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。这项工作的发现促使使用巴尔的摩老龄化纵向研究的数据对ANA与中老年人维生素D的关系进行了进一步的分析。这项工作是与国家老龄研究所(NIA)的研究人员合作进行的。最近使用BLSA的工作集中在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水平是否与随着时间的推移端粒缩短有关。提交了一份手稿，描述了ANA与年龄和健康状况的关系。 最近发表的研究集中在ANA和端粒长度上。一般人群中与年龄相关的抗核抗体(ANA)的增加已有报道，但其机制尚不清楚。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(生物学年龄更高的标志)是否与来自巴尔的摩老龄化纵向研究的中老年自身免疫性疾病非疾病个体的ANA阳性患病率和发病率有关。我们在两个横切点比较端粒长度较短的三分体和最长的三分体，然后纵向评估端粒较短的三分体与入射的ANA阳性之间的关系。在基线(N=360)或随访(N=370)时，没有观察到有统计学意义的横断面关联。在基线(N=246)ANA阴性的患者中，端粒较短的个体在平均13年后的随访中更有可能ANA阳性。研究结果表明，普通人群中ANA阳性可能表明高级细胞衰老过程导致的免疫功能障碍(Meier等人，2019年)。 在另一项研究中，我们探索了杀虫剂的使用和ANA阳性之间的关系，因为农业和杀虫剂的使用(例如有机氯杀虫剂)与系统性自身免疫性疾病有关。在农业健康研究(AHS)亚队列《农业暴露和影响的生物标志物研究》(BEA；2010-2013)中，我们用Hep-2细胞免疫荧光法检测了668名男性农民的血清抗核自身抗体(ANA)。我们检查了ANA与46种杀虫剂终生使用的关系，最初是在AHS登记(1993-1997)中报告的，并通过BEA登记每隔一段时间更新。有ANA抗体(1：80稀释度为3或4+，21%的研究参与者)与报告的因接触杀虫剂和使用特定杀虫剂(包括熏蒸剂甲基溴、石油油/蒸馏物)而寻求医疗护理的病史有关，并使用更高的阈值(1：160稀释度为3或4+，9%)来确定ANA阳性，使用氨基甲酸酯杀虫剂敌百威。此外，更多地联合使用四种环二烯有机氯杀虫剂也与ANA有关。研究结果表明，特定的农药暴露可能对ANA的流行率产生长期影响，并支持某些有机氯杀虫剂可能增加发生系统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).