9626b47bc9cf688a48aeef09f2cdd98d571c7de7fa0aaa8ec0c683</citedby><cites>FETCH-LOGICAL-c251t-74d0d73f5de9626b47bc9cf688a48aeef09f2cdd98d571c7de7fa0aaa8ec0c683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4023,27922,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25549157$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22044939$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BUDAI, Barna</creatorcontrib><creatorcontrib>KOMLOSI, Viktor</creatorcontrib><creatorcontrib>ADLEFF, Vilmos</creatorcontrib><creatorcontrib>PAP, Eva</creatorcontrib><creatorcontrib>RETI, Andrea</creatorcontrib><creatorcontrib>NAGY, Tünde</creatorcontrib><creatorcontrib>KRALOVANSZKY, Judit</creatorcontrib><creatorcontrib>LANG, István</creatorcontrib><creatorcontrib>HITRE, Erika</creatorcontrib><title>Impact of SHMT1 polymorphism on the clinical outcome of patients with metastatic colorectal cancer treated with first-line FOLFIRI + bevacizumab</title><title>Pharmacogenetics and genomics</title><addtitle>Pharmacogenet Genomics</addtitle><description>The impact of thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), and serine hydroxymethyltransferase 1 (SHMT1) gene polymorphisms and that of dihydropyrimidine dehydrogenase (DPD) enzyme activity, serum total homocysteine level, and estimated serum creatinine clearance on first-line 5-fluorouracil, leucovorin, irinotecan, and bevacizumab (FOLFIRI+bevacizumab) regimen efficacy in metastatic colorectal cancer patients was investigated. DNA was extracted from peripheral blood mononuclear cells. Genotyping was performed for TYMS 5'UTR variable number tandem repeat, TYMS 3'UTR ins/del, MTHFR C677T, and SHMT1 C1420T polymorphisms. The DPD activity of peripheral blood mononuclear cells was also determined. The univariate and multivariate analyses demonstrated that the SHMT1 1420T allele was associated with better response (P=0.025) and longer progression-free survival (PFS) (P=0.00004) and overall survival (OS) (P=0.034). Grade ≥2 hypertension was also an independent prognostic factor of longer progression-free survival and OS. Bevacizumab-related hypertension might be a predictive marker of treatment efficacy (P=0.0002 for OS) in the case of wild (CC) SHMT1 1420 genotypes only.</description><subject>3' Untranslated Regions</subject><subject>5' Untranslated Regions</subject><subject>Alleles</subject><subject>Antibodies, Monoclonal, Humanized - administration & dosage</subject><subject>Antibodies, Monoclonal, Humanized - adverse effects</subject><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Bevacizumab</subject><subject>Biological and medical sciences</subject><subject>Camptothecin - administration & dosage</subject><subject>Camptothecin - adverse effects</subject><subject>Camptothecin - analogs & derivatives</subject><subject>Camptothecin - therapeutic use</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - secondary</subject><subject>Creatinine - blood</subject><subject>Dihydrouracil Dehydrogenase (NADP) - blood</subject><subject>Disease-Free Survival</subject><subject>Fluorouracil - administration & dosage</subject><subject>Fluorouracil - adverse effects</subject><subject>Fluorouracil - therapeutic use</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>General pharmacology</subject><subject>Genetic Association Studies</subject><subject>Glycine Hydroxymethyltransferase - genetics</subject><subject>Homocysteine - blood</subject><subject>Humans</subject><subject>Hypertension - chemically induced</subject><subject>INDEL Mutation</subject><subject>Leucovorin - administration & dosage</subject><subject>Leucovorin - adverse effects</subject><subject>Leucovorin - therapeutic use</subject><subject>Medical sciences</subject><subject>Methylenetetrahydrofolate Reductase (NADPH2) - genetics</subject><subject>Molecular and cellular biology</subject><subject>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</subject><subject>Pharmacology. Drug treatments</subject><subject>Polymorphism, Genetic</subject><subject>Prognosis</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Thymidylate Synthase - genetics</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><issn>1744-6872</issn><issn>1744-6880</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkcFu1DAQhiMEoqXwBgj5gjigFDt24viIVixdaVERlHPkjMdaozgOtlNUnoJHxtUuReI0o9H3z2j-v6peMnrJqJLvtp83l3SkjCNvei5Mz2X3qDpnUoi663v6-KGXzVn1LKXvlPJOieZpddY0VAjF1Xn1e-cXDZkES75efbphZAnTnQ9xObjkSZhJPiCByc0O9ETCmiF4vKcXnR3OOZGfLh-Ix6xTLiMgEKYQEXLBQc-AkeSIOqM5ktbFlOuyEMn2er_dfdmRt2TEWw3u1-r1-Lx6YvWU8MWpXlTfth9uNlf1_vrjbvN-X0PTslxLYaiR3LYGVdd0o5AjKLDlcS16jWipsg0Yo3rTSgbSoLSaaq17BApdzy-qN8e9Sww_Vkx58C4BTpOeMaxpUIwpLlWrCimOJMSQUkQ7LNF5He8GRof7KIYSxfB_FEX26nRgHT2aB9Ff7wvw-gToVMy1sbjl0j-ubYVireR_AHWVlV0</recordid><startdate>2012</startdate><enddate>2012</enddate><creator>BUDAI, Barna</creator><creator>KOMLOSI, Viktor</creator><creator>ADLEFF, Vilmos</creator><creator>PAP, Eva</creator><creator>RETI, Andrea</creator><creator>NAGY, Tünde</creator><creator>KRALOVANSZKY, Judit</creator><creator>LANG, István</creator><creator>HITRE, Erika</creator><general>Lippincott Williams & Wilkins</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>7X8</scope></search><sort><creationdate>2012</creationdate><title>Impact of SHMT1 polymorphism on the clinical outcome of patients with