Association of microsatellite instability (MSI) status with the 5-year outcome and genetic ancestry in a large Brazilian cohort of colorectal cancer

Author(s)

Berardinelli, Gustavo Noriz ; Duraes, Ronilson ; da Costa, Allini Mafra ; Bragagnoli, Arinilda ; de Oliveira, Marco Antonio ; Pereira, Rui ; Scapulatempo-Neto, Cristovam ; Guimaraes, Denise Peixoto ; Reis, Rui Manuel

• Document type: Journal article
• Source: European Journal of Human Genetics; v. N/A, p. 9-pg., 2022-04-26.

Abstract

Colorectal cancer (CRC) has a high incidence and mortality worldwide. Microsatellite instability (MSI) is crucial in CRC, with distinct molecular and clinicopathological features in patients. Nowadays, it is a predictive marker for immunotherapy. We proposed to evaluate the 5-year outcome of MSI status in 1002 Brazilian CRC, and associate it with genetic ancestry, molecular and clinicopathological features. MSI evaluation was performed using molecular markers. MSI+ tumors were analyzed for alterations in 23 MSI-targeted genes. Genetic ancestry was evaluated using an Ancestry-Informative markers panel. MSI status was analyzed in relation to CRC specific survival and other clinical and genetic variables. MSI+ status was observed in 10.5% of cases. MSI+ status was significantly associated with the anatomic site right colon, mucinous histological type, clinical stage II, histological grade III/undifferentiated, no recurrence of disease, and live cases without cancer. No association of MSI status with genetic ancestry components was observed. MSI-targeted genes analyses showed the most frequently altered genes: ATM, EGFR, MRE11, ROCK1, and TGFBRII. There was a statistically significant difference in cancer-specific survival between cases according to MSI status. This study constitutes the most comprehensive analyses of the MSI impact on the Brazilian CRC. MSI+ frequency in Brazilian CRC agreed with the literature and was associated with several clinicopathological features related with less aggressive tumors, independently of their genetic ancestry. (AU)

• FAPESP's process: 18/22097-0 - Malignant neoplasms of the 18 cities of Barretos Regional Health District (RhD), Sao Paulo, Brazil: the importance of a population-based cancer registry
• Grantee: Allini Mafra da Costa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/21722-0 - Cancer survival on the northwest of São Paulo state, Brazil: a regional population-based study
• Grantee: Allini Mafra da Costa
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor