Abstract B060: Hereditary cancer testing across race and ethnicity: Differences in patient characteristics and genetic test results
Authors: Krinshpun Shifra , Mitchell Breeana L. , Zhang Jingwen , Sun Nicholas , Bristow Sara L. , Tin Antony , Liu Minetta C. , ElNaggar Adam , Aleshin Alexey , Weitzel Jeffrey N. 
Published: December 2023

Rates of pathogenic/likely pathogenic variants (PGVs) and variants of uncertain significance (VUS) in genes associated with hereditary cancer syndromes vary across race and ethnicity. Here, we report on differences in physician orders and test results across race and ethnicity in patients referred for hereditary cancer testing at a single laboratory in the United States.  Patients (N=109,264) with self-reported Ashkenazi Jewish (AJ; N=2,788), Black (N=19,538), East Asian (E Asian; N=1,953), Hispanic (N=19,920), South East Asian (SE Asian; N=845), South Asian (S Asian, N=626), and White (N=63,594) ethnicities who had hereditary cancer testing between 2020 and 2022 were included. Patient characteristics were summarized and genetic test results were compared  (Chi-Square test, White as the reference group). Across all races and ethnicities, most patients were female (94-96%) and reported a family history of cancer (88-96%), while 29%-32% reported a personal history of cancer. Mean age at testing varied across groups (AJ 48.4±15.5 years, Black 43.4±13.5 years, E Asian 45.1±12.8 years, Hispanic 42.8±13.2 years, SE Asian 45.2±13.2 years, S Asian 43.9±14.4 years, White 46.1±14.3 years). The number of genes tested (small panel &lt;20, medium panel 20-53, large panel &gt;53) varied across ethnicities: White (14%, 80%, 5.4%), AJ (8.2%, 86%, 5.6%), Black (14%, 83%, 3.1%), E Asian (9.2%, 88%, 2.4%), Hispanic (15%, 81%, 4.5%), S Asian (15%, 82%, 3.2%), SE Asian (12%, 82%, 5%). Compared to White patients (10%), PGV rates were significantly lower in Black (4.7%, p&lt;0.0001), E Asian (5.2%, p&lt;0.0001), Hispanic (6.5%, p&lt;0.0001), and SE Asian (4.3%, p&lt;0.0001) patients, and significantly higher in AJ patients (15%, p&lt;0.0001). No differences were observed compared with S Asian patients (7.7%, p=0.0522). Across all groups, most patients with PGVs had findings in actionable genes (AJ 96%, Black, 81%, E Asian 92%, Hispanic 88%, S Asian 90%, SE Asian 94%, White 86%). The most common genes with actionable PGVs were BRCA2 (Black, E Asian, SE Asian), CHEK2 (AJ, White), and MUTYH (Hispanic, S Asian).  VUS rates, in the absence of any PGVs, when compared with White patients (20%) were significantly higher in Black (29%, p&lt;0.0001), E Asian (34%, p&lt;0.0001), Hispanic (25%, p&lt;0.0001), S Asian (33%, p&lt;0.0001), and SE Asian (38%, p&lt;0.0001) patients, and were significantly lower in AJ patients (12%, p&lt;0.0001). For all races and ethnicities, the two most common genes with VUS were ATM and APC. In this relatively diverse sample (~36% Hispanic or Black), these data demonstrate that there are variations in hereditary cancer testing with respect to provider ordering patterns (i.e., patient age, panel size) and test results (i.e., PGV rates) across ethnicities. These differences may reflect ancestral PGV patterns, other biologic correlates, or variable application of selection criteria. As previously reported, VUS rates are higher in non-White patients. Improved access to testing and additional evidence generation across all races and ethnicities will help to improve variant curation.

Citation Format: Shifra Krinshpun, Breeana L. Mitchell, Jingwen Zhang, Nicholas Sun, Sara L. Bristow, Antony Tin, Minetta C. Liu, Adam ElNaggar, Alexey Aleshin, Jeffrey N. Weitzel. Hereditary cancer testing across race and ethnicity: Differences in patient characteristics and genetic test results [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B060.