Polymorphisms of the ribonucleotide reductase M1 gene and sensitivity to platin-based chemotherapy in non-small cell lung cancer

Abstract Ribonucleotide reductase catalyzes the rate limiting step of deoxyribonucleotide formation, a crucially important step in DNA synthesis and repair. The regulatory subunit M1 of ribonucleotide reductase (RRM1) is the necessary part of the RR function and controls substrate specificity and gl...

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Veröffentlicht in:Lung cancer (Amsterdam, Netherlands) Netherlands), 2009-12, Vol.66 (3), p.344-349
Hauptverfasser: Feng, Ji-feng, Wu, Jian-zhong, Hu, Sai-nan, Gao, Chang-ming, Shi, Mei-qi, Lu, Zhu-hong, Sun, Xin-chen, Zhou, Jin-Rong, Chen, Bao-an
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container_issue 3
container_start_page 344
container_title Lung cancer (Amsterdam, Netherlands)
container_volume 66
creator Feng, Ji-feng
Wu, Jian-zhong
Hu, Sai-nan
Gao, Chang-ming
Shi, Mei-qi
Lu, Zhu-hong
Sun, Xin-chen
Zhou, Jin-Rong
Chen, Bao-an
description Abstract Ribonucleotide reductase catalyzes the rate limiting step of deoxyribonucleotide formation, a crucially important step in DNA synthesis and repair. The regulatory subunit M1 of ribonucleotide reductase (RRM1) is the necessary part of the RR function and controls substrate specificity and global on/off enzyme activity. Despite recent research progress, the role of RRM1 in lung cancer sensitivity to chemotherapeutics remains to be elucidated. This study was to investigate the relationship between polymorphisms of the RRM1 gene and sensitivity to platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Genomic DNA samples from 214 NSCLC patients treated with platinum-based chemotherapy were used to determine the RRM1 promoter allelotypes. The RR37CC-RR524TT was the most frequent allelotype (38.50%), followed by RR37AC-RR524CT (26.76%) and RR37CC-RR524CT (14.95%). The average response rate for chemotherapy was 44.4%. The response rates to the treatment regimens in the RR37CC-RR524TT, RR37AC-RR524CT and RR37CC-RR524CT allelotypes were 43.9%, 52.6%, and 51.6%, respectively. The response rates to therapy among patients with RRM1 (−)524 allelotypes were significantly different ( p = 0.046), whereas that among patients with RRM1 (−)37 allelotypes were not significant. Further analysis showed that the response rate in the patients with RR524CT allelotype (52.3%) was the highest, compared with that with RR37CC-RR524TT allelotype (43.9%, p = 0.28), or the Others (RR524CC and RR37AC-RR524TT, 30.2%, p = 0.02). Our results suggest that the RR524CT allelotype may be associated with an increased sensitivity to platinum-based chemotherapy in NSCLC. Further research on determining RR524CT as a clinical marker for predicting response to platinum-based therapy in NSCLC patients is warranted.
doi_str_mv 10.1016/j.lungcan.2009.02.015
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The regulatory subunit M1 of ribonucleotide reductase (RRM1) is the necessary part of the RR function and controls substrate specificity and global on/off enzyme activity. Despite recent research progress, the role of RRM1 in lung cancer sensitivity to chemotherapeutics remains to be elucidated. This study was to investigate the relationship between polymorphisms of the RRM1 gene and sensitivity to platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Genomic DNA samples from 214 NSCLC patients treated with platinum-based chemotherapy were used to determine the RRM1 promoter allelotypes. The RR37CC-RR524TT was the most frequent allelotype (38.50%), followed by RR37AC-RR524CT (26.76%) and RR37CC-RR524CT (14.95%). The average response rate for chemotherapy was 44.4%. The response rates to the treatment regimens in the RR37CC-RR524TT, RR37AC-RR524CT and RR37CC-RR524CT allelotypes were 43.9%, 52.6%, and 51.6%, respectively. The response rates to therapy among patients with RRM1 (−)524 allelotypes were significantly different ( p = 0.046), whereas that among patients with RRM1 (−)37 allelotypes were not significant. Further analysis showed that the response rate in the patients with RR524CT allelotype (52.3%) was the highest, compared with that with RR37CC-RR524TT allelotype (43.9%, p = 0.28), or the Others (RR524CC and RR37AC-RR524TT, 30.2%, p = 0.02). Our results suggest that the RR524CT allelotype may be associated with an increased sensitivity to platinum-based chemotherapy in NSCLC. Further research on determining RR524CT as a clinical marker for predicting response to platinum-based therapy in NSCLC patients is warranted.