Role of Heavy Metals in Colorectal Cancer

Principle investigator: Mohammad Hassan Emami

Co-investigators: Fatemeh Maghool , Abdolmehdi Baghaei , Marjan Mansourian, Ziba Farajzadegan , Nizal  Sarrafzadegan, Nahid Jamali.

Colorectal cancer (CRC) is third most common cancer worldwide. The role of Heavy metals (HMs) in the development and inhibition of cancer has a complex character and raises many questions. Non-essential metals may mimic the essential metals causing a disruption in cellular and enzymatic mechanisms. Therefore, for the precise study of heavy metals, change the profile of essential and non-essential elements should be examined.

Recently, several studies have revealed that heavy metal exposure could also lead to gut microbiota dysbiosis, indicating that study of gut microbiota provides a new approach to analyze the mechanisms of heavy metal toxicity. Dysbiosis of the GI microbiota is associated with many disease susceptibilities including malignancies. Trimethylamine-N-oxide (TMAO) is exclusively generated by the gut microbiota from dietary phosphatidylcholine and choline. Recent studies have shown that elevated TMAO levels strongly predict cardiovascular diseases (CVDs). Whether HMs profile could change plasma levels of TMAO and possible association between plasma TMAO levels and risk of CRC have not yet been clarified.

Understanding possible changes in HMs homeostasis may provide opportunities for the development of effective diagnostic and preventive methods to reduce incidence of CRC. To achieve this goal, we have designed a 3.5 years study to find the difference between heavy metal loads/profiles in the CRC compared to that in control groups. Furthermore, we will examine the plasma concentrations of gut microbial metabolites for indirect assessing the possible dysbiosis. Fecal sampling and DNA extraction will be performed for future studies. If funds will be provided, sampling will continue twice and within 2 years intervals. This study could be a basis of cohort studies by following the control groups with different profiles of HMs as predictive factors for CRC; as well as the case group for the study of CRC prognosis.