Exploring genetic susceptibility to cancer in diverse populations.
Incidence rates for many cancers differ markedly by race/ethnicity and furthering our understanding of the genetic and environmental causes of such disparities is a scientific and public health need. Genome-wide association studies (GWAS) are widely acknowledged to provide important information about the etiology of common cancers. To date, these studies have been primarily conducted in European-derived populations. There are important reasons for extending the reach of GWAS studies to other groups and for conducting multiethnic genetic studies involving multiple populations and admixed populations. These include a (1) need to discover the full scope of variants that affect risk of disease in all populations, (2) furthering the understanding of disease pathways, and (3) to assist in fine-mapping of genetic associations by exploiting the differences in linkage disequilibrium between populations to narrow the range of marker alleles demarking regions that contain a true biologically relevant variant. Challenges to multiethnic studies relating to study power, control for hidden population structure, imputation, and use of shared controls for multiple cancer endpoints are discussed.
Haiman
Christopher A
CA
Department of Preventive Medicine, Keck School of Medicine and the Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA. haiman@usc.edu
Stram
Daniel O
DO
D005006:Ethnicity / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011634:Public Health / Q000379:methods; D012307:Risk Factors