metastatic colorectal cancer treated with first-line FOLFIRI + bevacizumab</title><author>BUDAI, Barna ; KOMLOSI, Viktor ; ADLEFF, Vilmos ; PAP, Eva ; RETI, Andrea ; NAGY, Tünde ; KRALOVANSZKY, Judit ; LANG, István ; HITRE, Erika</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c251t-74d0d73f5de9626b47bc9cf688a48aeef09f2cdd98d571c7de7fa0aaa8ec0c683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>3' Untranslated Regions</topic><topic>5' Untranslated Regions</topic><topic>Alleles</topic><topic>Antibodies, Monoclonal, Humanized - administration & dosage</topic><topic>Antibodies, Monoclonal, Humanized - adverse effects</topic><topic>Antibodies, Monoclonal, Humanized - therapeutic use</topic><topic>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols - adverse effects</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Bevacizumab</topic><topic>Biological and medical sciences</topic><topic>Camptothecin - administration & dosage</topic><topic>Camptothecin - adverse effects</topic><topic>Camptothecin - analogs & derivatives</topic><topic>Camptothecin - therapeutic use</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - secondary</topic><topic>Creatinine - blood</topic><topic>Dihydrouracil Dehydrogenase (NADP) - blood</topic><topic>Disease-Free Survival</topic><topic>Fluorouracil - administration & dosage</topic><topic>Fluorouracil - adverse effects</topic><topic>Fluorouracil - therapeutic use</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>General pharmacology</topic><topic>Genetic Association Studies</topic><topic>Glycine Hydroxymethyltransferase - genetics</topic><topic>Homocysteine - blood</topic><topic>Humans</topic><topic>Hypertension - chemically induced</topic><topic>INDEL Mutation</topic><topic>Leucovorin - administration & dosage</topic><topic>Leucovorin - adverse effects</topic><topic>Leucovorin - therapeutic use</topic><topic>Medical sciences</topic><topic>Methylenetetrahydrofolate Reductase (NADPH2) - genetics</topic><topic>Molecular and cellular biology</topic><topic>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</topic><topic>Pharmacology. Drug treatments</topic><topic>Polymorphism, Genetic</topic><topic>Prognosis</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. 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DNA was extracted from peripheral blood mononuclear cells. Genotyping was performed for TYMS 5'UTR variable number tandem repeat, TYMS 3'UTR ins/del, MTHFR C677T, and SHMT1 C1420T polymorphisms. The DPD activity of peripheral blood mononuclear cells was also determined. The univariate and multivariate analyses demonstrated that the SHMT1 1420T allele was associated with better response (P=0.025) and longer progression-free survival (PFS) (P=0.00004) and overall survival (OS) (P=0.034). Grade ≥2 hypertension was also an independent prognostic factor of longer progression-free survival and OS. Bevacizumab-related hypertension might be a predictive marker of treatment efficacy (P=0.0002 for OS) in the case of wild (CC) SHMT1 1420 genotypes only.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>22044939</pmid><doi>10.1097/FPC.0b013e32834d8376</doi><tpages>4</tpages></addata></record> |
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| identifier | ISSN: 1744-6872 |
| ispartof | Pharmacogenetics and genomics, 2012, Vol.22 (1), p.69-72 |
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| language | eng |
| recordid | cdi_proquest_miscellaneous_911937959 |
| source | MEDLINE; Journals@Ovid Complete |
| subjects | 3' Untranslated Regions 5' Untranslated Regions Alleles Antibodies, Monoclonal, Humanized - administration & dosage Antibodies, Monoclonal, Humanized - adverse effects Antibodies, Monoclonal, Humanized - therapeutic use Antineoplastic Combined Chemotherapy Protocols - administration & dosage Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - therapeutic use Bevacizumab Biological and medical sciences Camptothecin - administration & dosage Camptothecin - adverse effects Camptothecin - analogs & derivatives Camptothecin - therapeutic use Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Colorectal Neoplasms - drug therapy Colorectal Neoplasms - genetics Colorectal Neoplasms - secondary Creatinine - blood Dihydrouracil Dehydrogenase (NADP) - blood Disease-Free Survival Fluorouracil - administration & dosage Fluorouracil - adverse effects Fluorouracil - therapeutic use Fundamental and applied biological sciences. Psychology Gastroenterology. Liver. Pancreas. Abdomen General pharmacology Genetic Association Studies Glycine Hydroxymethyltransferase - genetics Homocysteine - blood Humans Hypertension - chemically induced INDEL Mutation Leucovorin - administration & dosage Leucovorin - adverse effects Leucovorin - therapeutic use Medical sciences Methylenetetrahydrofolate Reductase (NADPH2) - genetics Molecular and cellular biology Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions Pharmacology. Drug treatments Polymorphism, Genetic Prognosis Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Thymidylate Synthase - genetics Treatment Outcome Tumors |
| title | Impact of SHMT1 polymorphism on the clinical outcome of patients with metastatic colorectal cancer treated with first-line FOLFIRI + bevacizumab |
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