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ABCB1 c.3435C>T polymorphism is associated with platinum toxicity: a preliminary study
Background Platinum-based doublets are the standard chemotherapy for lung cancer. The identification of markers associated with drug toxicity may improve the success of the treatment. Single nucleotide polymorphisms (SNPs) mapping into the genes involved in platinum transport or detoxification may e...
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Published in: | Cancer chemotherapy and pharmacology 2019-04, Vol.83 (4), p.803-808 |
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creator | De Troia, Beatrice Dalu, Davide Filipazzi, Virginio Isabella, Luigi Tosca, Nicoletta Ferrario, Sabrina Gambaro, Anna Rita Somma, Luisa Fasola, Cinzia Cheli, Stefania Clementi, Emilio De Francesco, Davide Falvella, Felicia Stefania Cattaneo, Maria Teresa |
description | Background
Platinum-based doublets are the standard chemotherapy for lung cancer. The identification of markers associated with drug toxicity may improve the success of the treatment. Single nucleotide polymorphisms (SNPs) mapping into the genes involved in platinum transport or detoxification may explain the occurrence of toxicities. In this study, we evaluated the role of three SNPs in predicting the onset of adverse events for lung cancer patients receiving cisplatin or carboplatin in adjuvant, neo-adjuvant and metastatic settings.
Methods
Eighty-two patients affected by non-small-cell and small-cell lung cancer treated with cisplatin- or carboplatin-based chemotherapy (stage II–IV) were enrolled. Before genetic analysis, patients signed a written informed consent. DNA was extracted from peripheral blood samples and genotypes were determined by real-time PCR. We selected and analyzed three SNPs:
ABCB1
c.3435C>T/rs1045642,
ABCC2
-24C>T/rs717620 and
GSTP1
c.313A>G/rs1695. Patient characteristics and genotypes were correlated with hematological, gastrointestinal and renal toxicity as recorded by Common Terminology Criteria for Adverse Event (CTCAE) v4.03. No neurological toxicity was observed in our patients.
Results
Variant alleles were present in 53% of patients for
ABCB1
c.3435C >T, 18.3% for
ABCC2
-24C> T, and 34.8% for
GSTP1
c.313A>G. Heterozygous CT at
ABCB1
c.3435 was associated to a lower risk of hematological toxicity compared to homozygous CC (OR = 0.20; 95% CI 0.05, 0.69;
p
= 0.01). Similar results were observed by genetic dominant model (CT + TT vs CC) and hematological toxicity (OR = 0.26; 95% CI 0.09, 0.79;
p
= 0.02). No other significant associations were found between toxicity and SNPs. Multivariate analysis confirmed an independent value for the
ABCB1
c.3435 C >T polymorphism.
Conclusions
The present study reveals that
ABCB1
c.3435C>T polymorphism influences platinum toxicity. The T allele seems to exert a protective effect on the development of toxicities. Further studies, such as epigenetic regulation ones, are needed to validate and shed more light on this association. |
