Polymorphisms in GSTM1 and XPD genes predict clinical outcome in advanced oral cancer patients treated with postoperative radiotherapy.
Polymorphisms in metabolic and DNA repair genes may alter protein function, consequently affecting patients' response to chemo/radiotherapy. We retrospectively assessed whether polymorphisms of glutathione-S-transferase genes GSTM1 (deletion), GSTT1 (deletion), GSTP1 (Ile105Val, rs1695), and DNA repair genes hOGG1 (Ser326Cys, rs1052133), XRCC1 (Arg194Trp, rs1799782, and Arg399Gln, rs25487), XPD (Asp312Asn, rs1799793, and Lys751Gln, rs13181) can predict clinical outcome in 187 oral squamous cell carcinoma patients treated with postoperative radiotherapy. The Cox proportional hazards model was used to evaluate the role of polymorphic genotypes on relapse-free (RFS) and disease-specific (DSS) survival. Deletion polymorphism of GSTM1 gene was significantly associated with DSS. The rs1799793 variant allele showed significant protection in both DSS and RFS. Significant increase in RFS but not in DSS was observed with polymorphic rs13181. The combined analysis of GSTM1 and XPD polymorphisms revealed favorable effect on survival. GSTM1 and XPD variant alleles, independently as well as in combination may serve as important predictors of clinical outcome in radiotherapy-treated OSCC patients.
Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India. mmahimkar@actrec.gov.in
Manoj B
MB
Mahimkar
Tanuja A
TA
Samant
Sadhana
S
Kannan
Jatin
J
Tulsulkar
Prathamesh S
PS
Pai
Devasena
D
Anantharaman
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000532:radiotherapy* / Q000601:surgery; D045647:DNA Glycosylases / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000532:radiotherapy* / Q000601:surgery; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*; D055815:Young Adult
D045647:DNA Glycosylases; D004268:DNA-Binding Proteins; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein; C000619371:XRCC1 protein, human; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; C479058:oxoguanine glycosylase 1, human; C497292:ERCC2 protein, human