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

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.