title: Genetic variants in nicotine addiction and alcohol metabolism genes, oral cancer risk and the propensity to smoke and drink alcohol: a replication study in India.
abstract: BACKGROUND
  Genetic variants in nicotinic acetylcholine receptor and alcohol metabolism genes have been associated with propensity to smoke tobacco and drink alcohol, respectively, and also implicated in genetic susceptibility to head and neck cancer. In addition to smoking and alcohol, tobacco chewing is an important oral cancer risk factor in India. It is not known if these genetic variants influence propensity or oral cancer susceptibility in the context of this distinct etiology.
  
  
  METHODS
  We examined 639 oral and pharyngeal cancer cases and 791 controls from two case-control studies conducted in India. We investigated six variants known to influence nicotine addiction or alcohol metabolism, including rs16969968 (CHRNA5), rs578776 (CHRNA3), rs1229984 (ADH1B), rs698 (ADH1C), rs1573496 (ADH7), and rs4767364 (ALDH2).
  
  
  RESULTS
  The CHRN variants were associated with the number of chewing events per day, including in those who chewed tobacco but never smoked (P =  0.003, P =  0.01 for rs16969968 and rs578776 respectively). Presence of the variant allele contributed to approximately 13% difference in chewing frequency compared to non-carriers. While no association was observed between rs16969968 and oral cancer risk (OR =  1.01, 95% CI =  0.83- 1.22), rs578776 was modestly associated with a 16% decreased risk of oral cancer (OR =  0.84, 95% CI =  0.72- 0.98). There was little evidence for association between polymorphisms in genes encoding alcohol metabolism and oral cancer in this population.
  
  
  CONCLUSIONS
  The association between rs16969968 and number of chewing events implies that the effect on smoking propensity conferred by this gene variant extends to the use of smokeless tobacco.
authors: Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
authors: Devasena
authors: D
authors: Anantharaman
authors: Genetic Cancer Susceptibility Group, International Agency for Research on Cancer, Lyon, France.
authors: Amélie
authors: A
authors: Chabrier
authors: Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
authors: Valérie
authors: V
authors: Gaborieau
authors: Infections and Cancer Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
authors: Silvia
authors: S
authors: Franceschi
authors: Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, France.
authors: Rolando
authors: R
authors: Herrero
authors: Department of Molecular Oncology, Cancer Institute, Chennai, India.
authors: Thangarajan
authors: T
authors: Rajkumar
authors: Mahimkar Lab, Advanced Center for Treatment Research and Education in Cancer, Tata Memorial Center, Navi Mumbai, India.
authors: Tanuja
authors: T
authors: Samant
authors: Mahimkar Lab, Advanced Center for Treatment Research and Education in Cancer, Tata Memorial Center, Navi Mumbai, India.
authors: Manoj B
authors: MB
authors: Mahimkar
authors: Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
authors: Paul
authors: P
authors: Brennan
authors: Genetic Cancer Susceptibility Group, International Agency for Research on Cancer, Lyon, France.
authors: James D
authors: JD
authors: McKay
mesh_terms: D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000428:Alcohol Drinking / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D016022:Case-Control Studies; D000431:Ethanol / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011978:Receptors, Nicotinic / Q000235:genetics; D012307:Risk Factors; D014029:Tobacco Use Disorder / Q000453:epidemiology / Q000235:genetics*
chemical_list: D011978:Receptors, Nicotinic; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase