Racial/Ethnic Disparities in Genomic Sequencing

Abstract

Importance Although poorly understood, there is heterogeneity in the molecular biology of cancer across race and ethnicities. The representation of racial minorities in large genomic sequencing efforts is unclear, and could have an impact on health care disparities. Objective To determine the racial distribution among samples sequenced within The Cancer Genome Atlas (TCGA) and the deficit of samples needed to detect moderately common mutational frequencies in racial minorities. Design, Setting, and Participants This was a retrospective review of individual patient data from TCGA data portal accessed in July 2015. TCGA comprises samples from a wide array of institutions primarily across the United States. Samples from 10 of the 31 currently available tumor types were analyzed, comprising 5729 samples from the approximately 11 000 available. Main Outcomes and Measures Using the estimated median somatic mutational frequency, the samples needed beyond TCGA to detect a 10% and 5% mutational frequency over the background somatic mutation frequency were calculated for each tumor type by racial ethnicity. Results Of the 5729 samples, 77% (n = 4389) were white, 12% (n = 660) were black, 3% (n = 173) were Asian, 3% (n = 149) were Hispanic, and less than 0.5% combined were from patients of Native Hawaiian, Pacific Islander, Alaskan Native, or American Indian decent. This overrepresents white patients compared with the US population and underrepresents primarily Asian and Hispanic patients. With a somatic mutational frequency of 0.7 (prostate cancer) to 9.9 (lung squamous cell cancer), all tumor types from white patients contained enough samples to detect a 10% mutational frequency. This is in contrast to all other racial ethnicities, for which group-specific mutations with 10% frequency would be detectable only for black patients with breast cancer. Group-specific mutations with 5% frequency would be undetectable in any racial minority, but detectable in white patients for all cancer types except lung (adenocarcinoma and squamous cell carcinoma) and colon cancer. Conclusions and Relevance It is probable, but poorly understood, that ethnic diversity is related to the pathogenesis of cancer, and may have an impact on the generalizability of findings from TCGA to racial minorities. Despite the important benefits that continue to be gained from genomic sequencing, dedicated efforts are needed to avoid widening the already pervasive gap in health care disparities.

Integrated Analysis of Genetic Ancestry and Genomic Alterations across Cancers

“…For example, higher incidence or mortality rates from stomach, liver, and thyroid cancers are reported in Asian American patients; correspondingly, greater numbers of EAA samples were collected in the TCGA specimens for these cancer types. Taken together, although the sample sizes of racial minorities in TCGA may still not be sufficient for de novo identification of racial group-specific genomic alterations at a cancer type-specific level (Huang et al, 2017; Spratt et al, 2016), TCGA provides one of the largest sample cohorts across most common adult cancer types, with comprehensive clinical information and multidimensional genomic profiles for studies of the effects of genetic ancestry on genomic alterations. Using the same computational approaches, we also estimated global and local genetic ancestry for 1,251 cancer cell lines, derived from 29 primary sites (Table S4), whose SNP array genotyping data were retrieved from the Cancer Cell Line Encyclopedia and the Genomics of Drug Sensitivity in Cancer.…”

Exome Sequencing of African-American Prostate Cancer Reveals Loss-of-Function ERF Mutations

“…The notion that somatic genetic factors may influence tumor biology differentially across distinct ancestral backgrounds is exemplified by high EGFR mutation rates in patients of Asian ancestry with non-small cell lung adenocarcinoma (up to 50% of patients), compared to patients of European ancestry (10–15% of cases) (7). Large-scale genomic characterization studies are predominated by tumor samples from patients of European ancestry (8). While of immense value, the limited racial and ethnic diversity of these studies may preclude the detection of genomic events and patterns that are unique or enriched in underrepresented groups.…”

Somatic Mutations and Ancestry Markers in Hispanic Lung Cancer Patients

“…1 However, H/Ls represent only 3% of patients characterized in the Cancer Genome Atlas and Indigenous Americans represent less than 0.5%. 2 Since precision medicine is driven by data that primarily represents non-Hispanic white (NHW) patients, there is a significant potential health disparity for under-represented groups. 3–6 Non-small cell lung cancer (NSCLC), is the leading cause of cancer death among H/L men and second only to breast cancer in H/L women.…”