Associations of mutation profiles with clinical outcomes among metastatic colorectal cancer patients at the United States-Mexico border.

Abstract

e15519 Background: The incidence of CRC among Hispanics living in the USA varies according to their country of origin, supports the idea that differences in ancestry may contribute to the differences in the incidence of CRC. Moreover, Hispanics-Latino(HL) patients usually present with a more advanced stage and have a higher mortality rate compared to other ethnic cohorts. Although it is unknown, the incidence of CRC has been substantially increasing among younger Hispanics. We sought to characterize the tumor mutation profile of mCRC patients and associate with clinical outcomes among Hispanic population. Methods: We retrospectively collected the data from next generation sequencing of 49 patients with metastatic CRC (treated at TTUHSC from 2012 to 2020. We identified the most frequent alterations in our study sample and associated with the clinical outcomes. Association analyses were performed using chi square test, unpaired t-test, log rank test and the Cox proportional hazards regressions. Results: Of 49 patients with mCRC, the average age of patients at the time of diagnosis was 57 years with 98% Hispanic, and 32(65%) male. Most of the patients had stage IV disease (98%) and left side CRC (31, 67%). In our study cohort, the most commonly mutated genes identified as APC (37/11, 77.08%), TP53 (29/19, 60.42%), KRAS (23/25, 47.92%), NOTCH 12/36 (25.00%), BRCA 1&2 11/37 (22.92%) and FLT1 11/37 (22.92%). None of the identified mutations were found to be associated with overall survival. However, the presence of the FLT1 mutation was associated with a reduced risk of progression to additional chemotherapy (P=0.031). Compared to the left side CRC, the BRCA mutation appeared slightly higher on the right side of the CRC (p=0.057). In compare to data from larger national and international colon cancer databases ( COSMIC and METABRICS); HL patients showed a significantly higher proportion of frequent mutations. Compared to other ethnic cohorts, HL patients were relatively younger (57 vs. 63 years) and the male to female ratio was observed to be remarkably higher as well (1.77:1 vs. 1.32:1). In our study, the combination of mutations (TP53, APC, and KRAS) was associated with worse clinical outcomes. Our study demonstrated that worse clinical outcomes were correlated with. Conclusions: Our study is the first to characterize the most common genetic alterations among HL patients with mCRC. The most frequent identified mutations including TP53, APC, KRAS, NOTCH, and BRCA were even higher in HL cohort than the national and international databases ( COSMIC and METABRICS). Our data support the motion that molecular drivers of colon cancer might be different in HL patients.