Molecular profile of colorectal cancer in Indonesia: is there another pathway?

ABSTRACT

Colorectal cancer is an emerging public health problem in Indonesia and currently ranks among the three highest cancers. Lack of a colonoscopy screening and lifestyle changes might contribute to it. In the last few decades, there is an increasing interest towards the contribution of genetic-environment interaction in colorectal carcinogenesis. Some studies have indicated that CRC might develop through several different pathways; the three major routes are chromosomal instability [CIN], microsatellite instability [MSI], and inflammatory pathways. An earlier study on clinical epidemiology of CRC in Indonesia showed that the majority of patients were diagnosed between 45 and 50 years old, with a mean age around 47 years old. Further studies showed that most young Indonesian cases of CRC do not have hereditary characteristics; however, the CRC did not follow the conventional pathways of sporadic CRC [the CIN] pathway. Rather, it is a mixed of MSI and inflammatory pathways. Immunohistochemical studies showed that the proportion of patients with negative mismatch repair proteins was 43.5% for MSH2 and 83.5% for MLH1. Along the sporadic colorectal carcinogenesis pathway, there was a specific role of cyclooxygenase-2 [COX-2] enzyme during the polyp formation. COX-2 expression was reported in about 80% CRC cases worldwide. However, our study found only 49% of COX-2 expression among the CRC patients. Interestingly, an inflammatory marker, the nucleus factor [k]B [NF-[k]B], was expressed in about 73.5% cases, in line with a previous study. More recently, KRAS has been used as a potential tumor marker to select treatment and its expression was reported to be as high as 30%-40% worldwide. However, we found that KRAS gene expression was only 16.3%. Our findings support that CRC patients in Indonesian might follow a distinct pathway, a hypothesis that deserves further exploration