Integrative epidemiology: from risk assessment to outcome prediction.

In this paper, we advance the concept of integrative epidemiology. Our unifying premise is that the same genes that are implicated in cancer risk may also be involved in a person's propensity to carcinogenic exposure and/or to modulation of therapeutic outcome. In the coming years, molecular epidemiology will play an increasingly prominent role in early detection of cancer and in identifying genetically high-risk subgroups that might benefit disproportionately from more intensive screening or chemoprevention interventions. Molecular epidemiology is also integral to pharmacogenetic research, by constructing genetic profiles that could be used to individualize therapy and to understand the functional consequences of chemoprevention, chemotherapy, or radiotherapy response. At the level of risk assessment, the focus might be on germline polymorphisms in candidate genes; for early detection, epigenetic events in these same or other genes may be relevant; and tumor tissue expression levels, loss of heterozygosity, genomic amplification, rearrangements, or somatic mutations in the same classes of genes may determine outcome. We will provide examples of how changes in the function of a single gene can contribute to susceptibility to carcinogenic exposure, predisposition to cancer development, patient prognosis, and prediction of outcome.