Thymidylate Synthase and Methylenetetrahydrofolate Reductase Gene Polymorphism in Normal Tissue As Predictors of Fluorouracil Sensitivity
To analyze thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with respect to fluorouracil (FU) sensitivity. The study included a retrospective analysis of 88 patients with metastatic colorectal cancer and a prospective trial with 51 patients also with measur...
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| Veröffentlicht in: | Journal of clinical oncology 2005-03, Vol.23 (7), p.1365-1369 |
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| container_title | Journal of clinical oncology |
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| creator | JAKOBSEN, Anders NIELSEN, Jens Nederby GYLDENKERNE, Niels LINDEBERG, Jan |
| description | To analyze thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with respect to fluorouracil (FU) sensitivity.
The study included a retrospective analysis of 88 patients with metastatic colorectal cancer and a prospective trial with 51 patients also with measurable metastases. All patients were treated with FU and leucovorin. The analysis of gene polymorphism was performed on normal intestinal tissue and lymphocytes.
The response rate was significantly higher in patients with TS 3R/3R or MTHFR 677 TT gene polymorphism compared with the other groups. The difference of response rate translated to a difference in time to progression. Similar results were observed in the retrospective analysis and the prospective confirmatory trial.
The analysis of gene polymorphism allows delineation of a group of patients (30%) with a response rate to a single drug of approximately 50%. This information should be used in the design of tailored treatment. |
| doi_str_mv | 10.1200/JCO.2005.06.219 |
| format | Article |
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The study included a retrospective analysis of 88 patients with metastatic colorectal cancer and a prospective trial with 51 patients also with measurable metastases. All patients were treated with FU and leucovorin. The analysis of gene polymorphism was performed on normal intestinal tissue and lymphocytes.
The response rate was significantly higher in patients with TS 3R/3R or MTHFR 677 TT gene polymorphism compared with the other groups. The difference of response rate translated to a difference in time to progression. Similar results were observed in the retrospective analysis and the prospective confirmatory trial.
The analysis of gene polymorphism allows delineation of a group of patients (30%) with a response rate to a single drug of approximately 50%. This information should be used in the design of tailored treatment.</description><identifier>ISSN: 0732-183X</identifier><identifier>EISSN: 1527-7755</identifier><identifier>DOI: 10.1200/JCO.2005.06.219</identifier><identifier>PMID: 15735113</identifier><language>eng</language><publisher>Baltimore, MD: American Society of Clinical Oncology</publisher><subject>Biological and medical sciences ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - genetics ; Disease Progression ; Drug Screening Assays, Antitumor ; Female ; Fluorouracil - therapeutic use ; Humans ; Male ; Medical sciences ; Methylenetetrahydrofolate Reductase (NADPH2) - genetics ; Middle Aged ; Neoplasm Metastasis ; Polymorphism, Genetic ; Prospective Studies ; Retrospective Studies ; Thymidylate Synthase - genetics ; Tumors</subject><ispartof>Journal of clinical oncology, 2005-03, Vol.23 (7), p.1365-1369</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c397t-e0d75e2f18229e36516878a6c74ce9639c77645e79feebcb33ea6bc330b161bf3</citedby><cites>FETCH-LOGICAL-c397t-e0d75e2f18229e36516878a6c74ce9639c77645e79feebcb33ea6bc330b161bf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,3716,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16570475$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15735113$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>JAKOBSEN, Anders</creatorcontrib><creatorcontrib>NIELSEN, Jens Nederby</creatorcontrib><creatorcontrib>GYLDENKERNE, Niels</creatorcontrib><creatorcontrib>LINDEBERG, Jan</creatorcontrib><title>Thymidylate Synthase and Methylenetetrahydrofolate Reductase Gene Polymorphism in Normal Tissue As Predictors of Fluorouracil Sensitivity</title><title>Journal of clinical oncology</title><addtitle>J Clin Oncol</addtitle><description>To analyze thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with respect to fluorouracil (FU) sensitivity.
The study included a retrospective analysis of 88 patients with metastatic colorectal cancer and a prospective trial with 51 patients also with measurable metastases. All patients were treated with FU and leucovorin. The analysis of gene polymorphism was performed on normal intestinal tissue and lymphocytes.
The response rate was significantly higher in patients with TS 3R/3R or MTHFR 677 TT gene polymorphism compared with the other groups. The difference of response rate translated to a difference in time to progression. Similar results were observed in the retrospective analysis and the prospective confirmatory trial.
The analysis of gene polymorphism allows delineation of a group of patients (30%) with a response rate to a single drug of approximately 50%. This information should be used in the design of tailored treatment.</description><subject>Biological and medical sciences</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Disease Progression</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Female</subject><subject>Fluorouracil - therapeutic use</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Methylenetetrahydrofolate Reductase (NADPH2) - genetics</subject><subject>Middle Aged</subject><subject>Neoplasm Metastasis</subject><subject>Polymorphism, Genetic</subject><subject>Prospective Studies</subject><subject>Retrospective Studies</subject><subject>Thymidylate Synthase - genetics</subject><subject>Tumors</subject><issn>0732-183X</issn><issn>1527-7755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMFu1DAQhi0EotuFMzfkC9yytePYTo7ViragQiu6SNwsx5kQV068tR1QHoG3xktX2tN_mG9-zXwIvaNkQ0tCLr5s7zY5-YaITUmbF2hFeSkLKTl_iVZEsrKgNft5hs5jfCSEVjXjr9EZ5ZJxStkK_d0Ny2i7xekE-GGZ0qAjYD11-CukYXEwQYIU9LB0wff-P_YdutmkA3edx_jeu2X0YT_YOGI74W8-jNrhnY1xBnwZ8X2AzprkQ8S-x1du9sHPQRvr8ANM0Sb726blDXrVaxfh7THX6MfVp932pri9u_68vbwtDGtkKoB0kkPZ07osG2CCU1HLWgsjKwONYI2RUlQcZNMDtKZlDLRoDWOkpYK2PVujj8-9--CfZohJjTYacE5P4OeohKyELLOgNbp4Bk3wMQbo1T7YUYdFUaIO9lW2rw72FREq288b74_VcztCd-KPujPw4QjoaLTrg56MjSdOcEkqyU83DvbX8McGUDErdbm2VI_Gl0xJRfPv7B-4ip2f</recordid><startdate>20050301</startdate><enddate>20050301</enddate><creator>JAKOBSEN, Anders</creator><creator>NIELSEN, Jens Nederby</creator><creator>GYLDENKERNE, Niels</creator><creator>LINDEBERG, Jan</creator><general>American Society of Clinical Oncology</general><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>20050301</creationdate><title>Thymidylate Synthase and Methylenetetrahydrofolate Reductase Gene Polymorphism in Normal Tissue As Predictors of Fluorouracil Sensitivity</title><author>JAKOBSEN, Anders ; NIELSEN, Jens Nederby ; GYLDENKERNE, Niels ; LINDEBERG, Jan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c397t-e0d75e2f18229e36516878a6c74ce9639c77645e79feebcb33ea6bc330b161bf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Biological and medical sciences</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Disease Progression</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Female</topic><topic>Fluorouracil - therapeutic use</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Methylenetetrahydrofolate Reductase (NADPH2) - genetics</topic><topic>Middle Aged</topic><topic>Neoplasm Metastasis</topic><topic>Polymorphism, Genetic</topic><topic>Prospective Studies</topic><topic>Retrospective Studies</topic><topic>Thymidylate Synthase - genetics</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>JAKOBSEN, Anders</creatorcontrib><creatorcontrib>NIELSEN, Jens Nederby</creatorcontrib><creatorcontrib>GYLDENKERNE, Niels</creatorcontrib><creatorcontrib>LINDEBERG, Jan</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>MEDLINE - Academic</collection><jtitle>Journal of clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>JAKOBSEN, Anders</au><au>NIELSEN, Jens Nederby</au><au>GYLDENKERNE, Niels</au><au>LINDEBERG, Jan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Thymidylate Synthase and Methylenetetrahydrofolate Reductase Gene Polymorphism in Normal Tissue As Predictors of Fluorouracil Sensitivity</atitle><jtitle>Journal of clinical oncology</jtitle><addtitle>J Clin Oncol</addtitle><date>2005-03-01</date><risdate>2005</risdate><volume>23</volume><issue>7</issue><spage>1365</spage><epage>1369</epage><pages>1365-1369</pages><issn>0732-183X</issn><eissn>1527-7755</eissn><abstract>To analyze thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with respect to fluorouracil (FU) sensitivity.
The study included a retrospective analysis of 88 patients with metastatic colorectal cancer and a prospective trial with 51 patients also with measurable metastases. All patients were treated with FU and leucovorin. The analysis of gene polymorphism was performed on normal intestinal tissue and lymphocytes.
The response rate was significantly higher in patients with TS 3R/3R or MTHFR 677 TT gene polymorphism compared with the other groups. The difference of response rate translated to a difference in time to progression. Similar results were observed in the retrospective analysis and the prospective confirmatory trial.
The analysis of gene polymorphism allows delineation of a group of patients (30%) with a response rate to a single drug of approximately 50%. This information should be used in the design of tailored treatment.</abstract><cop>Baltimore, MD</cop><pub>American Society of Clinical Oncology</pub><pmid>15735113</pmid><doi>10.1200/JCO.2005.06.219</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of clinical oncology, 2005-03, Vol.23 (7), p.1365-1369 |
| issn | 0732-183X 1527-7755 |
| language | eng |
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| source | MEDLINE; American Society of Clinical Oncology Online Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Biological and medical sciences Colorectal Neoplasms - drug therapy Colorectal Neoplasms - genetics Disease Progression Drug Screening Assays, Antitumor Female Fluorouracil - therapeutic use Humans Male Medical sciences Methylenetetrahydrofolate Reductase (NADPH2) - genetics Middle Aged Neoplasm Metastasis Polymorphism, Genetic Prospective Studies Retrospective Studies Thymidylate Synthase - genetics Tumors |
| title | Thymidylate Synthase and Methylenetetrahydrofolate Reductase Gene Polymorphism in Normal Tissue As Predictors of Fluorouracil Sensitivity |
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