title: Polymorphism in HTR3D shows different risks for acute chemotherapy-induced vomiting after anthracycline chemotherapy.
abstract: OBJECTIVE
  Serotonin (5-hydroxytryptamine 3; 5-HT(3)) receptors are involved in chemotherapy-induced nausea and vomiting (CINV), and 5-HT(3) antagonists are part of the 'gold standard' antiemetic treatment during chemotherapy. We investigated the correlation of common variants in 5-HT(3) receptor subunit genes with the occurrence of CINV.
  
  
  METHODS
  A total of 110 previously characterized chemotherapy-naive women with primary breast cancer treated with anthracycline-containing chemotherapy served as a study group for mutational analysis by direct sequencing. Eight common SNPs in the 5-HT(3) receptor genes, HTR3A, HTR3B, HTR3D and HTR3E, were selected for association analysis.
  
  
  RESULTS
  A nonsynonymous variant in HTR3D, p.G36A (rs6443930), was found to be over-represented in nonresponders, assuming a log-additive inheritance model (p = 0.048). Cox proportional regression analysis resulted in a hazards ratio of 0.36 for homozygous carriers of the C allele to vomit within 24 h after first chemotherapy administration (p = 0.049).
  
  
  CONCLUSIONS
  Our data supports the hypothesis that 5-HT(3) receptors play an important role in the pathogenesis of CINV. Along with previously identified HTR3 polymorphisms, the HTR3D p.G36A variant could also contribute to facilitating individual risk predictions.
authors.affiliation: Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hammer
authors.forename: Peter A
authors.initials: PA
authors.lastname: Fasching
authors.forename: Christian R
authors.initials: CR
authors.lastname: Loehberg
authors.forename: Claudia
authors.initials: C
authors.lastname: Rauh
authors.forename: Arif B
authors.initials: AB
authors.lastname: Ekici
authors.forename: Sebastian M
authors.initials: SM
authors.lastname: Jud
authors.forename: Mayada R
authors.initials: MR
authors.lastname: Bani
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Beckmann
authors.forename: Reiner
authors.initials: R
authors.lastname: Strick
authors.forename: Beate
authors.initials: B
authors.lastname: Niesler
mesh_terms: D000483:Alleles; D018943:Anthracyclines / Q000009:adverse effects* / Q000627:therapeutic use*; D000932:Antiemetics / Q000008:administration & dosage / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy; D020641:Polymorphism, Single Nucleotide; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics*; D012701:Serotonin / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use; D014839:Vomiting / Q000139:chemically induced* / Q000188:drug therapy / Q000235:genetics*
chemical_list: D018943:Anthracyclines; D000932:Antiemetics; C476054:HTR3D protein, human; C476055:HTR3E protein, human; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin