Statistical Consulting Service: Epidemiologic Research

研究环境因素对人类健康的影响是该研究所使命的重要组成部分。由于这些研究几乎总是观察性的，而不是实验性的，数据的解释是复杂的。在所有阶段，包括概念、设计、分析和解释，良好的统计合作对这项工作的成功至关重要。 在这一年里，我们在许多项目上都是积极的合作者。这些研究包括关于产前和儿童期接触及其对儿童健康的影响的研究、关于成人疾病与环境接触之间关系的研究以及旨在更好地了解某些生殖条件的生物学的研究。 我们研究了波兰儿童铅浓度的社会经济预测因素;了解暴露源以防止未来暴露至关重要。我们还研究了早期暴露于各种化合物对儿童后期健康结果的可能后果。我们使用了两个人群，一个是20世纪60年代出生的美国儿童，另一个是20世纪90年代出生的乌克兰儿童，他们出生在一个报告了污染问题的地区，来研究产前接触有机氯与出生体重和早产之间的关系。美国的队列研究也被用来检查产前暴露于抗雄激素化合物DDE是否与男性生殖器出生缺陷有关。它还被用来检查产前接触多氯联苯是否与儿童随后的智力和运动发育有关。在乌克兰队列中评估了妊娠并发症（根据入院情况评估）。我们还使用了最近美国一项大型调查的数据来研究母乳喂养是否可以预防哮喘的发展。 研究了若干成人疾病与环境暴露之间的关系。我们使用了一个大型的农民研究，农业健康研究，以研究农药和其他农业暴露与喘息的可能关系。在一项非霍奇金淋巴瘤的病例对照研究中，农业和生活方式因素都被视为可能的预测因素。研究了肺癌与空气污染和氡的关系。还研究了糖尿病与多氯联苯之间的可能关系。 对一些生殖条件和疾病进行了研究。为了了解这些疾病可能的环境影响，需要基础的基本知识。子宫肌瘤（平滑肌瘤）的病因知之甚少。甚至发病率也没有得到很好的确定;我们检查了发病率和作为风险因素的胎次的作用。先兆子痫是另一个研究不足的条件;我们研究了这种疾病的几个危险因素。此外，我们还研究了妊娠的多个方面，包括妊娠早期正常事件和并发症的几项检查、人绒毛膜促性腺激素在成功妊娠中的作用、某些多态性与宫内发育迟缓的关系以及胎盘重量作为衡量出生大小的有用性。 上述一些研究是正在进行的工作，将继续下去。此外，目前还没有结果的新项目正在进行中。下面简要介绍其中一些项目。 我们将研究青春期的身体大小和产前暴露于DDT/DDE之间的关系，在一个队列的300名男孩出生于20世纪60年代。人体测量数据和储存的母亲血液样本已经存在，目前正在测量血液中的滴滴涕/DDE浓度。这是一个试图复制在以前的NIEHS研究中看到的发现，在该研究中，产前接触DDE的男孩比其他男孩更高更重。 我们将研究产前暴露于抗雄激素化合物DDE和出生时肛门生殖器距离之间的关系，在墨西哥的人口与相对较高的暴露于滴滴涕。 我们正处于计划和协议的发展阶段，研究DDE对早期绝经的影响。这项研究将在NIEHS先前研究过的儿童的母亲中进行。可获得妊娠期间的DDE测量值，并将进行有关绝经状态的问卷调查。 我们正在合作研究纤维瘤生长动力学。将对300名患有子宫肌瘤的女性进行MRI随访，以确定肌瘤的生长模式;对于接受手术的女性，将获得组织。还将研究子宫肌瘤的预测因素和临床后果。预测因素包括生物因素，如病理学和生活方式因素。今年完成了设计工作，正在收集数据。 我们正在设计一项临床研究，以确定在切除肺肿瘤时，首先结扎动脉或静脉是否会影响远处转移的发展。该研究目前正在通过批准程序。 我们正在对乳腺癌患者未受影响的姐妹篇进行一项大型队列研究。大约50000名姐妹篇将被跟踪至少5年。该研究旨在阐明环境和遗传因素的共同影响，并将允许检查内源性激素、外源性激素干扰物、生长因子（如维生素D和IGF）以及公众关注的环境污染物（如杀虫剂和溶剂）。

Studies of the effects of environmental agents on human health are a vital part of the mission of the institute. As such studies are almost always observational rather than experimental, interpretation of the data is complex. Good statistical collaboration in all phases, including conception, design, analysis, and interpretation, is essential to the success of this work. During the current year, we were active collaborators on many projects. These included studies of prenatal and childhood exposures and their later impacts on the health of children, studies of associations of adult disease with environmental exposures, and studies aimed at better understanding of the biology of certain reproductive conditions. We examined socio-economic predictors of lead concentrations in Polish children; it is vital to understand sources of exposure in order to prevent future exposure. We also examined possible consequences of early-life exposures to various compounds on later health outcomes in children. We used two populations, one of American children born in the 1960s, and one of Ukrainian children born in the 1990s in a region where pollution problems have been reported, to look at the association of prenatal exposure to organochlorines with birth weight and preterm delivery. The American cohort was also used to examine whether prenatal exposure to the anti-androgenic compound DDE was related to male genital birth defects. It was also used to examine whether prenatal exposure to polychlorinated biphenyls was related to subsequent mental and motor development of children. Pregnancy complications, as assessed by hospital admissions, were assessed in the Ukrainian cohort. We also used data from a recent large American survey to examine whether breast-feeding is protective against the development of asthma. Associations of a number of adult diseases with environmental exposures were examined. We used a large study of farmers, the Agricultural