doi_str_mv | 10.1007/s00280-019-03794-6 |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2185560118</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2185560118</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3346-f5b2c095aa2ec8dd2287ef4ed5b4f6444989e72af4546d674d6b4595188f9bcc3</originalsourceid><addsrcrecordid>eNp9kE1P3DAQhq2KqrvQ_oEeKktcuGQZ22PH4VAJVkCRkHqhXC3Hcbpe5at2Ith_T2ChSD30NId55p2Zh5CvDFYMID9NAFxDBqzIQOQFZuoDWTIUPAON4oAsQSBmMgdckMOUtgCATIhPZCEgLxQqXJL784v1BaNuJVDI9fc7OvTNru3jsAmppSFRm1Lvgh19RR_CuKFDY8fQTS0d-8fgwrg7o5YO0TehDZ2NO5rGqdp9Jh9r2yT_5bUekV9Xl3frH9ntz-ub9flt5oRAldWy5A4KaS33TlcV5zr3NfpKllgrRCx04XNua5SoKpVjpUqUhWRa10XpnDgiJ_vcIfZ_Jp9G04bkfNPYzvdTMpxpKRUwpmf0-B9020-xm697plArrUDOFN9TLvYpRV-bIYZ2_sswMM_Wzd66ma2bF-tGzUPfXqOnsvXV35E3zTMg9kCaW91vH993_yf2CebLi1A</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2184868605</pqid></control><display><type>article</type><title>ABCB1 c.3435C>T polymorphism is associated with platinum toxicity: a preliminary study</title><source>Springer Nature</source><creator>De Troia, Beatrice ; Dalu, Davide ; Filipazzi, Virginio ; Isabella, Luigi ; Tosca, Nicoletta ; Ferrario, Sabrina ; Gambaro, Anna Rita ; Somma, Luisa ; Fasola, Cinzia ; Cheli, Stefania ; Clementi, Emilio ; De Francesco, Davide ; Falvella, Felicia Stefania ; Cattaneo, Maria Teresa</creator><creatorcontrib>De Troia, Beatrice ; Dalu, Davide ; Filipazzi, Virginio ; Isabella, Luigi ; Tosca, Nicoletta ; Ferrario, Sabrina ; Gambaro, Anna Rita ; Somma, Luisa ; Fasola, Cinzia ; Cheli, Stefania ; Clementi, Emilio ; De Francesco, Davide ; Falvella, Felicia Stefania ; Cattaneo, Maria Teresa</creatorcontrib><description>Background
Platinum-based doublets are the standard chemotherapy for lung cancer. The identification of markers associated with drug toxicity may improve the success of the treatment. Single nucleotide polymorphisms (SNPs) mapping into the genes involved in platinum transport or detoxification may explain the occurrence of toxicities. In this study, we evaluated the role of three SNPs in predicting the onset of adverse events for lung cancer patients receiving cisplatin or carboplatin in adjuvant, neo-adjuvant and metastatic settings.
Methods
Eighty-two patients affected by non-small-cell and small-cell lung cancer treated with cisplatin- or carboplatin-based chemotherapy (stage II–IV) were enrolled. Before genetic analysis, patients signed a written informed consent. DNA was extracted from peripheral blood samples and genotypes were determined by real-time PCR. We selected and analyzed three SNPs:
ABCB1
c.3435C>T/rs1045642,
ABCC2
-24C>T/rs717620 and
GSTP1
c.313A>G/rs1695. Patient characteristics and genotypes were correlated with hematological, gastrointestinal and renal toxicity as recorded by Common Terminology Criteria for Adverse Event (CTCAE) v4.03. No neurological toxicity was observed in our patients.
Results
Variant alleles were present in 53% of patients for
ABCB1
c.3435C >T, 18.3% for
ABCC2
-24C> T, and 34.8% for
GSTP1
c.313A>G. Heterozygous CT at
ABCB1
c.3435 was associated to a lower risk of hematological toxicity compared to homozygous CC (OR = 0.20; 95% CI 0.05, 0.69;
p
= 0.01). Similar results were observed by genetic dominant model (CT + TT vs CC) and hematological toxicity (OR = 0.26; 95% CI 0.09, 0.79;
p
= 0.02). No other significant associations were found between toxicity and SNPs. Multivariate analysis confirmed an independent value for the
ABCB1
c.3435 C >T polymorphism.
