Abstract C043: Ethnic disparities among pancreatic cancer patients undergoing germline testing

Abstract

Background: New NCCN guidelines recommend germline testing for all patients with confirmed pancreatic cancer (PC) regardless of stage, family history, or ethnicity. PC is linked to inherited cancer susceptibility syndromes, with approximately 10% of cases occurring in the presence of family history. Per SEER statistics, African-Americans (AA) have the highest incidence rate (67% higher) of PC of all ethnic groups and the worse prognosis. Current data links this risk to social and access issues rather than biology. We aim to determine whether the prevalence of germline mutations associated with increased PC susceptibility varies by ethnicity. Methods: We retrospectively examined publicly-available, de-identified, germline and clinical data of patients with a diagnosis of pancreatic cancer (PC) referred to Color Genomics by a healthcare provider for testing of 30 genes associated with hereditary cancer risk. Clinical data included age at diagnosis, sex, self-reported ethnicity, family history of cancer, and personal history of cancer. Ashkenazi Jewish (AJ) ancestry was classified as an ethnic group. Germline genetic variants were classified as pathogenic (P), likely pathogenic (LP), variant of uncertain significance (VUS), likely benign, or benign. Prevalence of P/LP and VUS variants was compared among subgroups classified by age at diagnosis (£ 65 or > 65 years-old), sex, self-reported ethnicity, family history of PC, and personal history of other cancer using chi-square tests. Results: We identified 167 patients with PC of any stage who underwent germline testing. Among these, 47.9% were female and 52.1% male. Ethnic composition was 73.1% Caucasian, 8.4% AJ, 3.6% Hispanic, 3.6% AA, 4.2% Asian, and 7.2% of other or unknown ethnicity. Twenty-four (14.4%) patients carried a P/LP variant, and 45 (26.9%) patients carried a VUS. The most prevalent P/LP variants were BRCA2 (29.6%), ATM (22.2%), and MUTYH (14.8%). APC (18.4%), BRCA2 (14.3%), and ATM (12.2%) were the most prevalent VUS variants. AJ patients had an increased prevalence of P/LP BRCA2 variants (83%, n=5). Ethnicity was significantly associated with risk of carrying any P/LP variant (p = 0.049) but not with a VUS; this association was lost when excluding those of AJ ancestry. Age, sex, family history of PC, and personal history of a second cancer were not associated with risk of carrying any P/LP or VUS variants. Conclusions: Germline mutations are prevalent among PC patients and highest among those of AJ ancestry. Although the prevalence of germline variants is not associated with other ethnic groups, our study highlights the underrepresentation of minorities in germline testing databases, particularly AA. The prevalence of germline variants in minority ethnic groups with PC remains an understudied area and is an example of how barriers to access can limit our understanding of diseases. Further studies are needed to address this critical unmet need. Citation Format: Ana I Velazquez, Carolina Bernabe Ramirez, Daniel H Kwon, Ryan Leibrandt, Narjust Duma. Ethnic disparities among pancreatic cancer patients undergoing germline testing [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C043.

A systematic review and meta-analysis of germline BRCA mutations in pancreatic cancer patients identifies global and racial disparities in access to genetic testing

“… 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 For BRCA1 and BRCA2 genes, founder mutations have been identified across multiple ethnicities, 67 , 68 including African Americans and Hispanics, only seldom profiled in PC due to global and racial disparities in BRCA testing uptake. 26 , 27 This will likely compound the already existing inequities in cancer care described for patients with PC, 23 , 24 , 25 which translates to poorer survival amongst non-white populations, especially African Americans. 26 , 28 , 29 , 30 Multi-level interventions are encouraged to enhance inclusion of multiple ethnicities in PC genomic studies to better understand cancer susceptibility across diverse populations and improve tailored early detection strategies, to allow minority groups access to innovative targeted treatments and, more in general, to mitigate health disparities in cancer screening and treatment.…”

“…[18][19][20][21][22] This is a major public health concern as it precludes access to innovative and potentially active oncological treatments, limits scientific progress by underappreciating genetic diversity, and translates into significant health disparities of already marginalized racial minorities. [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] Studies of ethnic and geographic variability of gBRCA testing uptake and gBRCAm prevalence in PC are currently lacking. To the best of our knowledge, this aspect has only been described in the phase III POLO trial of maintenance olaparib in patients with advanced, platinum-sensitive PC carrying a gBRCAm.…”

“… 18 , 19 , 20 , 21 , 22 This is a major public health concern as it precludes access to innovative and potentially active oncological treatments, limits scientific progress by underappreciating genetic diversity, and translates into significant health disparities of already marginalized racial minorities. 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 …”