Racial Disparities in Lung Adenocarcinoma: The Contribution of African Ancestry

It is well-known that racial disparities exist in lung cancer, with disproportionally higher incidence of lung cancer in African Americans. Moreover, emerging evidence indicates racial differences in genomic profiles, which might influence incidence of subsequent somatic alterations. Therefore, a global ancestry analysis was performed using The Cancer Genome Atlas database to assess genetic alterations in patients with lung adenocarcinomas with African ancestry; findings of this study are summarized here.

Since a substantial proportion of the US population consists of genetically admixed populations, the study sought to quantitatively determine the ancestral composition for each patient using The Cancer Genome Ancestry Atlas and LAMP data sets, which contained 518 samples, including 393 self-reported whites and 52 African Americans. The ancestral composition in terms of the proportion of European, African, East Asian, and native American ancestry was estimated; the dominant ancestry was defined as ≥50% of admixture from one reference population.

The global ancestry analysis identified 50 African ancestry cases, with mean ancestry of 80.3%. The dominant African ancestry group matched the self-reported race with 96% accuracy. A total of 9 subjects were identified to have ≥90% African ancestry, 22 subjects with 80% to 90% African ancestry, 12 subjects with 70% to 80% African ancestry, and 7 subjects with 50% to 70% African ancestry. In the ≥90% African ancestry subgroup, a higher proportion of alterations in TP53, KRAS, STK11, RB1, CACNA1S, and JAK2 were identified compared with the lower African ancestry subgroups. In terms of genetic alterations identified, mutations in the TP53 gene were found to occur most frequently in the African ancestry population.

Outcomes were significantly worse for patients with increasing African ancestry in terms of overall survival and progression-free survival. Median overall survival was 14.5 months for patients with ≥90% African ancestry compared with 71.47 months for patients with 70% to 80% African ancestry (P = .048); median progression-free survival was 12.8 months for patients with ≥90% African ancestry compared with 33.5 months for patients with 80% to 90% African ancestry, and 47.1 months for those with 70% to 80% African ancestry (P = .002).

These results confirm that African ancestry is associated with worse survival outcomes among patients with lung adenocarcinoma, with higher African composition proportionally associated with worse survival and higher mutational load.

Source: Lee M, et al. J Clin Oncol. 2001;39(suppl 15):Abstract 8516.