Risk Factors and Biomarkers for Early Detection and Prevention of Chronic Diseases

Abstract

In the United States (US), cancer is the second leading cause of death with 1.7 million new cases and 600,000 cancer deaths expected to occur in 2019. Gastric cancer (GC) is the fifth most diagnosed cancer; in the US, around 27,000 new GC cases are expected to occur in 2020. Colorectal cancer (CRC) is the third most commonly diagnosed cancer in men and women. In 2020, in the US, over 145,000 new CRC cases are expected to occur. Another chronic disease of concern is chronic kidney disease (CKD). Currently, about 37 million people in the US are estimated to have CKD. In general, chronic diseases, such as these three, can be managed through prevention strategies which could be primary, secondary, or tertiary, and can be implemented at different points over the course of the disease. Thus, this dissertation work explored the epidemiology and development of these three diseases, and which groups they impact the most, so that gaps can be identified and early detection can occur. Subsequently, prevention methods can be implemented, suitable recommendations can be made, and appropriate treatments can be offered in a timely manner. In the first aim of this dissertation, Surveillance, Epidemiology and End Results (SEER)-Medicare data from 1997 to 2010 were used to determine if there are any differences in GC presentation and screening services, such as Helicobacter pylori (H. pylori), by race/ethnicity, place of birth, and history of GC-related conditions. In this study population, overall, 57.9% had an established condition for which H. pylori testing was recommended; H. pylori infection is strongly associated with non-cardia GC. However, of these, only 11.6% were tested for the bacterium. When broken down by race/ethnicity, this gap in testing was even more apparent. As a way of primary prevention, US-born high-risk populations, in particular black and Hispanic communities, should be educated early on about the various risk factors, including H. pylori, and potential symptoms. In regards to secondary prevention, both patients and physicians need to be aware of the ACG recommendation for those with a history of GC-related conditions. In the second aim, clinical trial data were used to determine if fibroblast growth factor (FGF-21) is associated with metachronous colorectal adenomas. A recent study found an association between FGF-21 and risk of CRC. Here, it was found that, in a mostly older, white male population, there is an increased risk of metachronous adenoma with increased concentrations of FGF-21. FGF-21 could play a role as a diagnostic biomarker for CRC and could be further investigated in order to become a primary prevention strategy to detect those at risk of developing CRC. Furthermore, as a way of secondary prevention, FGF-21 levels could also be closely monitored in those with a personal history of polyps or who have chronic inflammation. Lastly, in the third aim, National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2014 were used to determine if there are any differences in CKD awareness by race/ethnicity, sex, income, health insurance status, and education. The study found that 18% of the NHANES respondents had CKD, but 91.5% self-reported they did not have weak or failing kidneys, thus making them unaware. More specifically, women and older individuals were found to be less aware of having CKD. For primary prevention strategies, providers could focus on women and those who are older, and bring their attention to their kidney function and what their eGFR means. Then, to prevent or delay progression to more advanced stages, secondary and tertiary prevention strategies such as, controlling blood sugar levels and avoiding potassium-rich foods, can be implemented. The work presented here has given insight into possible prevention strategies that could be implemented for these three chronic diseases. Through these strategies, early detection, prevention, and better management can occur, and together they can slow the progression of the disease. Overall, identifying the gaps in the prevention efforts can help remedy them, and identifying which groups need them the most can help tailor prevention strategies to communities most at risk.