Conclusions
The present study reveals that
ABCB1
c.3435C>T polymorphism influences platinum toxicity. The T allele seems to exert a protective effect on the development of toxicities. Further studies, such as epigenetic regulation ones, are needed to validate and shed more light on this association.</description><identifier>ISSN: 0344-5704</identifier><identifier>EISSN: 1432-0843</identifier><identifier>DOI: 10.1007/s00280-019-03794-6</identifier><identifier>PMID: 30796464</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Alleles ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; ATP Binding Cassette Transporter, Subfamily B - genetics ; Cancer ; Cancer Research ; Carboplatin ; Carboplatin - administration & dosage ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - pathology ; Chemotherapy ; Cisplatin ; Cisplatin - administration & dosage ; Deoxyribonucleic acid ; Detoxification ; DNA ; Female ; Gene mapping ; Gene polymorphism ; Genetic analysis ; Genotype ; Genotypes ; Glutathione transferase ; Hematology ; Humans ; Informed consent ; Lung cancer ; Lung Neoplasms - drug therapy ; Lung Neoplasms - pathology ; Male ; Mapping ; Medicine ; Medicine & Public Health ; Metastases ; Multivariate analysis ; Neoplasm Staging ; Oncology ; Patients ; Peripheral blood ; Pharmacology/Toxicology ; Platinum ; Polymorphism ; Polymorphism, Single Nucleotide ; Short Communication ; Single-nucleotide polymorphism ; Small Cell Lung Carcinoma - drug therapy ; Small Cell Lung Carcinoma - pathology ; Terminology ; Toxicity</subject><ispartof>Cancer chemotherapy and pharmacology, 2019-04, Vol.83 (4), p.803-808</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2019</rights><rights>Cancer Chemotherapy and Pharmacology is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3346-f5b2c095aa2ec8dd2287ef4ed5b4f6444989e72af4546d674d6b4595188f9bcc3</citedby><cites>FETCH-LOGICAL-c3346-f5b2c095aa2ec8dd2287ef4ed5b4f6444989e72af4546d674d6b4595188f9bcc3</cites><orcidid>0000-0003-2721-6082</orcidid></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/30796464$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>De Troia, Beatrice</creatorcontrib><creatorcontrib>Dalu, Davide</creatorcontrib><creatorcontrib>Filipazzi, Virginio</creatorcontrib><creatorcontrib>Isabella, Luigi</creatorcontrib><creatorcontrib>Tosca, Nicoletta</creatorcontrib><creatorcontrib>Ferrario, Sabrina</creatorcontrib><creatorcontrib>Gambaro, Anna Rita</creatorcontrib><creatorcontrib>Somma, Luisa</creatorcontrib><creatorcontrib>Fasola, Cinzia</creatorcontrib><creatorcontrib>Cheli, Stefania</creatorcontrib><creatorcontrib>Clementi, Emilio</creatorcontrib><creatorcontrib>De Francesco, Davide</creatorcontrib><creatorcontrib>Falvella, Felicia Stefania</creatorcontrib><creatorcontrib>Cattaneo, Maria Teresa</creatorcontrib><title>ABCB1 c.3435C>T polymorphism is associated with platinum toxicity: a preliminary study</title><title>Cancer chemotherapy and pharmacology</title><addtitle>Cancer Chemother Pharmacol</addtitle><addtitle>Cancer Chemother Pharmacol</addtitle><description>Background
Platinum-based doublets are the standard chemotherapy for lung cancer. The identification of markers associated with drug toxicity may improve the success of the treatment. Single nucleotide polymorphisms (SNPs) mapping into the genes involved in platinum transport or detoxification may explain the occurrence of toxicities. In this study, we evaluated the role of three SNPs in predicting the onset of adverse events for lung cancer patients receiving cisplatin or carboplatin in adjuvant, neo-adjuvant and metastatic settings.
Methods
Eighty-two patients affected by non-small-cell and small-cell lung cancer treated with cisplatin- or carboplatin-based chemotherapy (stage II–IV) were enrolled. Before genetic analysis, patients signed a written informed consent. DNA was extracted from peripheral blood samples and genotypes were determined by real-time PCR. We selected and analyzed three SNPs:
ABCB1
c.3435C>T/rs1045642,
ABCC2
-24C>T/rs717620 and
GSTP1
c.313A>G/rs1695. Patient characteristics and genotypes were correlated with hematological, gastrointestinal and renal toxicity as recorded by Common Terminology Criteria for Adverse Event (CTCAE) v4.03. No neurological toxicity was observed in our patients.
