Abstract 4004: Unique patient signatures underlie health disparities in ethnically diverse patients with pancreatic cancer

Abstract

Abstract Introduction: Health disparities in pancreatic cancer (PC) exist but how the underlying biology contributes to this is poorly described. Black Americans have a higher prevalence, present with more advanced disease, and suffer from higher mortality rates than other ethnic groups. Cancer cachexia, or cancer-associated muscle wasting, affects more than 80% of patients with PC. Unique muscular characteristics exist in different ethnic groups which might be contributing to pancreatic cancer health disparities. We hypothesize that Black patients with PC have a distinct muscular profile and are more affected by cancer cachexia than Whites and that unique genomic variations might contribute to this phenomenon in PC tumors between Black and White patients. Methods: Black (including African Americans and Afro-Caribbeans) and non-Hispanic White surgically resected patients with PC between 2010 and 2017 were case matched by age, gender, and tumor grade. Muscular indices were measured from CT scans by dividing the area of the psoas muscles by the L3 vertebral body area to normalize for patient size. Whole-exome sequencing was performed on DNA from tumor and adjacent benign parenchyma. Results: Healthy Blacks have a greater psoas index than Whites (0.8995 vs. 0.6988, p=0.004). When comparing patients with PC, Blacks and Whites were found to have similar psoas indices. Black patients had a greater percent decrease in psoas index than White patients (-25.29% vs. -12.37%, p=0.04). Tumor size inversely correlated to psoas index in Blacks (r=0.4330, p=0.007), but not in Whites (r=0.0025, p=0.9). Similar to tumor size, the positive lymph node ratio (LNR) inversely correlated to psoas index in Black patients (r=0.3930, p=0.01), but not in White patients (r=0.0867, p=0.2). LNR was significantly greater in Whites than Blacks (0.0627 vs. 0.2253, p=0.002), but overall survival was similar in both groups (15.8 vs. 14.3, p=0.7). In whole-exome sequencing, there were 22 mutations, of which several harbored implications in chemoresistance (ABCF1, ANAPC1), metastasis (CYP2A7, CYP21A2), and pathways of tumorigenesis (PHACTR4, PPP1R12B), and had 100% penetrance in Blacks but not in Whites. Seven mutations were present only in tumors of Whites but not Blacks. Conclusion: Black Americans with PC suffer more muscle loss in the early stages of disease than Whites. A decreased psoas index in Black patients is associated with worse prognostic factors. In our genetic analysis, we identified 27 novel mutations not before reported in the literature. We conclude that recognizing biological variance in patients may underlie health disparities and allow investigations toward defining specific targets in a diverse group of patients with PC. Citation Format: Miles E. Cameron, Patrick W. Underwood, Jinping Lai, Jennifer B. Permuth, Andrew R. Judge, Jose G. Trevino. Unique patient signatures underlie health disparities in ethnically diverse patients with pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4004.