Human Variation in DNA Repair, Immune Function, and Cancer Risk

DNA damage constantly threatens genome integrity, and DNA repair deficiency is associated with increased cancer risk. An intuitive and widely accepted explanation for this relationship is that unrepaired DNA damage leads to carcinogenesis due to the accumulation of mutations in somatic cells. But DNA repair also plays key roles in the function of immune cells, and immunodeficiency is an important risk factor for many cancers. Thus, it is possible that emerging links between inter-individual variation in DNA repair capacity and cancer risk are driven, at least in part, by variation in immune function, but this idea is underexplored. In this review we present an overview of the current understanding of the links between cancer risk and both inter-individual variation in DNA repair capacity and inter-individual variation in immune function. We discuss factors that play a role in both types of variability, including age, lifestyle, and environmental exposures. In conclusion, we propose a research paradigm that incorporates functional studies of both genome integrity and the immune system to predict cancer risk and lay the groundwork for personalized prevention.