The Molecular Epidemiology of DNA Repair Polymorphisms in Carcinogenesis

There are well-established examples of highly penetrant mutations in genes that are directly involved in carcinogenesis and result in a high risk of cancer in the individuals who carry these mutations. Some of the best examples include syndromes of defective DNA repair, such as xeroderma pigmentosum [1]. However, these examples tend to be very rare and thus contrib‐ ute minimally to the overall burden of cancer risk. Nevertheless, it has long been suspected that less penetrant susceptibility may be produced by much more common variants in the same cancer-related genes, for example, in the form of single nucleotide polymorphisms (SNPs), that presumably would be less disruptive and therefore produce more subtle effects on the function of the encoded proteins but which could contribute greatly to overall cancer attributable risk in populations due to their widespread occurrence [1]. Because several of these common polymorphisms occur in DNA repair proteins, many epidemiologic studies have examined their relationship to cancer risk [2-4].