Abstract
The present study investigated the prevalence of CYP2D6*4, CYP3A5*3 and SULT1A1*2, 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. CYP2D6*4 ‘GA’ lowered the risk of buccal mucosa cancer (BMC) in males (OR = 0.37), whereas, ‘G’ allele of CYP3A5*3 increased risk of tongue cancer (TC) (OR = 1.67). SULT1A1*2 ‘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. CYP3A5*3 ‘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, CYP3A5*3 ‘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 CYP2D6 and a CTCF binding site upstream of CYP2D6. Interestingly, three CpG islands and two CTCF binding sites were also identified near the SULT1A1. 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.
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Acknowledgements
The research was funded by Basavatarakam Indo-American Cancer Hospital & Research Institute (BIACH & RI). Mrs. Sarika is thankful to Council of Scientific and Industrial Research (CSIR), Government of India for the award of Junior Research Fellow and to Acharya Nagarjuna University, Nagarjuna Nagar, AP, India for registering Mrs. Sarika for her doctoral degree. We also express our deep gratitude to Dr. V.V.T.S. Prasad for the invaluable help provided during the study. The authors would like to thank the Institute’s administration and the medical team for help during the study. The authors also acknowledge the help provided by N. Sateesh and N.L.S.S. Srivani for their assistance in collecting the data.
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KP conceptualized and reviewed the manuscript. SD designed the analysis, conducted the experiments, collected the data, performed the statistical analysis, and prepared the manuscript.
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Daripally, S., Peddi, K. Polymorphic variants of drug-metabolizing enzymes alter the risk and survival of oral cancer patients. 3 Biotech 10, 529 (2020). https://doi.org/10.1007/s13205-020-02526-5
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DOI: https://doi.org/10.1007/s13205-020-02526-5