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


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.

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Fig. 1: Genetic ancestry analysis.
Fig. 2: MSI-target gene analyses.

Data availability

Data supporting the results reported in this manuscript can be found within the article and its Supplementary Files.


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The authors acknowledge Dr. Adriane Feijó and Dr. Luciane Sussuchi for their assistance in preparing the figures.


This study was partially supported by Barretos Cancer Hospital Internal Research Funds (PAIP) of participant authors and the Public Ministry of Labor – Campinas, São Paulo (Research, Prevention, and Education of Occupational Cancer). RMR was the recipient of a National Council of Technological and Scientific Development (CNPq) scholarship. AMC had financial support from the São Paulo Government (São Paulo Research Foundation – FAPESP) through the grants numbers 2019/21722–0 and 2018/22097–0.

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GNB participated in study design, collection of the data, analyzed the data, and prepared the manuscript. RD participated in the collection of the clinical data and analyzed the data. AMC participated in the collection of the data and analyzed the data. AB participated in re-evaluation of the clinical data and analyzed the data. MO participated in the statistical analyses and analyzed the data. RP participated in the ancestry analyses and analyzed the data. CS-N participated in the collection of the data and re-evaluation of the diagnoses. DPG participated in re-evaluation of the diagnoses and analyzed the data. RMR participated in study design, coordination, analyses of the data, and prepared the manuscript. All authors read and approved the final manuscript.

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Correspondence to Rui Manuel Reis.

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The study was evaluated and approved by Institutional Ethics Committee (protocol number: 600/2012 - CAAE: 02468812.30000.5437).

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Berardinelli, G.N., Durães, R., Mafra da Costa, A. et al. Association of microsatellite instability (MSI) status with the 5-year outcome and genetic ancestry in a large Brazilian cohort of colorectal cancer. Eur J Hum Genet 30, 824–832 (2022).

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