Methodologic perspectives on the study of multiple primary cancers

Investigations of the patterns of occurrence of multiple primary cancers of the same organ or of different organs provide important data concerning the carcinogenic potential of various therapies used in the treatment of cancer. Associations between cancers arising in different organs may also suggest hypotheses concerning shared risk factors that are strongly related to the incidence of both types of tumors. Studies of multiple primaries of a single organ permit exploration of a number of questions of etiologic interest. First, a strong same-site association over and above what would be expected on the basis of known risk factors suggests that the unexplained proportion of cancer incidence represents relatively stable characteristics of individuals rather than sporadic events. Second, detailed comparisons of risk factors for first versus second primaries of a particular site may help to identify etiologically distinct subtypes of the disease. Third, even if distinct subtypes do not exist, the study of risk factors for a second primary among those who have had a first primary of the same site may enhance the detection of the etiologic role of a particular exposure. Such detection is enhanced when the effects of the exposure are modified by some other factor that is itself a strong risk factor but that is not measured. Finally, studies of multiple primaries of a single site are of particular benefit to clinicians who must decide on appropriate levels of surveillance and preventive intervention.