Health Study, to examine possible relationships of pesticides and other agricultural exposures to wheezing. In a case-control study of non-Hodgkin's lymphoma, both agricultural and lifestyle factors were examined as possible predictors. Associations of lung cancer with both air pollution and radon were examined. Possible relationships of diabetes and polychlorinated biphenyls were also examined. A number of reproductive conditions and disorders were studied. A base of basic knowledge is needed in order to understand possible environmental influences on these disorders. The etiology of uterine fibroids (leiomyomas) is poorly understood. Even incidence is not well established; we examined incidence rates and the role of parity as a risk factor. Pre-eclampsia is another understudied condition; we examined several risk factors for this disease. In addition, we studied a number of facets of pregnancy, including several examinations of both normal events and complications in the early stages of pregnancy, the role of human chorionic gonadotropin in successful pregnancy, associations of certain polymorphisms with intrauterine growth retardation, and the usefulness of placental weight as a measure of birth size. A number of the studies mentioned above are ongoing work that will continue. In addition, new projects for which no results are currently available are underway. Brief descriptions of some of these projects follows. We will examine the relationship between adolescent body size and prenatal exposure to DDT/DDE in a cohort of 300 boys born in the 1960s. Anthropometric measurements and stored maternal blood samples exist, and DDT/DDE concentrations in the blood are currrently being measured. This is an attempt to replicate a finding seen in a previous NIEHS study, where boys with higher prenatal exposure to DDE were taller and heavier than other boys. We will examine the relationship between prenatal exposure to the anti-androgenic compound DDE and anogenital distance at birth in a population in Mexico with relatively high exposure to DDT. We are in the planning and protocol development stages for a study of the effects of DDE on early menopause. The study will be done in mothers of children who were studied previously by NIEHS. DDE measurements during pregnancy are available, and questionnaires about menopausal status will be administered. We are collaborating on a study of fibroid growth dynamics. 300 women with uterine leiomyomas will be followed with MRI to determine the growth patterns of the fibroids; for women who undergo surgery, tissue will be obtained. Predictors and clinical consequences of fibroids will also be studied. Predictors include both biological ones, such as pathology, and lifestyle factors. Design work was done this year and data collection is underway. We are working on the design of a clinical study to determine whether, when resecting lung tumors, ligation first of an artery or a vein influences distant metastasis development. The study is currently moving through the approval process. We are working on the development of a large cohort study of unaffected sisters of women with breast cancer. Approximately 50000 sisters will be followed for at least 5 years. The study is designed to clarify the joint effects of environmental and genetic factors, and will allow examination of endogenous hormones, exogenous hormone disruptors, growth factors such as vitamin D and IGF, and environmental contaminants of general public concern such as pesticides and solvents.