</description><identifier>ISSN: 0169-5002</identifier><identifier>EISSN: 1872-8332</identifier><identifier>DOI: 10.1016/j.lungcan.2009.02.015</identifier><identifier>PMID: 19304340</identifier><identifier>CODEN: LUCAE5</identifier><language>eng</language><publisher>Oxford: Elsevier Ireland Ltd</publisher><subject>Adult ; Aged ; Biological and medical sciences ; Biomarkers, Pharmacological - metabolism ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - pathology ; Chemotherapy ; Drug Resistance, Neoplasm - genetics ; Female ; Genetic polymorphism ; Genetic Testing ; Hematology, Oncology and Palliative Medicine ; Humans ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Lung Neoplasms - pathology ; Male ; Medical sciences ; Middle Aged ; Neoplasm Staging ; Non-small cell lung cancer ; Platinum ; Platinum Compounds - therapeutic use ; Pneumology ; Polymorphism, Genetic ; Pulmonary/Respiratory ; RRM1 ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - metabolism ; Tumors ; Tumors of the respiratory system and mediastinum</subject><ispartof>Lung cancer (Amsterdam, Netherlands), 2009-12, Vol.66 (3), p.344-349</ispartof><rights>2009</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c449t-74a7104b878e1ffdc382bbebd15f97050e9c2724630ea4eeffdec80ee7c872193</citedby><cites>FETCH-LOGICAL-c449t-74a7104b878e1ffdc382bbebd15f97050e9c2724630ea4eeffdec80ee7c872193</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.lungcan.2009.02.015$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=22153557$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19304340$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Feng, Ji-feng</creatorcontrib><creatorcontrib>Wu, Jian-zhong</creatorcontrib><creatorcontrib>Hu, Sai-nan</creatorcontrib><creatorcontrib>Gao, Chang-ming</creatorcontrib><creatorcontrib>Shi, Mei-qi</creatorcontrib><creatorcontrib>Lu, Zhu-hong</creatorcontrib><creatorcontrib>Sun, Xin-chen</creatorcontrib><creatorcontrib>Zhou, Jin-Rong</creatorcontrib><creatorcontrib>Chen, Bao-an</creatorcontrib><title>Polymorphisms of the ribonucleotide reductase M1 gene and sensitivity to platin-based chemotherapy in non-small cell lung cancer</title><title>Lung cancer (Amsterdam, Netherlands)</title><addtitle>Lung Cancer</addtitle><description>Abstract Ribonucleotide reductase catalyzes the rate limiting step of deoxyribonucleotide formation, a crucially important step in DNA synthesis and repair. The regulatory subunit M1 of ribonucleotide reductase (RRM1) is the necessary part of the RR function and controls substrate specificity and global on/off enzyme activity. Despite recent research progress, the role of RRM1 in lung cancer sensitivity to chemotherapeutics remains to be elucidated. This study was to investigate the relationship between polymorphisms of the RRM1 gene and sensitivity to platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Genomic DNA samples from 214 NSCLC patients treated with platinum-based chemotherapy were used to determine the RRM1 promoter allelotypes. The RR37CC-RR524TT was the most frequent allelotype (38.50%), followed by RR37AC-RR524CT (26.76%) and RR37CC-RR524CT (14.95%). The average response rate for chemotherapy was 44.4%. The response rates to the treatment regimens in the RR37CC-RR524TT, RR37AC-RR524CT and RR37CC-RR524CT allelotypes were 43.9%, 52.6%, and 51.6%, respectively. The response rates to therapy among patients with RRM1 (−)524 allelotypes were significantly different ( p = 0.046), whereas that among patients with RRM1 (−)37 allelotypes were not significant. Further analysis showed that the response rate in the patients with RR524CT allelotype (52.3%) was the highest, compared with that with RR37CC-RR524TT allelotype (43.9%, p = 0.28), or the Others (RR524CC and RR37AC-RR524TT, 30.2%, p = 0.02). Our results suggest that the RR524CT allelotype may be associated with an increased sensitivity to platinum-based chemotherapy in NSCLC. 