For more than 200 years human
cancer induction has been known to be associated with a large variety of chemical exposures. Most exposures to chemical
carcinogens occur as a result of occupation, pollution in the ambient environment, lifestyle choices, or
pharmaceutical use. Scientific investigations have revealed that the majority of
cancer causing chemicals, or chemical
carcinogens, act through "genotoxic" or
DNA damaging mechanisms, which involve covalent binding of the chemical to
DNA (
DNA adduct formation).
Cancer-inducing exposures are typically frequent and/or chronic over years, and the accumulation of DNA damage or
DNA adduct formation is considered to be a necessary requirement for
tumor induction. Studies in animal models have indicated that the ability to reduce DNA damage will also result in reduction of
tumor risk, leading to the hypothesis that individuals having the highest levels of
DNA adducts may have an increased
cancer risk, compared to individuals with the lowest levels of
DNA adducts. Here we have reviewed twelve investigations showing 2- to 9-fold increased Relative Risks (RR) or Odds Ratios (OR) for
cancer in (the 25% of) individuals having the highest
DNA adduct levels, compared to (the 25% of) matched individuals with the lowest
DNA adducts. These studies also provided preliminary evidence that multiple types of
DNA adducts combined, or
DNA adducts combined with other risk factors (such as
infection or
inflammation), may be associated with more than 10-fold higher
cancer risks (RR = 34-60), compared to those found with a single
carcinogen. Taken together the data suggest that a reduction in human
DNA adduct level is likely to produce a reduction in human
cancer risk.