Abstract Background: We aimed to investigate racial/ethnic, age-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 GENIE Consortium (2011-2023). Patients were classified by race/ethnicity (non-Hispanic White NHW, non-Hispanic Black NHB, Hispanic, Asian or Pacific Islander API, 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-onset differences in TMB were observed in 15 and 21 cancer types. Males had higher TMB in non-small cell lung cancer (NSCLC), melanoma, hepatobiliary, non-melanoma skin, and germ cell cancers, while females had higher TMB in colorectal, glioma, and head & neck cancer. Notable racial/ethnic disparities were found in frequently mutated genes. Compared with NHW, API OR=0.23 (95%CI=0.19-0.29) and Hispanic 0.56 (0.44-0.71) patients had lower frequencies of KRAS mutations in NSCLC, while NHB 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 under 50. Conclusion: Distinct spectrums of somatic mutations exist across various racial/ethnic, age-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.
Wen et al. (Thu,) studied this question.