The search for cancer risk factors: When can we stop looking?

In recent decades, countless cohort, case-control, and ecologic studies hav e been conducted in the search for cancer risk factors. On the basis of kno wledge gained from these studies. various influential commentaries have end eavored to classify the extent to which the total cancer burden is attribut able to general categories of risk, such as diet, tobacco, sun exposure, an d others. These commentaries have led to the conventional wisdom that most of the cancer burden is caused by environmental factors and relatively litt le is directly attributable to genetic susceptibility. In the face of the apparent knowledge that the cancer burden is essentially fully "explainable" on the basis of known environmental risks. this articl e addresses the conceptual and empirical basis of the continued search for new risk factors, It proposes that the extent of the aggregation of cancer within individuals in the population-that is, the occurrence of second prim ary cancers-is a crucial statistic in this context. A study of the incidenc e of second primary melanoma suggests that the bulk of the risk variation i n this disease cannot be explained by known risk factors. The implications of these ideas for research strategy and for public health policy are discu ssed.