Abstract IA23: Cadmium exposure, DNA methylation and liver cancer

Abstract

Abstract Background. In the last 30 years, the incidence of hepatocellular carcinoma (HCC) has increased faster than other solid tumors and race/ethnic disparities are widening, yet suspected risk factors whose prevalence has also been on a parallel increase, cannot fully explain either this steep increase in incidence or the widening racial/ethnic gap. An understudied, yet potent risk-factor whose prevalence has been on the increase and disproportionately affects ethnic minorities, is exposure to environmental contaminants e.g., cadmium—a probable carcinogen whose main target organ is the liver. Methods. We measured cadmium concentrations in maternal blood samples obtained prenatally using inductively coupled plasma mass spectrometry. In umbilical cord blood leukocytes, we measured DNA methylation at a regulatory sequence controlling the expression of the gene cluster that includes DLK1, MEG3, MEG9, MEG8, DIO3 and some SNORD genes. Hyper-methylation at this sequence region—the first exon of MEG3—has been associated with HCC. We used zip-code level North Carolina Cancer Registry data to estimate liver cancer incidence, and Getis-Ord Gi* statistic and regression models to evaluate the relationships among cadmium exposure, MEG3 hyper-methylation and HCC incidence. Results. We found that higher cadmium concentrations were associated with significant MEG3 hypermethylation (p=0.03), and associations were specific to African Americans (p=0.01). We also found a significant geographic cluster of MEG3 hypermethylation, in the zip-code with the highest liver cancer incidence (p=0.01). ~75% of which HCC. Conclusion. Our data suggest that hypermethylation of the sequence that regulates MEG3, an established tumor suppressor is associated with cadmium exposure early life and HCC in adults. A comprehensive characterization of other networks that are altered in response to environmental exposures that disproportionately affect ethnic minorities, is urgently needed. Citation Format: Catherine Hoyo. Cadmium exposure, DNA methylation and liver cancer [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA23.