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 (Dinse et al., 2022). ANA prevalence 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. Cross-sectional analyses revealed both positive and negative associations with various chemicals in subgroup analyses, including some PCBs (Dinse et al., 2022). We are also examining specific types of exposures, such as 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 new research, we also describe similar time trends in anti-dense fine speckled 70 (DFS70) autoantibodies, seen in 4% of the U.S. population by 2011-2012, with lower rates in African American compared with white individuals and among current smokers (Dinse et al., 2023). 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. In collaborations with Drs. Meyer and Santos, from the Federal University of Rio de Janeiro in Brazil, we are examining pesticides, autoimmunity, and kidney disease. In healthy individuals (farmers and controls) from an agricultural community, we described associations of occupational use of specific pesticides and fertilizers with markers of oxidative stress, as well as recent findings of pesticide associations with ANA and anti-cyclic citrullinated peptide antibodies (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 are examining trends in kidney morality, following up on findings linking deaths from acute kidney injury with pesticide expenditures and agricultural occupation, now 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 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 and Liu et al., 2022). Growing evidence suggests traumatic stress and early life adversities may be associated with disease incidence. We recently examined recent life events and caregiving in relation to the incidence of systemic autoimmune disease (SLE and RA) in the Women's Health Initiative cohort (Parks et al., 2023). Our results show that women with multiple stressful events and partner abuse within 12-months prior to enrollment had a greater risk of developing disease during the first 3-years of follow-up. In another collaboration, findings from the Personalized Environment and Genes Study Health and Exposure Survey showed that having an autoimmune disease overall or just RA was associated with residential distance to concentrated animal feeding operations (CAFOs; Ayala-Ramirez, 2023), which are related to a variety of exposures, including social and racial disparities. Together these results suggest contextual factors related to environmental and psychosocial stressors may play a role in increasing risk of autoimmune diseases.