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Wu, Jian-zhong ; Hu, Sai-nan ; Gao, Chang-ming ; Shi, Mei-qi ; Lu, Zhu-hong ; Sun, Xin-chen ; Zhou, Jin-Rong ; Chen, Bao-an</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c449t-74a7104b878e1ffdc382bbebd15f97050e9c2724630ea4eeffdec80ee7c872193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Pharmacological - metabolism</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Chemotherapy</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Female</topic><topic>Genetic polymorphism</topic><topic>Genetic Testing</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Non-small cell lung cancer</topic><topic>Platinum</topic><topic>Platinum Compounds - therapeutic use</topic><topic>Pneumology</topic><topic>Polymorphism, Genetic</topic><topic>Pulmonary/Respiratory</topic><topic>RRM1</topic><topic>Tumor Suppressor Proteins - genetics</topic><topic>Tumor Suppressor Proteins - metabolism</topic><topic>Tumors</topic><topic>Tumors of the respiratory system and mediastinum</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Feng, Ji-feng</creatorcontrib><creatorcontrib>Wu, Jian-zhong</creatorcontrib><creatorcontrib>Hu, Sai-nan</creatorcontrib><creatorcontrib>Gao, Chang-ming</creatorcontrib><creatorcontrib>Shi, Mei-qi</creatorcontrib><creatorcontrib>Lu, Zhu-hong</creatorcontrib><creatorcontrib>Sun, Xin-chen</creatorcontrib><creatorcontrib>Zhou, Jin-Rong</creatorcontrib><creatorcontrib>Chen, Bao-an</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>Lung cancer (Amsterdam, Netherlands)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Feng, Ji-feng</au><au>Wu, Jian-zhong</au><au>Hu, Sai-nan</au><au>Gao, Chang-ming</au><au>Shi, Mei-qi</au><au>Lu, Zhu-hong</au><au>Sun, Xin-chen</au><au>Zhou, Jin-Rong</au><au>Chen, Bao-an</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Polymorphisms of the ribonucleotide reductase M1 gene and sensitivity to platin-based chemotherapy in non-small cell lung cancer</atitle><jtitle>Lung cancer (Amsterdam, Netherlands)</jtitle><addtitle>Lung Cancer</addtitle><date>2009-12-01</date><risdate>2009</risdate><volume>66</volume><issue>3</issue><spage>344</spage><epage>349</epage><pages>344-349</pages><issn>0169-5002</issn><eissn>1872-8332</eissn><coden>LUCAE5</coden><abstract>Abstract Ribonucleotide reductase catalyzes the rate limiting step of deoxyribonucleotide formation, a crucially important step in DNA synthesis and repair. The regulatory subunit M1 of ribonucleotide reductase (RRM1) is the necessary part of the RR function and controls substrate specificity and global on/off enzyme activity. Despite recent research progress, the role of RRM1 in lung cancer sensitivity to chemotherapeutics remains to be elucidated. This study was to investigate the relationship between polymorphisms of the RRM1 gene and sensitivity to platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Genomic DNA samples from 214 NSCLC patients treated with platinum-based chemotherapy were used to determine the RRM1 promoter allelotypes. The RR37CC-RR524TT was the most frequent allelotype (38.50%), followed by RR37AC-RR524CT (26.76%) and RR37CC-RR524CT (14.95%). The average response rate for chemotherapy was 44.4%. The response rates to the treatment regimens in the RR37CC-RR524TT, RR37AC-RR524CT and RR37CC-RR524CT allelotypes were 43.9%, 52.6%, and 51.6%, respectively. The response rates to therapy among patients with RRM1 (−)524 allelotypes were significantly different ( p = 0.046), whereas that among patients with RRM1 (−)37 allelotypes were not significant. Further analysis showed that the response rate in the patients with RR524CT allelotype (52.3%) was the highest, compared with that with RR37CC-RR524TT allelotype (43.9%, p = 0.28), or the Others (RR524CC and RR37AC-RR524TT, 30.2%, p = 0.02). Our results suggest that the RR524CT allelotype may be associated with an increased sensitivity to platinum-based chemotherapy in NSCLC. Further research on determining RR524CT as a clinical marker for predicting response to platinum-based therapy in NSCLC patients is warranted.</abstract><cop>Oxford</cop><pub>Elsevier Ireland Ltd</pub><pmid>19304340</pmid><doi>10.1016/j.lungcan.2009.02.015</doi><tpages>6</tpages></addata></record>
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subjects Adult
Aged
Biological and medical sciences
Biomarkers, Pharmacological - metabolism
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - pathology
Chemotherapy
Drug Resistance, Neoplasm - genetics
Female
Genetic polymorphism
Genetic Testing
Hematology, Oncology and Palliative Medicine
Humans
Lung Neoplasms - drug therapy
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Male
Medical sciences
Middle Aged
Neoplasm Staging
Non-small cell lung cancer
Platinum
Platinum Compounds - therapeutic use
Pneumology
Polymorphism, Genetic
Pulmonary/Respiratory
RRM1
Tumor Suppressor Proteins - genetics
Tumor Suppressor Proteins - metabolism
Tumors
Tumors of the respiratory system and mediastinum
title Polymorphisms of the ribonucleotide reductase M1 gene and sensitivity to platin-based chemotherapy in non-small cell lung cancer
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