Modulation Effect of Folate on the Association Between Inorganic Arsenic and Aggressive Prostate Cancer
Abstract
Arsenic is a toxic trace element that is distributed throughout the Earth’s surface and is considered a global public health concern. However, despite arsenic is ranked number one on the Agency for Toxic Substances and Disease Registries list of hazardous substances, the health impact from arsenic has been thought as the problem only for the developing countries. In fact, the exposure to arsenic is not limited to high arsenic pollution areas because the general population can be affected by consuming contaminated food items in the U.S. For example, a study of more than 204 rice samples sold in U.S. markets found that the rice grown in Arkansas and Texas has the highest content of arsenic compared to rice imported from Asia or grown in California. Almost half (49%) of the U.S. s total rice production was produced in Arkansas; and Texas has the fifth highest rice production. The Food and Drug Administration released a report in 2021 highlighting many of infant cereals and baby foods in the U.S. market also contain dangerous level of arsenic. Environmental contamination by arsenic in the soil in many parts of the country has been documented by the U.S. Geological Survey. Rural residents of racial/ethnic minorities are more likely to be exposed throughout their lives than those in cities because much of the vegetation grown in this area has a potentially higher content of arsenic. Furthermore, military personnel were exposed to arsenic and other heavy metals from metal-containing particulates in smoke from destroyed vehicles and open-air burn pits. Chronic arsenic exposure is associated with increased prostate cancer incidence and mortality. Considering arsenic does not degrade easily and is very slow to excrete once enters human body, strategies are needed to address the risk of aggressive prostate cancer from arsenic exposure in the under-representative minority population and exposed military personnel. Earlier animal and observational studies have reported that folate decreased the risk of prostate cancer. However, findings from clinical trials of folate supplement and biomarker studies are inconsistent. The beneficial effect of folate in cancer prevention is still subject to debate. Our earlier study using the same study population found that increase consumption of folate is associated with lower likelihood of aggressive prostate cancer in European Americans but not African Americans. The finding suggests that other factors may be involved in the relationship between folate and prostate cancer. Arsenic metabolism involves a folate dependent process to transform the more toxic form of arsenic to forms that are more easily to be excreted. A double-blind placebo-controlled trial in a population with low plasma folate observed that the proportion of total urinary arsenic excreted as DMA increased and blood arsenic concentration decreased after 12 weeks of folic acid supplementation. Arsenic can affect how the genes in our DNA work, and it is suggested that this can increase the risk of developing prostate cancer or enhance the progression of the cancer. Based on this evidence, we hypothesize that folate can modify the harmful impact of arsenic on the development and progression into aggressive prostate cancer by transforming arsenic in the body into excretable forms. Folate can also modulate the effect from arsenic on the DNA methylation of genes that are involved in cancer development. We also hypothesize that African American men are more likely to be exposed to arsenic than European American men such that it contributes to the racial disparity for prostate cancer outcomes. Arsenic in toenail have been considered as the best choice of markers for long-term exposure. We will test our study hypotheses using the sample and data previously collected in the North Carolina – Louisiana Prostate Cancer Project (PCaP). PCaP is a multidisciplinary, population-based, case-only study investigating racial
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310924
Entities
People
- Lih Chyun Su
Organizations
- United States Army
- University of Texas Southwestern Medical Center