Project Description Narrative:
Water pollution, particularly in the Great Lakes region, has been a concern due to its potential impact on human health and the environment in Wisconsin, Michigan, Illinois, and Minnesota. Certain pollutants, such as heavy metals, pesticides, industrial chemicals, and other contaminants, can enter water bodies like the Great Lakes through various sources, including industrial discharges, agricultural runoff, and urban stormwater runoff. These pollutants can accumulate in the environment and have the potential to impose various adverse effects on ecosystems and human health, including potential associations with cancer incidence on those who rely on this water for drinking, recreation, and other activities.
Most of the cancer incidences associated with environmental pollutions are the carcinomas of epithelium such as those of skin, breasts, kidney, liver, lungs, pancreas, and prostate gland. According to reports by American Cancer Society, cancer is the leading cause of death in Wisconsin, with prostate cancer and breast cancer being the most frequently diagnosed cancer in males and females, respectively. The Wisconsin state incidence rate (465.5 per 100,000 patients) was greater than the national rate (442.3 per 100,000 patients) for all cancer sites combined. Notably, lung cancer once again remains the leading cause of cancer deaths among both the sexes in the state, with an annual average of 1,570 men and 1,325 women dying from the disease. When compared to other metropolitan regions countrywide, the Milwaukee metropolitan area has the largest Black-White disparity in the country . In addition, Wisconsin also has the third-largest Black-White disparity in breast cancer mortality in the country.
On this background, this project’s research team will explore the unknown mechanisms operated through a class of proteins called RNA binding proteins on the initiation and progression of lung and breast cancer. They have selected NaAsO2, which is a known human carcinogen and an environmental toxin, according to the International Agency for Research on Cancer, to study the mechanism of cellular transformation. Epidemiological studies show that consuming water that has been contaminated with NaAsO2 over a long period of time increases the risk of developing various cancers of the breast, skin, lung, liver, kidney, and bladder. However, it is still unknown how NaAsO2 promotes cancer initiation and progression and how NaAsO2 modulates the functions of an RNA binding protein named G3BP1 (Ras GTPase-activating protein-binding protein 1) for cancer initiation and progression is a critical gap in current knowledge, which will be addressed in this study. The researchers’ hypothesis is that exposure to NaAsO2 promotes the phosphorylation of mitogen-activated protein kinase proteins, subsequently leading to the phosphorylation of G3BP1.