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Open Access Research article

KRAS mutations: variable incidences in a Brazilian cohort of 8,234 metastatic colorectal cancer patients

Carlos Gil Ferreira123*, Veronica Aran2, Ilana Zalcberg-Renault13, Ana Paula Victorino24, Jonas H Salem4, Martin H Bonamino13, Fernando M Vieira24 and Mariano Zalis1

Author Affiliations

1 Progenética Diagnósticos Moleculares, Av. Presidente Vargas, 962 3 Andar, Cep: 20071-002 Rio de Janeiro, RJ, Brazil

2 Brazilian National Cancer Institute (INCA); Coordenação de Pesquisa Clínica e Incorporação Tecnológica, Rio de Janeiro, Brazil

3 Divisão de Medicina Experimental, Brazilian National Cancer Institute (INCA), Rio de Janeiro, Brazil

4 Instituto COI de Educação e Pesquisa, Rio de Janeiro, Brazil

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BMC Gastroenterology 2014, 14:73  doi:10.1186/1471-230X-14-73

Published: 10 April 2014

Abstract

Background

KRAS mutations are frequently found in colorectal cancer (CRC) indicating the importance of its genotyping in the study of the molecular mechanisms behind this disease. Although major advances have occurred over the past decade, there are still important gaps in our understanding of CRC carcinogenesis, particularly whether sex-linked factors play any role.

Methods

The profile of KRAS mutations in the Brazilian population was analyzed by conducting direct sequencing of KRAS codons 12 and 13 belonging to 8,234 metastatic CRC patient samples. DNA was extracted from paraffin-embedded tissue, exon 1 was amplified by PCR and submitted to direct sequencing. The data obtained was analysed comparing different geographical regions, gender and age.

Results

The median age was 59 years and the overall percentage of wild-type and mutated KRAS was 62.8% and 31.9%, respectively. Interestingly, different percentages of mutated KRAS patients were observed between male and female patients (32.5% versus 34.8%, respectively; p = 0.03). KRAS Gly12Asp mutation was the most prevalent for both genders and for most regions, with the exception of the North where Gly12Val was the most frequent mutation found.

Conclusions

To the best of our knowledge this is one of the largest cohorts of KRAS genotyping in CRC patients and the largest to indicate a higher incidence of KRAS mutation in females compared to males in Brazil. Nevertheless, further research is required to better address the impact of gender differences in colorectal cancer.

Keywords:
KRAS; Mutation; Gender; Cohort; Colorectal cancer