Environmental Exposures And Risk For Cancer and Chronic Diseases In Adults

使用美国国家健康和检查调查（NHANES）的数据，我们研究了与抗核抗体（ANA）相关的因素，包括维生素D和药物使用。 我们还研究了ANA与死亡风险（全因、心血管疾病和癌症）的关系。这项工作的结果激发了额外的分析ANA与维生素D在中年和老年人，使用数据从巴尔的摩纵向研究老化。这项工作是与国家老龄化研究所（NIA）的研究人员合作进行的。 最近使用BLSA的工作重点是ANA水平随时间的变化，探索与ANA水平和轨迹相关的因素，并评估ANA水平是否与端粒随时间缩短相关。提交了一份描述ANA与年龄和健康状况相关性的手稿。 最近发表的工作集中在ANA和端粒长度。在一般人群中，抗核抗体（ANA）的增加与糖尿病相关，但其机制尚不清楚。在巴尔的摩老龄化纵向研究中，我们使用两个时间点的数据评估了较短的外周血单核细胞（PBMC）端粒长度（更先进的生物学年龄的标志物）是否与ANA阳性患病率和发生率相关。我们估计ANA阳性的几率比较端粒长度的较短的三分位数最长的三分位数在两个横截面的时间点，然后纵向评估较短的端粒长度和事件ANA阳性之间的关联。在基线（N=360）或随访（N=370）时未观察到统计学显著的横断面相关性。在基线时ANA阴性的患者中（N=246），端粒较短的个体在随访时更有可能是ANA阳性，平均13年后。研究结果表明，一般人群中的ANA阳性可能指示由晚期细胞老化过程引起的免疫功能障碍（Meier et al.，2019年）。 在另一项研究中，我们探讨了使用农药和ANA阳性之间的关联，因为农业和农药使用（例如有机氯杀虫剂）与系统性自身免疫性疾病有关。我们通过Hep-2细胞上的免疫荧光法测量了668名男性农民的血清抗核自身抗体（ANA），这些男性农民参加了农业暴露和影响的生物标志物研究（BEEA; 2010-2013），这是一项农业健康研究（AHS）子队列。我们研究了ANA与46种农药的终生使用的关系，这些农药首次在AHS登记时（1993-1997年）报告，并通过BEEA登记定期更新。ANA抗体（1：80稀释时强度为3或4+，21%的研究参与者）与报告的因接触农药和使用特定农药（包括熏蒸剂甲基溴、石油油/蒸馏物）而寻求医疗护理的历史相关，并使用较高的阈值（1：160稀释时强度为3或4+，9%）来定义ANA阳性，使用氨基甲酸酯杀虫剂涕灭威。此外，环二烯类有机氯杀虫剂的联合使用也与ANA有关。研究结果表明，特定的农药暴露可能对ANA患病率产生长期影响，并支持某些有机氯杀虫剂可能增加发生全身性自身免疫的风险的假设（Parks等人，2019年）。

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).