Cancer Genomics: Diversity and Disparity Across Ethnicity and Geography.

Ethnic and geographic differences in cancer incidence, prognosis, and treatment outcomes can be attributed to diversity in the inherited (germline) and somatic genome. Although international large-scale sequencing efforts are beginning to unravel the genomic underpinnings of cancer traits, much remains to be known about the underlying mechanisms and determinants of genomic diversity. Carcinogenesis is a dynamic, complex phenomenon representing the interplay between genetic and environmental factors that results in divergent phenotypes across ethnicities and geography. For example, compared with whites, there is a higher incidence of prostate cancer among Africans and African Americans, and the disease is generally more aggressive and fatal. Genome-wide association studies have identified germline susceptibility loci that may account for differences between the African and non-African patients, but the lack of availability of appropriate cohorts for replication studies and the incomplete understanding of genomic architecture across populations pose major limitations. We further discuss the transformative potential of routine diagnostic evaluation for actionable somatic alterations, using lung cancer as an example, highlighting implications of population disparities, current hurdles in implementation, and the far-reaching potential of clinical genomics in enhancing cancer prevention, diagnosis, and treatment. As we enter the era of precision cancer medicine, a concerted multinational effort is key to addressing population and genomic diversity as well as overcoming barriers and geographical disparities in research and health care delivery.