Polymorphism in HTR3D shows different risks for acute chemotherapy-induced vomiting after anthracycline chemotherapy.
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.
Hammer
Christian
C
Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
Fasching
Peter A
PA
Loehberg
Christian R
CR
Rauh
Claudia
C
Ekici
Arif B
AB
Jud
Sebastian M
SM
Bani
Mayada R
MR
Beckmann
Matthias W
MW
Strick
Reiner
R
Niesler
Beate
B
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*
D018943:Anthracyclines; D000932:Antiemetics; C476054:HTR3D protein, human; C476055:HTR3E protein, human; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin