Toward the last cohort.

Two essential elements contribute to the risk of all diseases, especially cancer: genetic variation and environmental exposures. The completion of a solid draft of the human genome will allow researchers to characterize genotypes to ever-finer degrees of detail, and to continue to identify genetic traits associated with disease in individuals and families. However, much of the genetic variation that is associated with cancer seems to modify risk only in the presence of environmental variability, both for exposures that increase, and those that decrease, risk. There are 10to 200-fold differences in rates of disease across different geographic locations around the world and, over 50 years, up to 10-fold differences when comparing the same geographic location over time. These cannot be explained by differences in genes, but only by differences in exposures, modified by the interaction between genetic variation and such exposures.