Pharmacogenetics of pemetrexed combination therapy in lung cancer: pathway analysis reveals novel toxicity associations
Identification of polymorphisms that influence pemetrexed tolerability could lead to individualised treatment regimens and improve quality of life. Twenty-eight polymorphisms within eleven candidate genes were genotyped using the Illumina Human Exome v1.1 BeadChip and tested for their association wi...
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| Veröffentlicht in: | The pharmacogenomics journal 2014-10, Vol.14 (5), p.411-417 |
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| creator | Corrigan, A Walker, J L Wickramasinghe, S Hernandez, M A Newhouse, S J Folarin, A A Lewis, C M Sanderson, J D Spicer, J Marinaki, A M |
| description | Identification of polymorphisms that influence pemetrexed tolerability could lead to individualised treatment regimens and improve quality of life. Twenty-eight polymorphisms within eleven candidate genes were genotyped using the Illumina Human Exome v1.1 BeadChip and tested for their association with the clinical outcomes of non-small cell lung cancer and mesothelioma patients receiving pemetrexed/platinum doublet chemotherapy (
n
=136).
GGH
rs11545078 was associated with a reduced incidence of grade ⩾3 toxicity within the first four cycles of therapy (odds ratio (OR) 0.25,
P
=0.018), as well as reduced grade ⩾3 haematological toxicity (OR 0.13,
P
=0.048).
DHFR
rs1650697 conferred an increased risk of grade ⩾3 toxicity (OR 2.14,
P
=0.034). Furthermore,
FOLR3
rs61734430 was associated with an increased likelihood of disease progression at mid-treatment radiological evaluation (OR 4.05,
P
=0.023). Polymorphisms within
SLC19A1
(rs3788189, rs1051298 and rs914232) were associated with overall survival. This study confirms previous pharmacogenetic associations and identifies novel markers of pemetrexed toxicity. |
| doi_str_mv | 10.1038/tpj.2014.13 |
| format | Article |
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n
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GGH
rs11545078 was associated with a reduced incidence of grade ⩾3 toxicity within the first four cycles of therapy (odds ratio (OR) 0.25,
P
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P
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DHFR
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P
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FOLR3
rs61734430 was associated with an increased likelihood of disease progression at mid-treatment radiological evaluation (OR 4.05,
P
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SLC19A1
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n
=136).
GGH
rs11545078 was associated with a reduced incidence of grade ⩾3 toxicity within the first four cycles of therapy (odds ratio (OR) 0.25,
P
=0.018), as well as reduced grade ⩾3 haematological toxicity (OR 0.13,
P
=0.048).
DHFR
rs1650697 conferred an increased risk of grade ⩾3 toxicity (OR 2.14,
P
=0.034). Furthermore,
FOLR3
rs61734430 was associated with an increased likelihood of disease progression at mid-treatment radiological evaluation (OR 4.05,
P
=0.023). Polymorphisms within
SLC19A1
(rs3788189, rs1051298 and rs914232) were associated with overall survival. This study confirms previous pharmacogenetic associations and identifies novel markers of pemetrexed toxicity.</description><subject>631/154/436/434</subject><subject>631/154/570</subject><subject>692/699/67/1059/99</subject><subject>692/699/67/1612/1350</subject><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>Antineoplastic Combined Chemotherapy Protocols - pharmacology</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Carboplatin - adverse effects</subject><subject>Carboplatin - therapeutic use</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Chemotherapy</subject><subject>Cisplatin - adverse effects</subject><subject>Cisplatin - therapeutic use</subject><subject>Complications and side effects</subject><subject>Dihydrofolate reductase</subject><subject>Disease Progression</subject><subject>Drug metabolism</subject><subject>Drug therapy</subject><subject>Gene Expression</subject><subject>Genetic aspects</subject><subject>Genetic polymorphisms</subject><subject>Glutamates - adverse effects</subject><subject>Glutamates - pharmacology</subject><subject>Glutamates - therapeutic use</subject><subject>Guanine - adverse effects</subject><subject>Guanine - analogs & derivatives</subject><subject>Guanine - pharmacology</subject><subject>Guanine - therapeutic use</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - genetics</subject><subject>Mesothelioma</subject><subject>Mesothelioma - drug therapy</subject><subject>Mesothelioma - genetics</subject><subject>Non-small cell lung carcinoma</subject><subject>Oncology</subject><subject>original-article</subject><subject>Pemetrexed</subject><subject>Pharmacogenetics</subject><subject>Pharmacotherapy</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Properties</subject><subject>Psychopharmacology</subject><subject>Quality of life</subject><subject>Retrospective Studies</subject><subject>Small cell lung carcinoma</subject><subject>Survival 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adverse