Identification of genetic polymorphisms modulating nausea and vomiting in two series of opioid-treated cancer patients
Nausea and vomiting are often associated with opioid analgesia in cancer patients; however, only a subset of patients develop such side effects. Here, we tested the hypothesis that the occurrence of nausea and vomiting is modulated by the genetic background of the patients. Whole exome sequencing of...
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| Veröffentlicht in: | Scientific reports 2020-01, Vol.10 (1), p.542, Article 542 |
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| creator | Colombo, Francesca Pintarelli, Giulia Galvan, Antonella Noci, Sara Corli, Oscar Skorpen, Frank Klepstad, Pål Kaasa, Stein Pigni, Alessandra Brunelli, Cinzia Roberto, Anna Piazza, Rocco Pirola, Alessandra Gambacorti-Passerini, Carlo Caraceni, Augusto Tommaso |
| description | Nausea and vomiting are often associated with opioid analgesia in cancer patients; however, only a subset of patients develop such side effects. Here, we tested the hypothesis that the occurrence of nausea and vomiting is modulated by the genetic background of the patients. Whole exome sequencing of DNA pools from patients with either low (n = 937) or high (n = 557) nausea and vomiting intensity, recruited in the European Pharmacogenetic Opioid Study, revealed a preliminary association of 53 polymorphisms. PCR-based genotyping of 45 of these polymorphisms in the individual patients of the same series confirmed the association for six SNPs in
AIM1L, CLCC1, MUC16, PDE3A, POM121L2
, and
ZNF165
genes. Genotyping of the same 45 polymorphisms in 264 patients of the Italian CERP study, also treated with opioids for cancer pain, instead confirmed the association for two SNPs in
ZNF568
and
PDE3A
genes. Only one SNP, rs12305038 in
PDE3A
, was confirmed in both series, although with opposite effects of the minor allele on the investigated phenotype. Overall, our findings suggest that genetic factors are indeed associated with nausea and vomiting in opioid-treated cancer patients, but the role of individual polymorphisms may be weak. |
| doi_str_mv | 10.1038/s41598-019-57358-y |
| format | Article |
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AIM1L, CLCC1, MUC16, PDE3A, POM121L2
, and
ZNF165
genes. Genotyping of the same 45 polymorphisms in 264 patients of the Italian CERP study, also treated with opioids for cancer pain, instead confirmed the association for two SNPs in
ZNF568
and
PDE3A
genes. Only one SNP, rs12305038 in
PDE3A
, was confirmed in both series, although with opposite effects of the minor allele on the investigated phenotype. Overall, our findings suggest that genetic factors are indeed associated with nausea and vomiting in opioid-treated cancer patients, but the role of individual polymorphisms may be weak.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-57358-y</identifier><identifier>PMID: 31953506</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45/23 ; 45/43 ; 631/208/514/2254 ; 631/208/727 ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Analgesia ; Analgesics, Opioid - adverse effects ; Analgesics, Opioid - therapeutic use ; Cancer ; Cancer Pain - drug therapy ; DNA sequencing ; Female ; Genetic factors ; Genotyping ; Humanities and Social Sciences ; Humans ; Male ; Middle Aged ; multidisciplinary ; Narcotics ; Nausea ; Nausea - chemically induced ; Nausea - genetics ; Opioids ; Pain perception ; Phenotypes ; Polymorphism, Single Nucleotide ; Science ; Science (multidisciplinary) ; Single-nucleotide polymorphism ; Vomiting ; Vomiting - chemically induced ; Vomiting - genetics ; Young Adult</subject><ispartof>Scientific reports, 2020-01, Vol.10 (1), p.542, Article 542</ispartof><rights>The Author(s) 2020</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-f2789fa616a1c1985e9bfa1afe37dfe8f56f506e814fe52ba4125cba5f4b9d843</citedby><cites>FETCH-LOGICAL-c474t-f2789fa616a1c1985e9bfa1afe37dfe8f56f506e814fe52ba4125cba5f4b9d843</cites><orcidid>0000-0003-4198-9620 ; 0000-0001-6058-515X ; 0000-0003-2015-4317</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969029/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969029/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31953506$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Colombo, Francesca</creatorcontrib><creatorcontrib>Pintarelli, Giulia</creatorcontrib><creatorcontrib>Galvan, Antonella</creatorcontrib><creatorcontrib>Noci, Sara</creatorcontrib><creatorcontrib>Corli, Oscar</creatorcontrib><creatorcontrib>Skorpen, Frank</creatorcontrib><creatorcontrib>Klepstad, Pål</creatorcontrib><creatorcontrib>Kaasa, Stein</creatorcontrib><creatorcontrib>Pigni, Alessandra</creatorcontrib><creatorcontrib>Brunelli, Cinzia</creatorcontrib><creatorcontrib>Roberto, Anna</creatorcontrib><creatorcontrib>Piazza, Rocco</creatorcontrib><creatorcontrib>Pirola, Alessandra</creatorcontrib><creatorcontrib>Gambacorti-Passerini, Carlo</creatorcontrib><creatorcontrib>Caraceni, Augusto Tommaso</creatorcontrib><title>Identification of genetic polymorphisms modulating nausea and vomiting in two series of opioid-treated cancer patients</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Nausea and vomiting are often associated with opioid analgesia in cancer patients; however, only a subset of patients develop such side effects. Here, we tested the hypothesis that the occurrence of nausea and vomiting is modulated by the genetic background of the patients. Whole exome sequencing of DNA pools from patients with either low (n = 937) or high (n = 557) nausea and vomiting intensity, recruited in the European Pharmacogenetic Opioid Study, revealed a preliminary association of 53 polymorphisms. PCR-based genotyping of 45 of these polymorphisms in the individual patients of the same series confirmed the association for six SNPs in