Results
Variant alleles were present in 53% of patients for
ABCB1
c.3435C >T, 18.3% for
ABCC2
-24C> T, and 34.8% for
GSTP1
c.313A>G. Heterozygous CT at
ABCB1
c.3435 was associated to a lower risk of hematological toxicity compared to homozygous CC (OR = 0.20; 95% CI 0.05, 0.69;
p
= 0.01). Similar results were observed by genetic dominant model (CT + TT vs CC) and hematological toxicity (OR = 0.26; 95% CI 0.09, 0.79;
p
= 0.02). No other significant associations were found between toxicity and SNPs. Multivariate analysis confirmed an independent value for the
ABCB1
c.3435 C >T polymorphism.
Conclusions
The present study reveals that
ABCB1
c.3435C>T polymorphism influences platinum toxicity. The T allele seems to exert a protective effect on the development of toxicities. Further studies, such as epigenetic regulation ones, are needed to validate and shed more light on this association.</description><subject>Alleles</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>ATP Binding Cassette Transporter, Subfamily B - genetics</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Carboplatin</subject><subject>Carboplatin - administration & dosage</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Chemotherapy</subject><subject>Cisplatin</subject><subject>Cisplatin - administration & dosage</subject><subject>Deoxyribonucleic acid</subject><subject>Detoxification</subject><subject>DNA</subject><subject>Female</subject><subject>Gene mapping</subject><subject>Gene polymorphism</subject><subject>Genetic analysis</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>Glutathione transferase</subject><subject>Hematology</subject><subject>Humans</subject><subject>Informed consent</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Mapping</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastases</subject><subject>Multivariate analysis</subject><subject>Neoplasm Staging</subject><subject>Oncology</subject><subject>Patients</subject><subject>Peripheral blood</subject><subject>Pharmacology/Toxicology</subject><subject>Platinum</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Short Communication</subject><subject>Single-nucleotide polymorphism</subject><subject>Small Cell Lung Carcinoma - drug therapy</subject><subject>Small Cell Lung Carcinoma - pathology</subject><subject>Terminology</subject><subject>Toxicity</subject><issn>0344-5704</issn><issn>1432-0843</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kE1P3DAQhq2KqrvQ_oEeKktcuGQZ22PH4VAJVkCRkHqhXC3Hcbpe5at2Ith_T2ChSD30NId55p2Zh5CvDFYMID9NAFxDBqzIQOQFZuoDWTIUPAON4oAsQSBmMgdckMOUtgCATIhPZCEgLxQqXJL784v1BaNuJVDI9fc7OvTNru3jsAmppSFRm1Lvgh19RR_CuKFDY8fQTS0d-8fgwrg7o5YO0TehDZ2NO5rGqdp9Jh9r2yT_5bUekV9Xl3frH9ntz-ub9flt5oRAldWy5A4KaS33TlcV5zr3NfpKllgrRCx04XNua5SoKpVjpUqUhWRa10XpnDgiJ_vcIfZ_Jp9G04bkfNPYzvdTMpxpKRUwpmf0-B9020-xm697plArrUDOFN9TLvYpRV-bIYZ2_sswMM_Wzd66ma2bF-tGzUPfXqOnsvXV35E3zTMg9kCaW91vH993_yf2CebLi1A</recordid><startdate>201904</startdate><enddate>201904</enddate><creator>De Troia, Beatrice</creator><creator>Dalu, Davide</creator><creator>Filipazzi, Virginio</creator><creator>Isabella, Luigi</creator><creator>Tosca, Nicoletta</creator><creator>Ferrario, Sabrina</creator><creator>Gambaro, Anna Rita</creator><creator>Somma, Luisa</creator><creator>Fasola, Cinzia</creator><creator>Cheli, Stefania</creator><creator>Clementi, Emilio</creator><creator>De Francesco, Davide</creator><creator>Falvella, Felicia Stefania</creator><creator>Cattaneo, Maria Teresa</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><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>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2721-6082</orcidid></search><sort><creationdate>201904</creationdate><title>ABCB1 c.3435C>T polymorphism is associated with platinum toxicity: a preliminary study</title><author>De Troia, Beatrice ; Dalu, Davide ; Filipazzi, Virginio ; Isabella, Luigi ; Tosca, Nicoletta ; Ferrario, Sabrina ; Gambaro, Anna Rita ; Somma, Luisa ; Fasola, Cinzia ; Cheli, Stefania ; Clementi, Emilio ; De Francesco, Davide ; Falvella, Felicia Stefania ; Cattaneo, Maria Teresa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3346-f5b2c095aa2ec8dd2287ef4ed5b4f6444989e72af4546d674d6b4595188f9bcc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Alleles</topic><topic>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols - adverse effects</topic><topic>ATP Binding Cassette Transporter, Subfamily B - genetics</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Carboplatin</topic><topic>Carboplatin - administration & dosage</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Chemotherapy</topic><topic>Cisplatin</topic><topic>Cisplatin - administration & dosage</topic><topic>Deoxyribonucleic acid</topic><topic>Detoxification</topic><topic>DNA</topic><topic>Female</topic><topic>Gene mapping</topic><topic>Gene polymorphism</topic><topic>Genetic analysis</topic><topic>Genotype</topic><topic>Genotypes</topic><topic>Glutathione transferase</topic><topic>Hematology</topic><topic>Humans</topic><topic>Informed consent</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Mapping</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastases</topic><topic>Multivariate analysis</topic><topic>Neoplasm Staging</topic><topic>Oncology</topic><topic>Patients</topic><topic>Peripheral blood</topic><topic>Pharmacology/Toxicology</topic><topic>Platinum</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Short Communication</topic><topic>Single-nucleotide polymorphism</topic><topic>Small Cell Lung Carcinoma - drug therapy</topic><topic>Small Cell Lung Carcinoma - pathology</topic><topic>Terminology</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>De Troia, Beatrice</creatorcontrib><creatorcontrib>Dalu, Davide</creatorcontrib><creatorcontrib>Filipazzi, Virginio</creatorcontrib><creatorcontrib>Isabella, Luigi</creatorcontrib><creatorcontrib>Tosca, Nicoletta</creatorcontrib><creatorcontrib>Ferrario, Sabrina</creatorcontrib><creatorcontrib>Gambaro, Anna Rita</creatorcontrib><creatorcontrib>Somma, Luisa</creatorcontrib><creatorcontrib>Fasola, Cinzia</creatorcontrib><creatorcontrib>Cheli, Stefania</creatorcontrib><creatorcontrib>Clementi, Emilio</creatorcontrib><creatorcontrib>De Francesco, Davide</creatorcontrib><creatorcontrib>Falvella, Felicia Stefania</creatorcontrib><creatorcontrib>Cattaneo, Maria Teresa</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Proquest Health and Medical Complete</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer chemotherapy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>De Troia, Beatrice</au><au>Dalu, Davide</au><au>Filipazzi, Virginio</au><au>Isabella, Luigi</au><au>Tosca, Nicoletta</au><au>Ferrario, Sabrina</au><au>Gambaro, Anna Rita</au><au>Somma, Luisa</au><au>Fasola, Cinzia</au><au>Cheli, Stefania</au><au>Clementi, Emilio</au><au>De Francesco, Davide</au><au>Falvella, Felicia Stefania</au><au>Cattaneo, Maria Teresa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ABCB1 c.3435C>T polymorphism is associated with platinum toxicity: a preliminary study</atitle><jtitle>Cancer chemotherapy and pharmacology</jtitle><stitle>Cancer Chemother Pharmacol</stitle><addtitle>Cancer Chemother Pharmacol</addtitle><date>2019-04</date><risdate>2019</risdate><volume>83</volume><issue>4</issue><spage>803</spage><epage>808</epage><pages>803-808</pages><issn>0344-5704</issn><eissn>1432-0843</eissn><abstract>Background
Platinum-based doublets are the standard chemotherapy for lung cancer. The identification of markers associated with drug toxicity may improve the success of the treatment. Single nucleotide polymorphisms (SNPs) mapping into the genes involved in platinum transport or detoxification may explain the occurrence of toxicities. In this study, we evaluated the role of three SNPs in predicting the onset of adverse events for lung cancer patients receiving cisplatin or carboplatin in adjuvant, neo-adjuvant and metastatic settings.
