Association between tumor mutation profile and clinical outcomes among Hispanic-Latino patients with metastatic colorectal cancer.

Abstract

17 Background: According to the World Health Organization GLOBOCAN database, in 2019, approximately 1.8 million new colorectal cancer cases were diagnosed, and almost 861,000 deaths were reported. In the United States, CRC is the third most frequent type of cancer and the second leading cause of cancer-related death. Although the overall incidence of CRC among the Hispanic population has been declining over the last decades, recently, a dramatic increase in CRC incidents among Hispanics younger than 50 years of age (early-onset CRC) has been reported. The increase in the incidence of early-onset CRC is markedly more significant in Hispanic-Latino (HL) patients population (45%) than in non-Hispanic Whites (NHW) (27%) and African-Americans (AA) (15%). Additionally, in contrast to NHW, Hispanics have a worse survival rate. The exact reason for these racial disparities and the biology of CRC in the HL population are not well understood. Therefore, we performed this study to better understand the biology of the disease in HL patients, which might help to identify new directions for targeted therapy. Methods: For the study, 52 formalin-fixed paraffin-embedded (FFPE) tumor tissue samples were collected and analyzed. We compared the results with individual patient clinical histories and outcomes. Of 52 patients with mCRC, 52 (100%) were identified as HL. We identified several commonly altered genes in HL patients ( APC, TP53, KRAS, GNAS, PICK3CA, and NOTCH). Compared to those in other studies. Results: Mutation frequencies in the APC gene were significantly higher among HL patients with mCRC. Moreover, the prevalence of the APC mutation was significantly higher among male HL patients compared to female patients. The combination of mutations in the APC, NOTCH, and KRAS genes in the same tumors was associated with a higher risk of progression after the first-line of chemotherapy and worse overall survival. In addition, mutations in the combination of GNAS and AURKA genes were associated with a significantly higher risk of progression after the first-line of chemotherapy. Conclusions: The data support the notion that the molecular drivers of colon cancer might be different in HL patients compared to other racial/ethnic groups.