title: Gender specific association of TP53 polymorphisms (EX4 215G>C Arg72Pro, IVS3+40-41ins16, and IVS6+62G>A), with risk of oral cancer subtypes and overall survival of the patients.
abstract: Reports on the association of TP53 polymorphisms with oral cancer are not only limited but also not specific to site and/or gender. Hence, we examined the effect of TP53 polymorphisms (EX4 215G>C, IVS3+40-41ins16 and IVS6+62G>A) on buccal mucosa cancer (BMC) and tongue cancer (TC) risk, survival of patients in relation to risk and clinical factors, gender wise (excepting for estimating hazards ratio [HR]), using Fisher's Exact Test, Kaplan-Meier analysis, and Cox-proportional hazards models. The exonic polymorphism increased BMC and TC risk in males by 2-4-fold. The IVS3+40-41ins16 was protective against BMC and TC in both genders, whereas IVS6+62G>A protected only males against TC. Genotype combinations and haplotypes which altered the risk of cancers in males and females were different. TC males, aged 40-44 years and females, aged 55-59 years survived better than BMC patients. The IVS3+40-41ins16 polymorphism differentially impacted survival of female patients exposed to tobacco. TC patients with EX4 215GC with lymphovascular spread (LVS) and metastasis exhibited higher HR while, patients with EX4 215CC and perineural invasion (PNI) showed lower HR. Impact of the intronic variants along with clinical parameters on survival and HR estimates varied between BMC and TC. Our bioinformatics analysis revealed the presence of CTCF binding site within TP53 gene. In conclusion, the polymorphisms altered risk and survival of BMC and TC in a gender specific manner, which varied with mode of tobacco and/or alcohol use. The current study, therefore underscores strong need for research, stratified by tumor site and gender. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Indo-American Cancer Research Foundation, Formerly Research and Development, Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad, Telangana, India.|Acharya Nagarjuna University, Andhra Pradesh, India.
authors.forename: Srivani L S S
authors.initials: SL
authors.lastname: Nagam
authors.affiliation: Indo-American Cancer Research Foundation, Formerly Research and Development, Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad, Telangana, India.
authors.forename: Saritha
authors.initials: S
authors.lastname: Katta
authors.affiliation: Indo-American Cancer Research Foundation, Formerly Research and Development, Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad, Telangana, India.
authors.forename: Vidudala V T S
authors.initials: VV
authors.lastname: Prasad
mesh_terms: D000328:Adult; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D019295:Computational Biology / Q000379:methods; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology*; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009362:Neoplasm Metastasis; D011110:Polymorphism, Genetic; D012097:Repressor Proteins / Q000378:metabolism; D012307:Risk Factors; D012737:Sex Factors; D016019:Survival Analysis; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D012097:Repressor Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: TP53 polymorphisms; buccal mucosa and tongue cancers; hazards ratio; overall survival; risk