Polymorphisms in the novel serotonin receptor subunit gene HTR3C show different risks for acute chemotherapy-induced vomiting after anthracycline chemotherapy

Fasching, Peter A.; Kollmannsberger, B.; Strissel, Pamela L.; Niesler, Beate; Engel, Jasper; Kreis, Henning; Lux, Michael P.; Weihbrecht, Sebastian; Lausen, Berthold; Bani, M. R.; Beckmann, Matthias W.; Strick, Reiner

doi:10.1007/s00432-008-0387-1

Cited by 53 publications

(71 citation statements)

References 15 publications

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“…It has been shown that ondansetron is mainly metabolized by CYP1A2, CYP2D6 and CYP3A4 (15). Finally, other studies suggested that variation of 5-HT3B, 5-HT3C and 5-HTR3D receptors could be the predictors of 5-HT3RAs' efficacy in cancer patients (16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Association of ABCB1, 5-HT3B Receptor and CYP2D6 Genetic Polymorphisms with Ondansetron and Metoclopramide Antiemetic Response in Indonesian Cancer Patients Treated with Highly Emetogenic Chemotherapy

Perwitasari¹,

Wessels²,

Straaten³

et al. 2011

Japanese Journal of Clinical Oncology

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Objective: Suboptimal treatment of chemotherapy-induced nausea and vomiting and unsatisfactory response to antiemetic drugs cause impairment of cancer patient's daily functioning. This study was aimed to investigate the association of selected germline polymorphisms with ondansetron and metoclopramide response in Indonesian cancer patients treated with highly emetogenic chemotherapy. Methods: We enrolled 202 chemotherapy naïve patients treated with cisplatin at a dosage of !50 mg/m 2 as monotherapy or as combined chemotherapy. Ondansetron 8 mg and dexamethasone 8 mg intravenously were the standard antiemetic therapy for prevention of acute chemotherapy-induced nausea and vomiting. Metoclopramide 10 mg orally, three times per day as fixed prescription, was given until 5 days after chemotherapy to prevent delayed chemotherapy-induced nausea and vomiting. Primary and secondary outcomes were the occurrence of chemotherapy-induced nausea and vomiting in the acute and delayed phase. The following single-nucleotide polymorphisms were determined in ABCB1: rs1045642, rs2032582 and rs1128503; in 5-HT3B-R: rs45460698, rs4938058 and rs7943062; and in CYP2D6: rs16947 (CYP2D6*2), rs3892097 (CYP2D6*4) and rs1065852 (CYP2D6*10) using Taqman assays. Results: During the acute phase, 21.8 and 30.2% patients experienced Grade 3 and 4 nausea and vomiting, respectively, whereas 38.6% patients experienced nausea and/or vomiting in the delayed phase. Carriers of the CTG haplotype of the ABCB1 gene experienced Grade 3 and 4 chemotherapy-induced nausea and vomiting more often than other haplotypes in the delayed phase (P , 0.05). No associations were found with the 5-HT3B receptor haplotypes and CYP2D6-predicted phenotypes. Conclusions: Our study shows that in Indonesian cancer patients treated with highly cytostatic emetogenic, carriership of the CTG haplotype of the ABCB1 gene is related to an increased risk of delayed chemotherapy-induced nausea and vomiting.

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Section: Introductionmentioning

confidence: 99%

Association of ABCB1, 5-HT3B Receptor and CYP2D6 Genetic Polymorphisms with Ondansetron and Metoclopramide Antiemetic Response in Indonesian Cancer Patients Treated with Highly Emetogenic Chemotherapy

Perwitasari¹,

Wessels²,

Straaten³

et al. 2011

Japanese Journal of Clinical Oncology

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“…In the present analysis, however, our results of rs6766410 (HTR3C) and rs4680 (COMT) were inconsistent with the previous findings, which CINV occurred in 50% of the patients with C/C homozygosity of rs6766410 (HTR3C), compared to 19% of those with A/A homozygosity and 22% of those with A/C heterozygosity. 8) Further, COMT activity in G/G homozygotes on rs4680 was approximately 3 to 4 times higher than that in A/A homozygotes.…”

Section: Discussionmentioning

confidence: 99%

“…Analysis of gene polymorphisms such as those in the serotonin 5-HT 3A receptor, 7) 5-HT 3B receptor, 6) 5-HT 3C receptor, 8) cytochrome P-450 2D6, 33) and P-glycoprotein 34) for the purpose of investigating whether genetic factors influence the efficacy of the antiemetic agents used for CINV revealed that certain gene polymorphisms were associated with nausea and vomiting. However, there have been no studies to investigate the association between gene polymorphisms and the efficacy of antiemetic therapies on CINV in Japanese cancer patients.…”

