Clinical Significance of ABCG2 Haplotype-tagging Single Nucleotide Polymorphisms in Patients With Unresectable Non-Small Cell Lung Cancer Treated With First-line Platinum-based Chemotherapy
The ATP-binding cassette (ABC) ABCG2, involved in multidrug resistance (MDR) in cancer cells, plays an integral role in drug resistance. Single nucleotide polymorphisms (SNPs) have been identified in many MDR-associated ABC genes that seem to influence drug sensitivity/resistance through various mec...
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| Veröffentlicht in: | American journal of clinical oncology 2015-06, Vol.38 (3), p.294-299 |
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| creator | Kim, Seok-Hyun Kim, Moon Jin Cho, Yu Ji Jeong, Yi Yeong Kim, Ho-Cheol Lee, Jong Duk Hwang, Young Sil Kim, In-Suk Lee, Suee Oh, Sung Yong Ling, Hui Lee, Gyeong-Won |
| description | The ATP-binding cassette (ABC) ABCG2, involved in multidrug resistance (MDR) in cancer cells, plays an integral role in drug resistance. Single nucleotide polymorphisms (SNPs) have been identified in many MDR-associated ABC genes that seem to influence drug sensitivity/resistance through various mechanisms. Therefore, we investigated whether ABCG2 haplotype-tagging SNPs (htSNPs) were associated with clinical outcomes in patients with unresectable non-small cell lung cancer (NSCLC) treated with front-line platinum-based chemotherapy.
We genotyped 4 ABCG2 htSNPs for 129 unresectable NSCLC cases treated with first-line platinum-based chemotherapy. Clinical characteristics, treatment outcomes, and predictive value of the htSNPs in patient response, survival, and adverse events related to platinum-based chemotherapy were analyzed according to each ABCG2 htSNP using the χ test, Kaplan-Meier method, and Cox proportional hazard model.
The rs2725264 was significantly related to overall survival (OS) (P=0.018, log-rank test). The median survival duration (in months) for patients with the rs2725264 T/T, T/C, and C/C genotypes was 35.75 (95% confidence interval [CI], 24.25-47.25), 34.25 (hazard ratio [HR] 1.27 [0.68 to 2.35]; 95% CI, 27.16-41.34), and 14.89 (HR 3.22 [1.26 to 8.24], 95% CI, 13.86-15.92), respectively. The rs2725264 was identified as an independent factor by Cox proportional hazard model analysis (P=0.028). In the taxane-based groups, OS was associated with rs2725264 (P=0.041), whereas in the gemcitabine-based groups, OS was associated with rs4148149 (P=0.014).
Our data suggest ABCG2 htSNPs rs2725264 (overall group and taxane-platinum combination group) and rs4148149 (gemcitabine-platinum combination group) were associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy. Thus, the ABCG2 htSNP rs2725264 may be independently associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy. |
| doi_str_mv | 10.1097/COC.0b013e318297f333 |
| format | Article |
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We genotyped 4 ABCG2 htSNPs for 129 unresectable NSCLC cases treated with first-line platinum-based chemotherapy. Clinical characteristics, treatment outcomes, and predictive value of the htSNPs in patient response, survival, and adverse events related to platinum-based chemotherapy were analyzed according to each ABCG2 htSNP using the χ test, Kaplan-Meier method, and Cox proportional hazard model.
The rs2725264 was significantly related to overall survival (OS) (P=0.018, log-rank test). The median survival duration (in months) for patients with the rs2725264 T/T, T/C, and C/C genotypes was 35.75 (95% confidence interval [CI], 24.25-47.25), 34.25 (hazard ratio [HR] 1.27 [0.68 to 2.35]; 95% CI, 27.16-41.34), and 14.89 (HR 3.22 [1.26 to 8.24], 95% CI, 13.86-15.92), respectively. The rs2725264 was identified as an independent factor by Cox proportional hazard model analysis (P=0.028). In the taxane-based groups, OS was associated with rs2725264 (P=0.041), whereas in the gemcitabine-based groups, OS was associated with rs4148149 (P=0.014).
