Association of polymorphisms in proinflammatory cytokine genes with the development of oral cancer in Southern Thailand

Oral squamous cell carcinoma (OSCC) is highly prevalent in southeastern Asia suggesting that region-specific environmental and biological factors contribute to the development of this cancer. Exposure to oral carcinogens (i.e. betel quid) and pathogenic agents (i.e. papilloma virus) is common among individuals that develop OSCC in countries such as Thailand, India etc. However, not all individuals with such exposures develop the disease suggesting that other factors further increase susceptibility to OSCC. It is therefore plausible that functional variants in DNA repair genes and/or genes controlling inflammation and immunological response play a role in determining susceptibility to OSCC. Previous studies (including ours) have found an association between variants in DNA repair genes and increased susceptibility to OSCC. By extension, the current study examined the association between SNPs in genes encoding proteins involved in inflammation and immunomodulation (IL1alpha, IL1beta, IL8, TNFalpha) and OSCC. A total of 107 cases and 157 controls were analyzed. OSCC cases were more likely to carry the "T" allele at the IL1alpha(+4845) SNP than controls (OR=2.0, 1.0-4.4). OSCC cases that smoke and drink were more likely to carry either the "T" allele at the IL1beta(+3953) SNP (OR=10.4, 1.1-93.2) or the "C" allele at the TNFalpha(-1031) SNP (OR=3.4, 1.0-11.4) than controls. These results support the hypothesis that variants in inflammatory or immunomodulatory genes influence susceptibility to OSCC in Thailand. Larger studies are needed to confirm these results and more importantly to properly investigate the complex interactions among genetic variants in DNA repair and inflammation and other non-genetic susceptibility factors. In addition, laboratory experiments designed to determine the functional properties of the genetic variants are needed.