Abstract C043: Ethnic disparities among pancreatic cancer patients undergoing germline testing
Authors: Velazquez Ana I , Ramirez Carolina Bernabe , Kwon Daniel H , Leibrandt Ryan , Duma Narjust 
Published: September 2020

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 &gt; 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.