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Identification of genetic polymorphisms modulating nausea and vomiting in two series of opioid-treated cancer patients.
Scientific Reports ( IF 3.8 ) Pub Date : 2020-01-17 , DOI: 10.1038/s41598-019-57358-y Francesca Colombo 1 , Giulia Pintarelli 1 , Antonella Galvan 1 , Sara Noci 1 , Oscar Corli 2 , Frank Skorpen 3, 4 , Pål Klepstad 3, 5 , Stein Kaasa 3, 6 , Alessandra Pigni 1 , Cinzia Brunelli 1 , Anna Roberto 2 , Rocco Piazza 7 , Alessandra Pirola 7 , Carlo Gambacorti-Passerini 7 , Augusto Tommaso Caraceni 1
Scientific Reports ( IF 3.8 ) Pub Date : 2020-01-17 , DOI: 10.1038/s41598-019-57358-y Francesca Colombo 1 , Giulia Pintarelli 1 , Antonella Galvan 1 , Sara Noci 1 , Oscar Corli 2 , Frank Skorpen 3, 4 , Pål Klepstad 3, 5 , Stein Kaasa 3, 6 , Alessandra Pigni 1 , Cinzia Brunelli 1 , Anna Roberto 2 , Rocco Piazza 7 , Alessandra Pirola 7 , Carlo Gambacorti-Passerini 7 , Augusto Tommaso Caraceni 1
Affiliation
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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.
中文翻译：
在两个系列阿片类药物治疗的癌症患者中鉴定出调节恶心和呕吐的遗传多态性。
恶心和呕吐通常与癌症患者的阿片类镇痛有关。但是，只有一部分患者会出现这种副作用。在这里，我们测试了这样的假设：恶心和呕吐的发生是由患者的遗传背景调节的。欧洲药物遗传阿片类药物研究中招募的恶心和呕吐强度低（n = 937）或高（n = 557）患者的DNA库的整体外显子组测序揭示了53种多态性的初步关联。在同一系列的个体患者中，基于PCR的45种多态性基因分型证实了AIM1L，CLCC1，MUC16，PDE3A，POM121L2和ZNF165基因中的六个SNP关联。意大利CERP研究对264位患者进行了相同的45个多态性的基因分型，并用阿片类药物治疗了癌痛，相反，证实了ZNF568和PDE3A基因中两个SNP的关联。在两个系列中仅确认了一个SNP，即rs12305038，尽管次要等位基因对所研究的表型具有相反的作用，但在两个系列中均被证实。总体而言，我们的发现表明，遗传因素确实与阿片类药物治疗的癌症患者的恶心和呕吐有关，但个体多态性的作用可能较弱。
更新日期：2020-01-17
中文翻译：
在两个系列阿片类药物治疗的癌症患者中鉴定出调节恶心和呕吐的遗传多态性。
恶心和呕吐通常与癌症患者的阿片类镇痛有关。但是，只有一部分患者会出现这种副作用。在这里，我们测试了这样的假设：恶心和呕吐的发生是由患者的遗传背景调节的。欧洲药物遗传阿片类药物研究中招募的恶心和呕吐强度低（n = 937）或高（n = 557）患者的DNA库的整体外显子组测序揭示了53种多态性的初步关联。在同一系列的个体患者中，基于PCR的45种多态性基因分型证实了AIM1L，CLCC1，MUC16，PDE3A，POM121L2和ZNF165基因中的六个SNP关联。意大利CERP研究对264位患者进行了相同的45个多态性的基因分型，并用阿片类药物治疗了癌痛，相反，证实了ZNF568和PDE3A基因中两个SNP的关联。在两个系列中仅确认了一个SNP，即rs12305038，尽管次要等位基因对所研究的表型具有相反的作用，但在两个系列中均被证实。总体而言，我们的发现表明，遗传因素确实与阿片类药物治疗的癌症患者的恶心和呕吐有关，但个体多态性的作用可能较弱。
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