KRAS Oncogenic Mutation Pattern in Pakistani Patients Presenting with Colorectal Adenocarcinoma in a Northern Tertiary Referal Centre

Abstract

Veterinary Pathology Pathology Abstract Colorectal cancer is a global disease with marked morbidity and mortality. Involvement of genetic and environmental factors produces variability in its prevalence. KRAS (Kirsten rat sarcoma viral oncogene homologue) is one of the important genes responsible for sporadic CRC. The constitutive GTPase activity of the gene is lost when it gets mutated and so the deregulated cells undergo unrestricted proliferation leading to oncogenesis. From therapeutic point of view, patients with KRAS mutations do not benefit from epidermal growth factor receptor inhibition drugs as those who possess normal KRAS. The analysis of KRAS mutations is therefore important from both diagnostic as well as therapeutic purposes. Diagnostic methodology and the valuable information of this study will be quite helpful in future. The objectives of this study were to document the KRAS oncogenic mutation pattern mostly in Northern Pakistani residents presenting in AFIP, Rawalpindi after their intestinal resection due to CRC. The other objective was to relate this mutation pattern with histopathological categorical variables like age, gender, presenting clinical complaint, tumor site, size, histological differentiation, modified Duke Stage of tumor, nodal metastasis and metastasis in other organs. Hundred and eighty one cases of CRC from persons residing in northern area of Pakistan were collected and observed for the above mentioned parameters. DNA was extracted from the tumors and normal tissues of all the study subjects. PCR was done for gene amplification and the status of KRAS mutations in Pakistani CRC patients was analyzed by gene sequencing. The results showed more prevalence of CRC in the males of northern areas of Pakistan. Both males and females with higher average age had high tendency to acquire CRC. Rectum was found to be the most common location of CRC, followed by sigmoid. Exophytic well differentiated adenocarcinomas were the most common form of CRC. Gene sequencing did not show even a single KRAS mutation in the tested samples. It can be inferred from this study that either there is no KRAS mutation in northern area patients suffering from CRC or the mutation frequency of this particular gene is relatively very low as compared to the results of studies reported in the literature. A wider scale study of these patients may prove the cause of CRC to be due to mutation of some other genes or may be due to some non-genetic factors.