effects</topic><topic>Carboplatin - therapeutic use</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Chemotherapy</topic><topic>Cisplatin - adverse effects</topic><topic>Cisplatin - therapeutic use</topic><topic>Complications and side effects</topic><topic>Dihydrofolate reductase</topic><topic>Disease Progression</topic><topic>Drug metabolism</topic><topic>Drug therapy</topic><topic>Gene Expression</topic><topic>Genetic aspects</topic><topic>Genetic polymorphisms</topic><topic>Glutamates - adverse effects</topic><topic>Glutamates - pharmacology</topic><topic>Glutamates - therapeutic use</topic><topic>Guanine - adverse effects</topic><topic>Guanine - analogs & derivatives</topic><topic>Guanine - pharmacology</topic><topic>Guanine - therapeutic use</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - genetics</topic><topic>Mesothelioma</topic><topic>Mesothelioma - drug therapy</topic><topic>Mesothelioma - genetics</topic><topic>Non-small cell lung carcinoma</topic><topic>Oncology</topic><topic>original-article</topic><topic>Pemetrexed</topic><topic>Pharmacogenetics</topic><topic>Pharmacotherapy</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Properties</topic><topic>Psychopharmacology</topic><topic>Quality of life</topic><topic>Retrospective Studies</topic><topic>Small cell lung carcinoma</topic><topic>Survival Rate</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Corrigan, A</creatorcontrib><creatorcontrib>Walker, J L</creatorcontrib><creatorcontrib>Wickramasinghe, S</creatorcontrib><creatorcontrib>Hernandez, M A</creatorcontrib><creatorcontrib>Newhouse, S J</creatorcontrib><creatorcontrib>Folarin, A A</creatorcontrib><creatorcontrib>Lewis, C M</creatorcontrib><creatorcontrib>Sanderson, J 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L</au><au>Wickramasinghe, S</au><au>Hernandez, M A</au><au>Newhouse, S J</au><au>Folarin, A A</au><au>Lewis, C M</au><au>Sanderson, J D</au><au>Spicer, J</au><au>Marinaki, A M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacogenetics of pemetrexed combination therapy in lung cancer: pathway analysis reveals novel toxicity associations</atitle><jtitle>The pharmacogenomics journal</jtitle><stitle>Pharmacogenomics J</stitle><addtitle>Pharmacogenomics J</addtitle><date>2014-10-01</date><risdate>2014</risdate><volume>14</volume><issue>5</issue><spage>411</spage><epage>417</epage><pages>411-417</pages><issn>1470-269X</issn><eissn>1473-1150</eissn><abstract>Identification of polymorphisms that influence pemetrexed tolerability could lead to individualised treatment regimens and improve quality of life. Twenty-eight polymorphisms within eleven candidate genes were genotyped using the Illumina Human Exome v1.1 BeadChip and tested for their association with the clinical outcomes of non-small cell lung cancer and mesothelioma patients receiving pemetrexed/platinum doublet chemotherapy (
n
=136).
GGH
rs11545078 was associated with a reduced incidence of grade ⩾3 toxicity within the first four cycles of therapy (odds ratio (OR) 0.25,
P
=0.018), as well as reduced grade ⩾3 haematological toxicity (OR 0.13,
P
=0.048).
DHFR
rs1650697 conferred an increased risk of grade ⩾3 toxicity (OR 2.14,
P
=0.034). Furthermore,
FOLR3
rs61734430 was associated with an increased likelihood of disease progression at mid-treatment radiological evaluation (OR 4.05,
P
=0.023). Polymorphisms within
SLC19A1
(rs3788189, rs1051298 and rs914232) were associated with overall survival. This study confirms previous pharmacogenetic associations and identifies novel markers of pemetrexed toxicity.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>24732178</pmid><doi>10.1038/tpj.2014.13</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The pharmacogenomics journal, 2014-10, Vol.14 (5), p.411-417 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | 631/154/436/434 631/154/570 692/699/67/1059/99 692/699/67/1612/1350 Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - pharmacology Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biomedical and Life Sciences Biomedicine Carboplatin - adverse effects Carboplatin - therapeutic use Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - genetics Chemotherapy Cisplatin - adverse effects Cisplatin - therapeutic use Complications and side effects Dihydrofolate reductase Disease Progression Drug metabolism Drug therapy Gene Expression Genetic aspects Genetic polymorphisms Glutamates - adverse effects Glutamates - pharmacology Glutamates - therapeutic use Guanine - adverse effects Guanine - analogs & derivatives Guanine - pharmacology Guanine - therapeutic use Human Genetics Humans Lung cancer Lung Neoplasms - drug therapy Lung Neoplasms - genetics Mesothelioma Mesothelioma - drug therapy Mesothelioma - genetics Non-small cell lung carcinoma Oncology original-article Pemetrexed Pharmacogenetics Pharmacotherapy Polymorphism, Single Nucleotide - genetics Properties Psychopharmacology Quality of life Retrospective Studies Small cell lung carcinoma Survival Rate Toxicity |
| title | Pharmacogenetics of pemetrexed combination therapy in lung cancer: pathway analysis reveals novel toxicity associations |
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