Environmental Exposures And Risk For Cancer and Chronic Diseases In Adults

National Institute Of Environmental Health Sciences

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Abstract

Using data from the US National Health and Examination Survey (NHANES), we studied factors associated with antinuclear antibodies (ANA), including vitamin D and medication use. We also studied the the relationship of ANA with mortality risk (all-cause, cardiovascular disease and cancer). Findings from this work motivated additional analysis of ANA in relation to vitamin D in middle age and older adults, using data from the Baltimore Longitudinal Study of Aging. This work was carried out in collaboration with investigators from the National Institute on Aging (NIA). Recent work using the BLSA focuses on changes in ANA levels over time, explores factors associated with ANA levels and trajectories, and evaluates whether ANA levels are associated with telomere shortening over time. A manuscript was submitted that describes associations of ANA with age and health status. Recently published work focused on ANA and telomere length. Age-associated increases in antinuclear antibodies (ANA) in the general population have been reported but the mechanism is unclear. We evaluated whether shorter peripheral blood mononuclear cell (PBMC) telomere length, a marker of more advanced biological age, was associated with ANA positivity prevalence and incidence in middle and older aged autoimmune disease-free individuals from the Baltimore Longitudinal Study of Aging using data from two time-points. We estimated the odds of ANA positivity comparing the shorter tertiles of telomere length to the longest tertile at two cross-sectional points in time and then longitudinally to assess the association between shorter telomere length and incident ANA positivity. No statistically significant cross-sectional associations were observed at baseline (N=360)or follow-up (N=370). Among those who were ANA negative at baseline (N=246), individuals with shorter telomeres were more likely to be ANA positive at follow-up, an average 13 years later. Findings suggest that ANA positivity in the general population may be indicative of immune dysfunction resulting from advanced cellular aging processes (Meier et al., 2019). In another study, we explored associations between use of pesticides and ANA positivity since farming and pesticide use (e.g. organochlorine insecticides)have been associated with systemic autoimmune diseases. We measured serum antinuclear autoantibodies (ANA) by immunofluorescence on Hep-2 cells in 668 male farmers in the study of Biomarkers of Exposure and Effect in Agriculture (BEEA; 2010-2013), an Agricultural Health Study (AHS) subcohort. We examined ANA in relation to lifetime use of 46 pesticides first reported at AHS enrollment (1993-1997) and updated at intervals through BEEA enrollment. Having ANA antibodies (3 or 4+ intensity at a 1:80 dilution, 21% of study participants) was associated with a reported history of seeking medical care due to exposure to pesticides and with use of specific pesticides including the fumigant methyl bromide, petroleum oil/distillates and, using a higher threshold (3 or 4+ at a 1:160 dilution, 9%) to define ANA positivity, with the carbamate insecticide aldicarb. Furthermore, greater combined use of four cyclodiene organochlorine insecticides was also associated with ANA. Findings suggest that specific pesticide exposures may have long-term effects on ANA prevalence and support the hypothesis that certain organochlorine insecticides may increase the risk of developing systemic autoimmunity (Parks et al., 2019).