Prenatal Arsenic Exposure on DNA Methylation of C18ORF8 and ADAMTS9 Genes of Newborns from the POSGRAD Birth Cohort Study.

ABSTRACT

Exposure to arsenic (As) is a public health problem associated with cancer (skin and colon) and it has been reported that epigenetic changes may be a potential mechanism of As carcinogenesis. It is pertinent to evaluate this process in genes that have been associated with cancer, such as ADAMTS9 and C18ORF8. Gestation and delivery data were obtained from the POSGRAD study. Exposure to As was measured in urine during pregnancy. Gene methylation was performed by sodium bisulfite sequencing; 26 CpG sites for the C18ORF8 gene and 21 for ADAMTS9 were analyzed. These sites are located on the CpG islands near the start of transcription. Sociodemographic characteristics were obtained by a questionnaire. The statistical analysis was performed using multiple linear regression models adjusted for potential confounders. Newborns with an As exposure above 49.4 µg g-1 showed a decrease of 0.21% on the methylation rate in the sites CpG15, CpG19, and CpG21 of the C18ORF8 gene (adjusted ß = -0.21, p-value = 0.02). No statistically significant association was found between prenatal exposure to As and methylation of the ADAMTS9 gene. Prenatal exposure to As was associated with decreased DNA methylation at the CpG15, CpG19, and CpG21 sites of the C18ORF8 gene. These sites can provide information to elucidate epigenetic mechanisms associated with prenatal exposure to As and cancer.