title: Genetic polymorphisms in the three malaysian races effect granisetron clinical antiemetic actions in breast cancer patients receiving chemotherapy.
abstract: BACKGROUND
  Nausea and vomiting are recognized as two separate and distinct conditions with a wide spectrum of etiologies either directly associated with cancer itself or its treatment. According to the new ranking of chemotherapy side effects, nausea is the number one or the most disturbing side effects while vomiting is the third and sometimes the fifth. The introduction of 5-HT3-recptor antagonists in the early of 1990s has revolutionized the treatment of nausea and vomiting, these agents remaining the mainstay of antiemetic therapy today. Ethnic variation (due to genetic polymorphisms) may lead to diversity in antiemetic treatment pharmacokinetic and pharmacodynamic properties, in terms of distribution, elimination, disposition and clinical effects. The aim of the 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 prospective observational study, 158 breast cancer patients treated with chemotherapy were monitored for nausea and vomiting in the first 24 hours after chemotherapy administration. The patients were then followed up again after 3 to 5 days of chemotherapy.
  
  
  RESULTS
  Genetic polymorphisms in the three races in Malaysia have significant effect on granisetron clinical antiemetic action because each is characterized by variant CYP3A4 enzymatic action.
  
  
  CONCLUSIONS
  According to the result, different type of 5-HT3 receptor antagonists, such as tropisetron and dolasetron which are predominantly metabolized by CYP2D6, should be used especially for Chinese breast cancer patients.
authors.affiliation: Clinical Pharmacy Discipline, School of Pharmaceutical Sciences, University Sains Malaysia, Minden Penang, Malaysia. bassamsunny@yahoo.com
authors.forename: Bassam Abdul Rasool
authors.initials: BA
authors.lastname: Hassan
authors.forename: Zuraidah Binti Mohd
authors.initials: ZB
authors.lastname: Yusoff
mesh_terms: D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D017829:Granisetron / Q000627:therapeutic use*; D006801:Humans; D008137:Longitudinal Studies; D008296:Malaysia; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D009367:Neoplasm Staging / Q000379:methods; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000627:therapeutic use; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D051544:Cytochrome P-450 CYP3A; D017829:Granisetron; D058831:Serotonin 5-HT3 Receptor Antagonists; C510163:CYP3A4 protein, human