title: Influence of the CYP1A1 T3801C Polymorphism on Tobacco and Alcohol-Associated Head and Neck Cancer Susceptibility in Northeast India.
abstract: BACKGROUND
  Tobacco and alcohol contain or may generate carcinogenic compounds related to cancers. CYP1A1 enzymes act upon these carcinogens before elimination from the body. The aim of this study was to investigate whether CYP1A1 T3801C polymorphism modulates the relationship between tobacco and alcohol- associated head and neck cancer (HNC) susceptibility among the northeast Indian population.
  
  
  METHODS
  One hundred and seventy histologically confirmed HNC cases and 230 controls were included within the study. The CYP1A1 T3801C polymorphism was determined using PCR-RFLP, and the results were confirmed by DNA sequencing. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approaches were applied for statistical analysis.
  
  
  RESULTS
  The CYP1A1 CC genotype was significantly associated with HNC risk (P=0.045). A significantly increased risk of HNC (OR=6.09; P<0.0001) was observed in individuals with combined habits of smoking, alcohol drinking and tobacco-betel quid chewing. Further, gene-environment interactions revealed enhanced risks of HNC among smokers, alcohol drinkers and tobacco-betel quid chewers carrying CYP1A1 TC or CC genotypes. The highest risk of HNC was observed among smokers (OR=7.55; P=0.009) and chewers (OR=10.8; P<0.0001) carrying the CYP1A1 CC genotype. In MDR analysis, the best model for HNC risk was the three-factor model combination of smoking, tobacco-betel quid chewing and the CYP1A1 variant genotype (CVC=99/100; TBA=0.605; P<0.0001); whereas interaction entropy graphs showed synergistic interaction between tobacco habits and CYP1A1.
  
  
  CONCLUSIONS
  Our results confirm that the CYP1A1 T3801C polymorphism modifies the risk of HNC and further demonstrated importance of gene-environment interaction.
authors.affiliation: Molecular Medicine Laboratory, Department of Biotechnology, Assam University, Silchar, Assam, India E-mail : drsankarghosh@gmail.com.
authors.forename: Seram Anil
authors.initials: SA
authors.lastname: Singh
authors.forename: Javed Hussain
authors.initials: JH
authors.lastname: Choudhury
authors.forename: Wetetsho
authors.initials: W
authors.lastname: Kapfo
authors.forename: Sharbadeb
authors.initials: S
authors.lastname: Kundu
authors.forename: Bishal
authors.initials: B
authors.lastname: Dhar
authors.forename: Shaheen
authors.initials: S
authors.lastname: Laskar
authors.forename: Raima
authors.initials: R
authors.lastname: Das
authors.forename: Manish
authors.initials: M
authors.lastname: Kumar
authors.forename: Sankar Kumar
authors.initials: SK
authors.lastname: Ghosh
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects / Q000453:epidemiology*; D001114:Areca / Q000009:adverse effects; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D058011:Multifactor Dimensionality Reduction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology*
chemical_list: C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1