Assessment of genotoxic and molecular mechanisms of cancer risk in smoking and smokeless tobacco users

• Chromosome aberrations and micronucleus were higher in smokeless tobacco users.
• High levels of DNA damage was found in smokeless tobacco users.
• Homozygous variants of XRCC1 and p53 genes were found among tobacco users.
• XRCC1 and p53 variants are associated with cancer risk.

Inexpensive forms of tobacco are widely used in developing countries such as India. We have evaluated genotoxicity endpoints (chromosome aberrations, micronucleus frequency, comet assay) and polymorphisms of the XRCC1 and p53 genes among smokers and smokeless tobacco (SLT) users in rural Tamilnadu, South India. Cytogenetic, DNA damage and SNP analyses were performed on peripheral blood samples; micronucleus frequency was measured in peripheral blood and buccal mucosa exfoliated cells. Both categories of tobacco users had elevated levels of genotoxic damage. SNP analysis of tobacco users revealed that 17% carry the XRCC1 gln399gln genotype and 19% carry the p53 pro72pro genotype. Both genotypes are associated with increased risk of cancer.