Bio: Meilin Wang, Professor from the School of Public Health, Nanjing Medical University. He is currently the director of the Human Resource of Nanjing Medical University and the deputy director of the Key Laboratory of Modern Toxicology, Ministry of Education. He is mainly engaged in research on environment, genetic/epigenetic and cancer, and molecular epidemiology. His research have been published extensively in international journals including Genome Medicine, Nature Communications, Nucleic Acids Research and Environmental Science & Technology. He has received several research grants, including an Excellent Youth Fund of National Natural Science Foundation of China, Jiangsu Province Natural Science Foundation Outstanding Youth project.

Abstract: Colorectal cancer is the third most common malignancy, with its etiology involving various genetic and environmental factors. Elemental pollution is widespread in the environment and food chain. Epidemiological evidence indicates that heavy metals, including cadmium (Cd), lead (Pb) and thallium (Tl), significantly increase cancer risk. Our study investigates the impact and mechanisms of key elemental exposures associated with colorectal cancer. Plasma concentrations of 56 elements were measured in 208 colorectal cancer patients and 219 controls using ICP-MS. Additionally, 1,150 colorectal cancer patients and 1,342 controls were recruited to assess whether genetic variants influence susceptibility. The acute toxicity and chronic malignant transformation induced by toxic element exposure were also evaluated in normal colon cells and nude mice. This study provides the first comprehensive evaluation of the relationship between elemental exposure and increased colorectal cancer risk based on elemental genomics, identifying Tl as a significant metal influencing cancer risk. Results show that Tl promoted colorectal tumorigenesis by increasing abnormal m6A modification of ATP13A3 through the METLL3/METTL14/ALKBH5-ATP13A3 axis. Our findings provide a foundation for public health strategies to reduce metal exposure in high-risk individuals and offer insights into the epigenetic mechanisms underlying heavy metal-induced colorectal cancer.