Association between KRAS mutation and alcohol consumption in Brazilian patients with colorectal cancer

Abstract

Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Detection before metastasis and efficient treatment of disease significantly improve patient survival and quality of life. However, limitations in diagnosis and postoperative surveillance are associated with low CRC detection and survival rates. Thus, this project aimed to evaluate the molecular profile of patients diagnosed with CRC, as molecular biomarkers constitute a new frontier for diagnosis, treatment and prognosis. Methods and Results: 42 patients were included in the study, predominantly male (59.5%), with a median age of 63 years (SD: 10.0; min: 41; max: 83). The majority of primary tumors were located in the rectum (38.1%), in the sigmoid (33.3%) and in the ascending (21.4%) colon. We evaluated the genes KRAS, NRAS, BRAF, EGFR and TP53 using Sanger sequencing. Somatic and germline mutations were found in the KRAS, EGFR and TP53 genes, with the most common somatic alteration being rs121913529 in KRAS. This variant was also strongly associated with alcoholism (p = 0.002). Furthermore, patients with somatic mutations in TP53 had significantly higher mortality compared to those with wild-type alleles (OR: 11.2; 95% CI 1.25–2.45). Conclusions: Our findings support a relationship between alcohol consumption and the rs121913529 mutation, which is classified as pathogenic for colorectal cancer. Thus, further studies investigating the link between alcohol consumption, colorectal carcinogenesis and tumor progression ought to be conducted.