Exploring genetic susceptibility to cancer in diverse populations

Abstract

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.

Figure 1

Multiple risk regions for prostate cancer identified in a multiethnic sample. Figure adapted from Haiman et al. [19]. A) The location of an ancestry signal at 8q24 from an admixture-based genome-wide scan conducted in African American men. B) Fine-mapping of the putative 8q24 risk locus in prostate cancer cases and controls from five racial/ethnic populations. P-values for each SNP highlight multiple regions harboring common risk alleles for prostate cancer that are defined by independent and highly statistically significant associations.