Methods
Eighty-two patients affected by non-small-cell and small-cell lung cancer treated with cisplatin- or carboplatin-based chemotherapy (stage II–IV) were enrolled. Before genetic analysis, patients signed a written informed consent. DNA was extracted from peripheral blood samples and genotypes were determined by real-time PCR. We selected and analyzed three SNPs:
ABCB1
c.3435C>T/rs1045642,
ABCC2
-24C>T/rs717620 and
GSTP1
c.313A>G/rs1695. Patient characteristics and genotypes were correlated with hematological, gastrointestinal and renal toxicity as recorded by Common Terminology Criteria for Adverse Event (CTCAE) v4.03. No neurological toxicity was observed in our patients.
Results
Variant alleles were present in 53% of patients for
ABCB1
c.3435C >T, 18.3% for
ABCC2
-24C> T, and 34.8% for
GSTP1
c.313A>G. Heterozygous CT at
ABCB1
c.3435 was associated to a lower risk of hematological toxicity compared to homozygous CC (OR = 0.20; 95% CI 0.05, 0.69;
p
= 0.01). Similar results were observed by genetic dominant model (CT + TT vs CC) and hematological toxicity (OR = 0.26; 95% CI 0.09, 0.79;
p
= 0.02). No other significant associations were found between toxicity and SNPs. Multivariate analysis confirmed an independent value for the
ABCB1
c.3435 C >T polymorphism.
Conclusions
The present study reveals that
ABCB1
c.3435C>T polymorphism influences platinum toxicity. The T allele seems to exert a protective effect on the development of toxicities. Further studies, such as epigenetic regulation ones, are needed to validate and shed more light on this association.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>30796464</pmid><doi>10.1007/s00280-019-03794-6</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0003-2721-6082</orcidid><oa>free_for_read</oa></addata></record> |
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ispartof | Cancer chemotherapy and pharmacology, 2019-04, Vol.83 (4), p.803-808 |
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language | eng |
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source | Springer Nature |
subjects | Alleles Antineoplastic Combined Chemotherapy Protocols - administration & dosage Antineoplastic Combined Chemotherapy Protocols - adverse effects ATP Binding Cassette Transporter, Subfamily B - genetics Cancer Cancer Research Carboplatin Carboplatin - administration & dosage Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - pathology Chemotherapy Cisplatin Cisplatin - administration & dosage Deoxyribonucleic acid Detoxification DNA Female Gene mapping Gene polymorphism Genetic analysis Genotype Genotypes Glutathione transferase Hematology Humans Informed consent Lung cancer Lung Neoplasms - drug therapy Lung Neoplasms - pathology Male Mapping Medicine Medicine & Public Health Metastases Multivariate analysis Neoplasm Staging Oncology Patients Peripheral blood Pharmacology/Toxicology Platinum Polymorphism Polymorphism, Single Nucleotide Short Communication Single-nucleotide polymorphism Small Cell Lung Carcinoma - drug therapy Small Cell Lung Carcinoma - pathology Terminology Toxicity |
title | ABCB1 c.3435C>T polymorphism is associated with platinum toxicity: a preliminary study |
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