Pan-Cancer Analyses Reveal Disparities in Tumor Genomic Profiles by Race/Ethnicity, Age, and Sex

Abstract Background: We aimed to investigate racial/ethnic, age of onset, and sex disparities in tumor genomic profiles across 34 solid cancer types. Methods: We analyzed tumor genomic and clinical data from 104,399 patients with 34 solid cancer types from the Genomics Evidence Neoplasia Information Exchange consortium (2011–2023). Patients were classified by race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, Asian or Pacific Islander, and other/unknown), age at onset (<50, 50–69, ≥70 years), and sex. We assessed the prevalence and spectrum of somatic mutations and compared tumor mutational burden (TMB) across groups using adjusted regression models. Results: Significant racial/ethnic and age of onset differences in TMB were observed in 15 and 21 cancer types, respectively. Males had higher TMB in non–small cell lung cancer, melanoma, hepatobiliary cancer, nonmelanoma skin cancer, and germ cell cancers, whereas females had higher TMB in colorectal, glioma, and head and neck cancers. Notable racial/ethnic disparities were found in frequently mutated genes. Compared with non-Hispanic White patients, Asian or Pacific Islander [OR = 0.23 (95% confidence interval, 0.19–0.29)] and Hispanic [0.56 (0.44–0.71)] patients had lower frequencies of KRAS mutations in non–small cell lung cancer, whereas non-Hispanic Black patients had higher frequencies of KRAS in colorectal cancer [1.61 (1.37–1.90)], TP53 in breast cancer [1.77 (1.51–2.07)], and endometrial cancer [2.28 (1.66–3.12)]. Older patients generally had more mutated genes although some genes in seven cancer types showed higher frequencies in patients below 50. Conclusions: Distinct spectrums of somatic mutations exist across various racial/ethnic, age of onset, and sex groups. Impact: This study presents a pan-cancer assessment of disparities in tumor genomic profiles and can enhance our understanding of disparities in cancer etiology and prognosis.