Section: Discussionmentioning

confidence: 99%

“…To that end, some polymorphisms in the serotonin 5-HT 3 receptor genes were investigated for their relationship with CINV. [6][7][8] There is also the possibility that polymorphisms of genes that play functional molecular or physiological roles, such as the NK-1 receptor, dopamine D 2 receptor, and catechol-O-methyltransferase (COMT), are related to CINV. [9][10][11][12] The likelihood that nausea and vomiting will develop after chemotherapy depends on other many factors as well.…”

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confidence: 99%

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An Analysis of Behavioral and Genetic Risk Factors for Chemotherapy-Induced Nausea and Vomiting in Japanese Subjects

Mukoyama

Yoshimi

Goto

et al. 2016

Biological & Pharmaceutical Bulletin

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There are individual differences in the frequency of chemotherapy-induced nausea and vomiting (CINV) in cancer patients. We investigated the individual variability in susceptibility to CINV with focus on both behavioral factors and genetic factors in Japanese cancer patients. We performed a prospective study to investigate the association between patient attributes (backgrounds and habits as well as gene polymorphisms) and anorexia, nausea, or vomiting in 55 Japanese cancer patients undergoing chemotherapy at Nagoya University Hospital. We found that gender (female), use of non-steroidal anti-inflammatory drugs, susceptibility to motion sickness, and anxiety were associated with the frequency of CINV. Gene polymorphisms of rs1076560 (dopamine D 2 receptor gene), rs6766410 (serotonin 5-HT 3C receptor gene) and rs4680 (catechol-Omethyltransferase gene) were also associated. Our data suggest that these attributes may thus be risk factors for CINV. Our results provide novel information that can be used to predict the incidence of CINV in Japanese patients undergoing chemotherapy; this can help provide a substantial improvement in supportive care for patients with different types of cancer.Key words chemotherapy; anorexia; nausea; vomiting; gene polymorphism; risk factor Chemotherapy-induced nausea and vomiting (CINV) is one of the most distressing side effects of chemotherapy. Inadequately controlled emesis impairs functional activity and QOL for patients, increases the use of health care resources, and may occasionally compromise adherence to treatment.1,2) According to the American Society of Clinical Oncology Clinical Practice Guidelines regarding antiemetic agents in oncology, a three-drug combination of a serotonin 5-hydroxytryptamine type 3 (5-HT 3 ) receptor antagonist, dexamethasone, and aprepitant is recommended before chemotherapy treatments that have high emetic risks. If this is insufficient, substituting a high-dose of intravenous metoclopramide for the serotonin 5-HT 3 receptor antagonist or adding a dopamine D 2 receptor antagonist to the regimen is considered. 3,4) In recent years, a new class of antiemetic therapies represented by neurokinin-1 (NK-1) receptor antagonists has been introduced into clinical practice. An NK-1 receptor antagonist, aprepitant, combined with dexamethasone and the serotonin 5-HT 3 receptor antagonist ondansetron, have been shown to ameliorate CINV in both high and moderate emetic risk chemotherapy patients. 4,5) In spite of antiemetic therapy being administered according to the guidelines for CINV treatment, an incidence rate of 25-38% for delayed emesis and 55-60% for delayed nausea has been observed.4) The mechanisms underlying interpatient variability in response to treatment are not clear but are believed to be due, in part, to genetic factors. To that end, some polymorphisms in the serotonin 5-HT 3 receptor genes were investigated for their relationship with CINV. [6][7][8] There is also the possibility that polymorphisms of genes that play functional molecular or phys...

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“…Fasching et al reported an association of the HTR3C p.163N allele with the occurrence of vomiting in breast cancer patients undergoing chemotherapy (p = 0.009) [16]. In a different study, a homozygous deletion in the promoter region of the HTR3B gene, c.-104_-102del-AGA, present in only 1.2% of 242 patients, involved a higher probability of acute emesis (p = 0.008) [17].…”

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confidence: 95%

Polymorphism in HTR3D Shows Different Risks for Acute Chemotherapy-Induced Vomiting After Anthracycline Chemotherapy

Hammer

Fasching²,

Loehberg³

et al. 2010

Pharmacogenomics

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Polymorphisms in the novel serotonin receptor subunit gene HTR3C show different risks for acute chemotherapy-induced vomiting after anthracycline chemotherapy

Cited by 53 publications

References 15 publications

Association of ABCB1, 5-HT3B Receptor and CYP2D6 Genetic Polymorphisms with Ondansetron and Metoclopramide Antiemetic Response in Indonesian Cancer Patients Treated with Highly Emetogenic Chemotherapy

Association of ABCB1, 5-HT3B Receptor and CYP2D6 Genetic Polymorphisms with Ondansetron and Metoclopramide Antiemetic Response in Indonesian Cancer Patients Treated with Highly Emetogenic Chemotherapy

An Analysis of Behavioral and Genetic Risk Factors for Chemotherapy-Induced Nausea and Vomiting in Japanese Subjects

Polymorphism in HTR3D Shows Different Risks for Acute Chemotherapy-Induced Vomiting After Anthracycline Chemotherapy

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