Genetic Polymorphisms in the Three Malaysian Races Effect Granisetron Clinical Antiemetic Actions in Breast Cancer Patients Receiving Chemotherapy


Introduction: Nausea and vomiting are recognized as two separate and distinct conditions with a widespectrum of etiologies either directly associated with cancer itself or its treatment. According to the new ranking ofchemotherapy side effects, nausea is the number one or the most disturbing side effects while vomiting is the thirdand sometimes the fifth. The introduction of 5-HT3-recptor antagonists in the early of 1990s has revolutionizedthe treatment of nausea and vomiting, these agents remaining the mainstay of antiemetic therapy today. Ethnicvariation (due to genetic polymorphisms) may lead to diversity in antiemetic treatment pharmacokinetic andpharmacodynamic properties, in terms of distribution, elimination, disposition and clinical effects. The aim ofthe present study was to clarify genetic polymorphism effects in the three main races in Malaysia i.e., Malay,Chinese and Indian, on the clinical antiemetic effects of granisetron.
Methods: In this longitudinal prospectiveobservational study, 158 breast cancer patients treated with chemotherapy were monitored for nausea andvomiting in the first 24 hours after chemotherapy administration. The patients were then followed up again after3 to 5 days of chemotherapy.
Results: Genetic polymorphisms in the three races in Malaysia have significanteffect on granisetron clinical antiemetic action because each is characterized by variant CYP3A4 enzymaticaction.
Conclusion: According to the result, different type of 5-HT3 receptor antagonists, such as tropisetronand dolasetron which are predominantly metabolized by CYP2D6, should be used especially for Chinese breastcancer patients.