Our data suggest ABCG2 htSNPs rs2725264 (overall group and taxane-platinum combination group) and rs4148149 (gemcitabine-platinum combination group) were associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy. Thus, the ABCG2 htSNP rs2725264 may be independently associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy.</description><identifier>ISSN: 0277-3732</identifier><identifier>EISSN: 1537-453X</identifier><identifier>DOI: 10.1097/COC.0b013e318297f333</identifier><identifier>PMID: 23689644</identifier><language>eng</language><publisher>United States</publisher><subject><![CDATA[Aged ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters - genetics ; Bridged-Ring Compounds - administration & dosage ; Carboplatin - administration & dosage ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - pathology ; Carcinoma, Non-Small-Cell Lung - therapy ; Chemoradiotherapy ; Cisplatin - administration & dosage ; Deoxycytidine - administration & dosage ; Deoxycytidine - analogs & derivatives ; Disease-Free Survival ; Female ; Haplotypes ; Humans ; Lung Neoplasms - genetics ; Lung Neoplasms - pathology ; Lung Neoplasms - therapy ; Male ; Middle Aged ; Neoplasm Proteins - genetics ; Paclitaxel - administration & dosage ; Polymorphism, Single Nucleotide ; Predictive Value of Tests ; Survival Rate ; Taxoids - administration & dosage ; Treatment Outcome]]></subject><ispartof>American journal of clinical oncology, 2015-06, Vol.38 (3), p.294-299</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c377t-116113697e9da5c2f0bb90caf98fbedcf7889ee88b5a3b373efd6944186dd7773</citedby><cites>FETCH-LOGICAL-c377t-116113697e9da5c2f0bb90caf98fbedcf7889ee88b5a3b373efd6944186dd7773</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23689644$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Seok-Hyun</creatorcontrib><creatorcontrib>Kim, Moon Jin</creatorcontrib><creatorcontrib>Cho, Yu Ji</creatorcontrib><creatorcontrib>Jeong, Yi Yeong</creatorcontrib><creatorcontrib>Kim, Ho-Cheol</creatorcontrib><creatorcontrib>Lee, Jong Duk</creatorcontrib><creatorcontrib>Hwang, Young Sil</creatorcontrib><creatorcontrib>Kim, In-Suk</creatorcontrib><creatorcontrib>Lee, Suee</creatorcontrib><creatorcontrib>Oh, Sung Yong</creatorcontrib><creatorcontrib>Ling, Hui</creatorcontrib><creatorcontrib>Lee, Gyeong-Won</creatorcontrib><title>Clinical Significance of ABCG2 Haplotype-tagging Single Nucleotide Polymorphisms in Patients With Unresectable Non-Small Cell Lung Cancer Treated With First-line Platinum-based Chemotherapy</title><title>American journal of clinical oncology</title><addtitle>Am J Clin Oncol</addtitle><description>The ATP-binding cassette (ABC) ABCG2, involved in multidrug resistance (MDR) in cancer cells, plays an integral role in drug resistance. Single nucleotide polymorphisms (SNPs) have been identified in many MDR-associated ABC genes that seem to influence drug sensitivity/resistance through various mechanisms. Therefore, we investigated whether ABCG2 haplotype-tagging SNPs (htSNPs) were associated with clinical outcomes in patients with unresectable non-small cell lung cancer (NSCLC) treated with front-line platinum-based chemotherapy.
We genotyped 4 ABCG2 htSNPs for 129 unresectable NSCLC cases treated with first-line platinum-based chemotherapy. Clinical characteristics, treatment outcomes, and predictive value of the htSNPs in patient response, survival, and adverse events related to platinum-based chemotherapy were analyzed according to each ABCG2 htSNP using the χ test, Kaplan-Meier method, and Cox proportional hazard model.
The rs2725264 was significantly related to overall survival (OS) (P=0.018, log-rank test). The median survival duration (in months) for patients with the rs2725264 T/T, T/C, and C/C genotypes was 35.75 (95% confidence interval [CI], 24.25-47.25), 34.25 (hazard ratio [HR] 1.27 [0.68 to 2.35]; 95% CI, 27.16-41.34), and 14.89 (HR 3.22 [1.26 to 8.24], 95% CI, 13.86-15.92), respectively. The rs2725264 was identified as an independent factor by Cox proportional hazard model analysis (P=0.028). In the taxane-based groups, OS was associated with rs2725264 (P=0.041), whereas in the gemcitabine-based groups, OS was associated with rs4148149 (P=0.014).
