Environmental Exposures And Risk For Cancer and Chronic Diseases In Adults

National Institute Of Environmental Health Sciences

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Abstract

Growing evidence suggests that autoimmunity and certain autoimmune diseases have been increasing in the population, but findings are limited by the lack of systematic data and methodological challenges. Antinuclear antibodies (ANA), a marker of self-reactivity to DNA and other nuclear antigens, are present in several autoimmune diseases and have been observed in healthy persons in the absence of autoimmune disease. In collaborative research using data from the National Health and Nutrition Survey (NHANES) we previously studied whether the prevalence of antinuclear antibodies (ANA), the most common biomarker of autoimmunity, changed over time. Serum ANA were measured by standard indirect immunofluorescence assays on HEp-2 cells in 14,211 participants ages 12 years and older using NHANES data from 1988-1991, 1999-2004, and 2011-2012. The prevalence of ANA was shown to increase from 11.0% in 1988-1991 to 15.9% in 2011-2012. Trends were not explained by obesity or other factors correlated with ANA. The increase was seen for older adults but also among adolescents ages 12-19 years, stimulating new research in our group focused on understanding this trend. One candidate being investigated is a chemical in sunscreens, whose use has also increased over this time period, as well as Vitamin D, which has shown temporal changes in some subgroups in the population. In adolescents and young adults, we found that benzophenone-3 (oxybenzone) concentrations were associated with ANA in the winter sample (Parks et al., in press), and we are presently investigating associations with regular sunscreen use, as well as sunburn history, other sun protective behaviors, and vitamin D. In younger adults and adolescents, we found an association of ANA with "hygiene hypothesis" indicators, including evidence of childhood infections, asthma, and allergy (Meier et al., 2022). The prevalence of ANA is known to increase with aging; the reasons for this are not understood. In a cross-sectional analysis of data from the Baltimore Longitudinal Study of Aging, we previously examined ANA, older age, and associations with type-2 diabetes and multi-morbidity (2 or more chronic diseases). We saw a non-linear relationship between age and ANA that varied by sex, with a clear sex difference in younger participants (ages 48-59), but not in the oldest participants (age 80+). In women, ANA positivity was associated with type 2 diabetes and multi-morbidity, but nothing was seen in men. We are continuing to use these data to examine hypotheses on the role of hormonal factors, including vitamin D, in relation to ANA prevalence and changes in ANA with aging. In a collaboration with Drs. Lisa Rider and Frederick Miller of the NIEHS Environmental Autoimmunity Group, we previously saw an association between the autoimmune condition dermatomyositis and exposure to ultraviolet radiation, including geospatial differences and personal occupational and hobby-related exposures. We are now examining other occupational exposures to silica, metals, and solvents, in relation to myositis phenotype, including respiratory involvement. Autoimmune conditions and their treatments may impact susceptibility to and severity of infections, and response to vaccination. In collaboration with Dr. Rider, we examined factors associated flare requiring a change in treatment following COVID-vaccination among a large international sample of patients with autoimmune rheumatic diseases. The occurrence of flare following vaccination was observed in 4.9% of patients and varied by disease; compared to those with rheumatoid arthritis, some patients, including those with systemic lupus erythematosus, psoriasis, and polymyalgia rheumatica, had significantly higher odds of flare, whereas patients with idiopathic inflammatory myopathies had lower odds of flare following vaccination. If replicated in prospective studies with data on medications and disease activity, these findings may lead to personalized recommendations or precautions surrounding vaccination in autoimmune disease patients. In collaboration with Drs. Meyer and Santos, from the Federal University of Rio de Janeiro in Brazil, we are examining pesticides, autoimmunity, and kidney disease. Recently, in a study of healthy individuals (farmers and controls) in an agricultural community, we found that the occupational use of specific pesticides and fertilizers was associated with markers of oxidative stress (Santos et al., 2021), and with ANA and anti-cyclic citrullinated peptide antibodies (often found in rheumatoid arthritis)(Santos et al., 2022). Pesticides and farming occupation may also be related to acute kidney injury and chronic kidney disease. Using death certificate data from 1980-2014 in two Brazilian regions with intense pesticide use, we examined trends in morality with acute kidney injury (AKI); increasing trends were seen from the mid-1900s to mid-2000s, and in rural areas, in municipalities with higher pesticide expenditures (Meyer et al., 2022). In a case-control analysis, agricultural occupation was associated with greater AKI mortality, especially at younger ages, in females, and in the Southern region. We are currently examining trends in chronic kidney disease mortality in relation to agricultural occupation and pesticide expenditures, and between pesticide expenditures and hospitalization with several types of autoimmune diseases. Autoimmune diseases include over 100 chronic, incurable conditions of complex etiology including the interaction of genetic susceptibility factors with environmental exposures that initiate or promote the development of disease. Systemic Lupus Erythematosus (SLE), is a prototypical systemic autoimmune disease predominately impacting women, especially those of reproductive ages, and with greater rates in African Americans. Increasing evidence provides evidence that several different types of exposures may play a role in SLE, including occupational exposures to silica, pesticides, and other chemicals, smoking, air pollution, and certain chronic infections. Updating previous reviews by Dr. Parks, we recently summarized the state of the science for these and other findings (Woo et al., 2022).