Molecular epidemiology has made great progress in detecting and documenting carcinogenic exposures and host susceptibility factors, in an effort to explain interindividual variation in disease. Interindividual differences in
cancer risk have been hypothesized to result from an array of both genetic and acquired factors including nutritional status. Elevated risk of
lung cancer has been associated with polymorphisms of metabolic genes such as
CYP1A1 and GSTM1. On the other hand, numerous studies have demonstrated that diets rich in fruits and vegetables are protective against
cancer, and have correlated high levels of
antioxidants in the blood with decreased risk. As a first step in identifying susceptible individuals, we have assessed the combined effect of genetic factors and nutritional status on
DNA adducts in a population of healthy smokers. Plasma
retinol,
beta-carotene,
alpha-tocopherol, and
zeaxanthin were inversely correlated with DNA damage, especially in subjects lacking the "protective" GSTM1 gene. Research is ongoing using
biomarkers to determine the effect of supplementation with
antioxidants/
vitamins on DNA damage, especially in population subsets with putative "at risk" genotypes. Information on mechanisms of interactions between exposure,
micronutrients, and other susceptibility factors is important in the development of effective practical interventions.