Environmental factors as regulators and effectors of multistep carcinogenesis

This review highlights current knowledge of environmental factors in carcin ogenesis and their cellular targets. The hypothesis that environmental fact ors influence carcinogenesis is widely supported by both epidemiological an d experimental studies. The fact that only a small fraction of cancers can be attributed to germline mutations in cancer-related genes further buttres ses the importance of environmental factors in carcinogenesis, Furthermore, penetrance of germline mutations may be modified by either environmental o r other genetic factors. Examples of environmental factors that have been a ssociated with increased cancer risk in the human population include chemic al and physical mutagens (e.g. cigarette smoke, heterocyclic amines, asbest os and UV irradiation), infection by certain viral or bacterial pathogens, and dietary nongenotoxic constituents (e.g. macro- and micronutrients), Amo ng molecular targets of environmental influences on carcinogenesis are soma tic mutation (genetic change) and aberrant DNA methylation (epigenetic chan ge) at the genomic level and post-translational modifications at the protei n level. At both levels, changes elicited affect either the stability or th e activity of key regulatory proteins, including oncoproteins and tumor sup pressor proteins. Together, via multiple genetic and epigenetic lesions, en vironmental factors modulate important changes in the pathway of cellular c arcinogenesis.