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Abstract
BackgroundGenetic 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.MethodsWe 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).ResultsThe 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.ConclusionThe 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.
Highlights
Cancers of the oral cavity and pharynx contribute to nearly 400,000 new cases each year worldwide, more than half of which occur in India
In this study we aimed to (i) determine whether the association between CHRN variants and propensity to smoke extends to nonsmoking forms of tobacco use (ii) examine if CHRN genetic variants influence susceptibility to oral cancer risk in India, (iii) clarify the association between the potential causal variants in the 4q23 (ADH) and 12q (ALDH2) locus and the risk of oral cancer in India
Of the 639 cases and 791 controls included in the present analysis, the International Agency for Research on Cancer (IARC) international study contributed the largest proportion of subjects (61%)
Summary
Cancers of the oral cavity and pharynx contribute to nearly 400,000 new cases each year worldwide, more than half of which occur in India. Lung cancer GWAS and nicotine addiction studies have identified the 15q25 locus harbouring the nicotinic acetylcholine receptor (CHRN) gene cluster [6,7,8]. Alcohol is an important and established risk factor for oral cancer in India [21,22,23,24], there is a paucity of data on the association of ADH and ALDH2 variants in this population. Genetic variants in nicotinic acetylcholine receptor and alcohol metabolism genes have been associated with propensity to smoke tobacco and drink alcohol, respectively, and 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
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