Polymorphic variants of drug-metabolizing enzymes alter the risk and survival of oral cancer patients.

The present study investigated the prevalence of CYP2D64, CYP3A53 and SULT1A12, using PCR-RFLP, in normal and oral cancer (OC) patients that were stratified by OC subtype and gender. The risk of cancer, 5-year cumulative survival and hazard's ratio (HR) with respect to risk factors and clinical factors were estimated using Fisher's exact test, Kaplan-Meier analysis, and Cox proportional hazards models. CYP2D64 'GA' lowered the risk of buccal mucosa cancer (BMC) in males (OR = 0.37), whereas, 'G' allele of CYP3A53 increased risk of tongue cancer (TC) (OR = 1.67). SULT1A12 'GA' increased the risk of TC (OR = 2.36) and BMC (OR = 3.25) in females. The 5-year survival of the patients depended on factors like age, lymphovascular spread (LVS), perinodal spread (PNS), recurrence, tobacco, and alcohol. CYP3A53 'AG' and 'GG' had decreased the hazard ratio (HR) for BMC females when inflammatory infiltrate alone or along with other covariates, LVS, PNI, PNS, metastasis, recurrence, and relapse was adjusted. Similarly, CYP3A53 'AG' decreased the risk of death (HR = 0.05) when the grade was adjusted. SULT1A1*2 'GA' had decreased HR for TC males (HR = 0.08) after adjusting for inflammatory infiltrate, LVS, perineural invasion (PNI), PNS, metastasis, recurrence, and relapse. Further, our bioinformatics study revealed the presence of a CpG island within the and a CTCF binding site upstream of . Interestingly, three CpG islands and two CTCF binding sites were also identified near the . In conclusion, the SNPs altered risk and survival of BMC and TC differentially in a gender specified manner, that varied with clinical and risk factors.