Our data suggest ABCG2 htSNPs rs2725264 (overall group and taxane-platinum combination group) and rs4148149 (gemcitabine-platinum combination group) were associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy. Thus, the ABCG2 htSNP rs2725264 may be independently associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy.</description><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>ATP Binding Cassette Transporter, Sub-Family G, Member 2</subject><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>Bridged-Ring Compounds - administration & dosage</subject><subject>Carboplatin - administration & dosage</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Carcinoma, Non-Small-Cell Lung - therapy</subject><subject>Chemoradiotherapy</subject><subject>Cisplatin - administration & dosage</subject><subject>Deoxycytidine - administration & dosage</subject><subject>Deoxycytidine - analogs & derivatives</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - pathology</subject><subject>Lung Neoplasms - therapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Proteins - genetics</subject><subject>Paclitaxel - administration & dosage</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Predictive Value of Tests</subject><subject>Survival Rate</subject><subject>Taxoids - administration & dosage</subject><subject>Treatment Outcome</subject><issn>0277-3732</issn><issn>1537-453X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUU1v1DAQtRCILoV_gJCPXFLsOLGdY4noh7SildoKbpHjjHeNHDvYzmF_HP8Nr7b0wGVmpHnvzcdD6CMlF5R04kt_11-QkVAGjMq6E4Yx9gptaMtE1bTs52u0IbUQFROsPkPvUvpFCGk5EW_RWc247HjTbNCf3llvtXL4we68NaX0GnAw-PJrf13jG7W4kA8LVFntdtbvCs7vHODvq3YQsp0A3wd3mENc9jbNCVuP71W24HPCP2ze4ycfIYHOajzSgq8eZuUc7qGE7VoU--PIiB8jqAzTiXRlY8pV2a3IuyLn17kaVSrtfg9zyHuIajm8R2-Mcgk-POdz9HT17bG_qbZ317f95bbSTIhcUcopZbwT0E2q1bUh49gRrUwnzQiTNkLKDkDKsVVsLA8DM_Guaajk0ySEYOfo80l3ieH3CikPs026HKA8hDUNlEtGhOS8K9DmBNUxpBTBDEu0s4qHgZLhaNxQjBv-N67QPj1PWMcZphfSP6fYX89RmKk</recordid><startdate>20150601</startdate><enddate>20150601</enddate><creator>Kim, Seok-Hyun</creator><creator>Kim, Moon Jin</creator><creator>Cho, Yu Ji</creator><creator>Jeong, Yi Yeong</creator><creator>Kim, Ho-Cheol</creator><creator>Lee, Jong Duk</creator><creator>Hwang, Young Sil</creator><creator>Kim, In-Suk</creator><creator>Lee, Suee</creator><creator>Oh, Sung Yong</creator><creator>Ling, Hui</creator><creator>Lee, Gyeong-Won</creator><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>20150601</creationdate><title>Clinical Significance of ABCG2 Haplotype-tagging Single Nucleotide Polymorphisms in Patients With Unresectable Non-Small Cell Lung Cancer Treated With First-line Platinum-based Chemotherapy</title><author>Kim, Seok-Hyun ; Kim, Moon Jin ; Cho, Yu Ji ; Jeong, Yi Yeong ; Kim, Ho-Cheol ; Lee, Jong Duk ; Hwang, Young Sil ; Kim, In-Suk ; Lee, Suee ; Oh, Sung Yong ; Ling, Hui ; Lee, Gyeong-Won</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c377t-116113697e9da5c2f0bb90caf98fbedcf7889ee88b5a3b373efd6944186dd7773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aged</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>ATP Binding Cassette Transporter, Sub-Family G, Member 2</topic><topic>ATP-Binding Cassette Transporters - genetics</topic><topic>Bridged-Ring Compounds - administration & dosage</topic><topic>Carboplatin - administration & dosage</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Carcinoma, Non-Small-Cell Lung - therapy</topic><topic>Chemoradiotherapy</topic><topic>Cisplatin - administration & dosage</topic><topic>Deoxycytidine - administration & dosage</topic><topic>Deoxycytidine - analogs & derivatives</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Haplotypes</topic><topic>Humans</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - pathology</topic><topic>Lung Neoplasms - therapy</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Proteins - genetics</topic><topic>Paclitaxel - administration & dosage</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Predictive Value of Tests</topic><topic>Survival Rate</topic><topic>Taxoids - administration & dosage</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Seok-Hyun</creatorcontrib><creatorcontrib>Kim, Moon Jin</creatorcontrib><creatorcontrib>Cho, Yu Ji</creatorcontrib><creatorcontrib>Jeong, Yi Yeong</creatorcontrib><creatorcontrib>Kim, Ho-Cheol</creatorcontrib><creatorcontrib>Lee, Jong Duk</creatorcontrib><creatorcontrib>Hwang, Young Sil</creatorcontrib><creatorcontrib>Kim, In-Suk</creatorcontrib><creatorcontrib>Lee, Suee</creatorcontrib><creatorcontrib>Oh, Sung Yong</creatorcontrib><creatorcontrib>Ling, Hui</creatorcontrib><creatorcontrib>Lee, Gyeong-Won</creatorcontrib><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>American journal of clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Seok-Hyun</au><au>Kim, Moon Jin</au><au>Cho, Yu Ji</au><au>Jeong, Yi Yeong</au><au>Kim, Ho-Cheol</au><au>Lee, Jong Duk</au><au>Hwang, Young Sil</au><au>Kim, In-Suk</au><au>Lee, Suee</au><au>Oh, Sung Yong</au><au>Ling, Hui</au><au>Lee, Gyeong-Won</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical Significance of ABCG2 Haplotype-tagging Single Nucleotide Polymorphisms in Patients With Unresectable Non-Small Cell Lung Cancer Treated With First-line Platinum-based Chemotherapy</atitle><jtitle>American journal of clinical oncology</jtitle><addtitle>Am J Clin Oncol</addtitle><date>2015-06-01</date><risdate>2015</risdate><volume>38</volume><issue>3</issue><spage>294</spage><epage>299</epage><pages>294-299</pages><issn>0277-3732</issn><eissn>1537-453X</eissn><abstract>The ATP-binding cassette (ABC) ABCG2, involved in multidrug resistance (MDR) in cancer cells, plays an integral role in drug resistance. Single nucleotide polymorphisms (SNPs) have been identified in many MDR-associated ABC genes that seem to influence drug sensitivity/resistance through various mechanisms. Therefore, we investigated whether ABCG2 haplotype-tagging SNPs (htSNPs) were associated with clinical outcomes in patients with unresectable non-small cell lung cancer (NSCLC) treated with front-line platinum-based chemotherapy.
We genotyped 4 ABCG2 htSNPs for 129 unresectable NSCLC cases treated with first-line platinum-based chemotherapy. Clinical characteristics, treatment outcomes, and predictive value of the htSNPs in patient response, survival, and adverse events related to platinum-based chemotherapy were analyzed according to each ABCG2 htSNP using the χ test, Kaplan-Meier method, and Cox proportional hazard model.
The rs2725264 was significantly related to overall survival (OS) (P=0.018, log-rank test). The median survival duration (in months) for patients with the rs2725264 T/T, T/C, and C/C genotypes was 35.75 (95% confidence interval [CI], 24.25-47.25), 34.25 (hazard ratio [HR] 1.27 [0.68 to 2.35]; 95% CI, 27.16-41.34), and 14.89 (HR 3.22 [1.26 to 8.24], 95% CI, 13.86-15.92), respectively. The rs2725264 was identified as an independent factor by Cox proportional hazard model analysis (P=0.028). In the taxane-based groups, OS was associated with rs2725264 (P=0.041), whereas in the gemcitabine-based groups, OS was associated with rs4148149 (P=0.014).
Our data suggest ABCG2 htSNPs rs2725264 (overall group and taxane-platinum combination group) and rs4148149 (gemcitabine-platinum combination group) were associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy. Thus, the ABCG2 htSNP rs2725264 may be independently associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy.</abstract><cop>United States</cop><pmid>23689644</pmid><doi>10.1097/COC.0b013e318297f333</doi><tpages>6</tpages></addata></record> |
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| subjects | Aged Antineoplastic Combined Chemotherapy Protocols - therapeutic use ATP Binding Cassette Transporter, Sub-Family G, Member 2 ATP-Binding Cassette Transporters - genetics Bridged-Ring Compounds - administration & dosage Carboplatin - administration & dosage Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - pathology Carcinoma, Non-Small-Cell Lung - therapy Chemoradiotherapy Cisplatin - administration & dosage Deoxycytidine - administration & dosage Deoxycytidine - analogs & derivatives Disease-Free Survival Female Haplotypes Humans Lung Neoplasms - genetics Lung Neoplasms - pathology Lung Neoplasms - therapy Male Middle Aged Neoplasm Proteins - genetics Paclitaxel - administration & dosage Polymorphism, Single Nucleotide Predictive Value of Tests Survival Rate Taxoids - administration & dosage Treatment Outcome |
| title | Clinical Significance of ABCG2 Haplotype-tagging Single Nucleotide Polymorphisms in Patients With Unresectable Non-Small Cell Lung Cancer Treated With First-line Platinum-based Chemotherapy |
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