title: Cancer heterogeneity: origins and implications for genetic association studies.
abstract: Genetic association studies have become standard approaches to characterize the genetic and epigenetic variability associated with cancer development, including predispositions and mutations. However, the bewildering genetic and phenotypic heterogeneity inherent in cancer both magnifies the conceptual and methodological problems associated with these approaches and renders difficult the translation of available genetic information into a knowledge that is both biologically sound and clinically relevant. Here, we elaborate on the underlying causes of this complexity, illustrate why it represents a challenge for genetic association studies, and briefly discuss how it can be reconciled with the ultimate goals of identifying targetable disease pathways and successfully treating individual patients.
authors.affiliation: Institute for Quantitative Biomedical Sciences, The Geisel School of Medicine, Dartmouth College, One Medical Center Drive, Lebanon, NH 03756, USA.
authors.forename: Davnah
authors.initials: D
authors.lastname: Urbach
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lupien
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Karagas
authors.forename: Jason H
authors.initials: JH
authors.lastname: Moore
mesh_terms: D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D010641:Phenotype