Using Tumor Mutational Profiles to Infer Etiologic Heterogeneity of Cancers

• Activity Number: 501
• Type: Invited
• Date/Time: Wednesday, August 7, 2013 : 10:30 AM to 12:20 PM
• Sponsor: General Methodology
• Author(s): Colin B. Begg*+
• Companies: Memorial Sloan-Kettering Cancer Center
• Keywords: etiologic heterogeneity ; cancer risk ; epidemiology

Abstract

Cancer has traditionally been studied using the disease site of origin as the organizing framework. Recent advances in molecular genetics have begun to challenge this taxonomy, as detailed molecular profiling of tumors has led to discoveries of subsets of tumors that possess distinct clinical and biological characteristics. This is increasingly leading to research investigating whether these sub-types have distinct etiologies. Research in this field has typically involved the comparison of individual risk factors between tumors classified on the basis of candidate tumor characteristics. In this talk a more general, conceptual methodologic framework is presented, with a view to providing formal strategies for designing and analyzing epidemiologic studies to investigate etiologic heterogeneity. It will be shown that classifications with larger etiologic heterogeneities inevitably possess greater disease risk predictability overall, and that studies of double primary malignancies are uniquely informative for investigating this topic. The strategy paves the way for a structured approach to investigating the relationship between germ-line and somatic mutational profiles.