AIM1L, CLCC1, MUC16, PDE3A, POM121L2
, and
ZNF165
genes. Genotyping of the same 45 polymorphisms in 264 patients of the Italian CERP study, also treated with opioids for cancer pain, instead confirmed the association for two SNPs in
ZNF568
and
PDE3A
genes. Only one SNP, rs12305038 in
PDE3A
, was confirmed in both series, although with opposite effects of the minor allele on the investigated phenotype. Overall, our findings suggest that genetic factors are indeed associated with nausea and vomiting in opioid-treated cancer patients, but the role of individual polymorphisms may be weak.</description><subject>45/23</subject><subject>45/43</subject><subject>631/208/514/2254</subject><subject>631/208/727</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analgesia</subject><subject>Analgesics, Opioid - adverse effects</subject><subject>Analgesics, Opioid - therapeutic use</subject><subject>Cancer</subject><subject>Cancer Pain - drug therapy</subject><subject>DNA sequencing</subject><subject>Female</subject><subject>Genetic factors</subject><subject>Genotyping</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>multidisciplinary</subject><subject>Narcotics</subject><subject>Nausea</subject><subject>Nausea - chemically 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reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Colombo, Francesca</au><au>Pintarelli, Giulia</au><au>Galvan, Antonella</au><au>Noci, Sara</au><au>Corli, Oscar</au><au>Skorpen, Frank</au><au>Klepstad, Pål</au><au>Kaasa, Stein</au><au>Pigni, Alessandra</au><au>Brunelli, Cinzia</au><au>Roberto, Anna</au><au>Piazza, Rocco</au><au>Pirola, Alessandra</au><au>Gambacorti-Passerini, Carlo</au><au>Caraceni, Augusto Tommaso</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of genetic polymorphisms modulating nausea and vomiting in two series of opioid-treated cancer patients</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-01-17</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>542</spage><pages>542-</pages><artnum>542</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Nausea and vomiting are often associated with opioid analgesia in cancer patients; however, only a subset of patients develop such side effects. Here, we tested the hypothesis that the occurrence of nausea and vomiting is modulated by the genetic background of the patients. Whole exome sequencing of DNA pools from patients with either low (n = 937) or high (n = 557) nausea and vomiting intensity, recruited in the European Pharmacogenetic Opioid Study, revealed a preliminary association of 53 polymorphisms. PCR-based genotyping of 45 of these polymorphisms in the individual patients of the same series confirmed the association for six SNPs in
AIM1L, CLCC1, MUC16, PDE3A, POM121L2
, and
ZNF165
genes. Genotyping of the same 45 polymorphisms in 264 patients of the Italian CERP study, also treated with opioids for cancer pain, instead confirmed the association for two SNPs in
ZNF568
and
PDE3A
genes. Only one SNP, rs12305038 in
PDE3A
, was confirmed in both series, although with opposite effects of the minor allele on the investigated phenotype. Overall, our findings suggest that genetic factors are indeed associated with nausea and vomiting in opioid-treated cancer patients, but the role of individual polymorphisms may be weak.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31953506</pmid><doi>10.1038/s41598-019-57358-y</doi><orcidid>https://orcid.org/0000-0003-4198-9620</orcidid><orcidid>https://orcid.org/0000-0001-6058-515X</orcidid><orcidid>https://orcid.org/0000-0003-2015-4317</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Scientific reports, 2020-01, Vol.10 (1), p.542, Article 542 |
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| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry; Springer Nature OA Free Journals |
| subjects | 45/23 45/43 631/208/514/2254 631/208/727 Adolescent Adult Aged Aged, 80 and over Analgesia Analgesics, Opioid - adverse effects Analgesics, Opioid - therapeutic use Cancer Cancer Pain - drug therapy DNA sequencing Female Genetic factors Genotyping Humanities and Social Sciences Humans Male Middle Aged multidisciplinary Narcotics Nausea Nausea - chemically induced Nausea - genetics Opioids Pain perception Phenotypes Polymorphism, Single Nucleotide Science Science (multidisciplinary) Single-nucleotide polymorphism Vomiting Vomiting - chemically induced Vomiting - genetics Young Adult |
| title | Identification of genetic polymorphisms modulating nausea and vomiting in two series of opioid-treated cancer patients |
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