title: Implications of genome-wide association studies in cancer therapeutics.
abstract: Genome wide association studies (GWAS) provide an agnostic approach to identifying potential genetic variants associated with disease susceptibility, prognosis of survival and/or predictive of drug response. Although these techniques are costly and interpretation of study results is challenging, they do allow for a more unbiased interrogation of the entire genome, resulting in the discovery of novel genes and understanding of novel biological associations. This review will focus on the implications of GWAS in cancer therapy, in particular germ-line mutations, including findings from major GWAS which have identified predictive genetic loci for clinical outcome and/or toxicity. Lessons and challenges in cancer GWAS are also discussed, including the need for functional analysis and replication, as well as future perspectives for biological and clinical utility. Given the large heterogeneity in response to cancer therapeutics, novel methods of identifying mechanisms and biology of variable drug response and ultimately treatment individualization will be indispensable.
authors.affiliation: UNC Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, NC, 27599-7361, USA.
authors.forename: Jai N
authors.initials: JN
authors.lastname: Patel
authors.forename: Howard L
authors.initials: HL
authors.lastname: McLeod
authors.forename: Federico
authors.initials: F
authors.lastname: Innocenti
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D018095:Germ-Line Mutation; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: association; cancer; genome-wide; polymorphism; replication; therapeutics