Cisplatin (CDDP) chemotherapy associated with radiation (RT) has been used in head and neck squamous cell carcinoma (HNSCC) patients, and vomiting is a common side effect during treatment. This prospective study aimed to identify the roles of GSTM1 and GSTT1 (presents or nulls), GSTP1 c.313A>G, XPC c.2815A>C, XPD c.934G>A and c.2251A>C, XPF c.2505T>C, ERCC1 c.354C>T, MLH1 c.−93G>A, MSH2 c.211 + 9C>G, MSH3 c.3133G>A, EXO1 c.1765G>A, TP53 c.215G>C, CASP3 c.-1191A>G and c.-1168G>T, CASP9 c.-1339A>G, CASP8 c.-937_-932delAGTAAG, FAS c.-1378G>A and c.-671A>G, and FASL c.-157-687C>T single nucleotide polymorphisms, involved in CDDP metabolism, in vomiting severity in HNSCC patients treated with CDDP and RT.
We evaluated 88 HNSCC patients diagnosed June 2011-February 2014 which receive CDDP chemoradiation. Ondansetron and dexamethasone were administered as antiemetic therapy and evaluated using National Cancer Institute criteria. Genotypes were analyzed in genomic DNA by polymerase chain reaction based methods. The logistic regression model was used to identify variables influencing toxicities and significant results were validated using a bootstrap (bt) resampling to investigate the stability of risk estimates (1000 replications).
GSTP1 c.313AG or GG genotype alone (46.7% vs 18.6%, P = 0.004) and combined with XPD c.934GA or AA (50.0% vs 16.7%, P = 0.02; Pbt= 0.008), XPF c.2505TC or CC (52.2% vs 16.7%, P = 0.02; Pbt= 0.007) and CASP9 c.-1339AG or GG (51.9% vs 16.7%, P = 0.02; Pbt= 0.01) genotypes were more common in patients with moderate/severe vomiting than other genotypes. Carries with GSTP1 c.313AG or GG genotypes alone and combined with XPD c.934GA or AA, XPF c.2505TC or CC and CASP9 c.-1339AG or GG genotypes had 4.28, 5.00, 5.45, and 5.38 more chances of presenting moderate/severe vomiting than others.
Our data suggest, for the first time, that inherited abnormalities in DNA repair and apoptosis pathways are capable of modulating emesis in HNSCC patients under CDDP chemoradiation, and may be used for selecting patients who deserve to receive distinct doses of antiemetics or association of potent antiemetics in clinical practice.
Clinical trial identification
Legal entity responsible for the study
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
All authors have declared no conflicts of interest.