Occupational Exposure to Heavy Metal Initiate Carcinogenesis Though BRAF/KRAS Over Expression and DNA Methylation

Abstract

Colorectal carcinoma (CRC) is a leading cause of death especially in industries worker. The aim of this study is to identify the role of heavy elements exposure on CRC DNA methylation.The study was conducted on 25 CRC patients. Biopsies were taken by colonoscopy from malignant tissue and adjacent normal tissues for comparative assessment of BRAF/KRAS, methylated MLH1 and MGMT between the normal and malignant tissues by using real time PCR. In an attempt to identify wither heavy metal like Lead, Aluminum and Mn have a role in cancer development or not, we compared their levels in the serum of 25 CRC patients and 25 normal volunteers by using atomic absorption. The expressions of BRAF/KRAS, methylated MLH1 and MGMT were significantly higher in malignant tissues compared to normal tissues (p value<0.001). Additionally, the levels of lead and aluminum but not Mn were statistically significantly increased in CRC patients compared to normal controls (p value<0.001). Lead and Aluminum were positively correlated with all studied parameters. Heavy metals act as starting signals for carcinogenesis through DNA methylation.