Prenatal Exposure to Endocrine Disrupting Chemicals and Risk of Testicular Cancer (DISRUPT)

产前接触内分泌干扰化学物质与睾丸癌 (DISRUPT) 的风险

基本信息

批准号：
10373985
负责人：
Anders Juul
金额：
$ 26.18万
依托单位：
REGION HOVEDSTADEN
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-15 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10373985
关键词：
Address Adolescence Adult Age Amniotic Fluid Analytical Chemistry Androgens Animal Model Appearance Attention Biological Biometry Birth Blood Body mass index Caucasians Chemical Exposure Chemicals Clinical Collection Confounding Factors (Epidemiology)Country Cryptorchidism Data Denmark Developed Countries Development Diagnosis Elderly Endocrine Disruptors Endocrine disruption Endocrinology Environmental Exposure Environmental Pollutants Epidemiology Epigenetic Process Equilibrium Estrogens Ethnic Origin Etiology European Exposure to Family Family history of Fetal Development Fetus Funding Opportunities Gene Expression General Population Gold Guidelines Health Healthcare Histologic Homeostasis Hormones Human Incidence Individual Knowledge Life Life Style Malignant Neoplasms Malignant neoplasm of testis Masculine Maternal Exposure Measures Mission Mothers National Institute of Environmental Health Sciences Notification Occupations Outcome Persons Play Polychlorinated Biphenyls Population Pregnancy Pregnant Women Proxy Puberty Questionnaires Recording of previous events Registries Reproductive Health Research Research Project Grants Research Proposals Risk Risk Factors Role Sampling Scientist Serum Son Specific qualifier value System TNM Time Triclosan United States National Institutes of Health Weight Woman aged base cancer risk case control cohort cost effective disease registry epidemiologic data epidemiology study fetal in utero infancy male men modifiable risk multidisciplinary neoplasm registry novel offspring organ growth organochlorine pesticide phthalates pregnant prenatal prenatal exposure programs prospective rare condition reproductive reproductive organ trend young adult young man

项目摘要

§ Project Summary Testicular cancer, although rare in the general population, represents around 60% of all cancers in young men aged 20-40 years. Its incidence has increased several-fold during the 20th century, but reasons for this are largely unknown. Established risk factors include cryptorchidism, Caucasian ethnicity as well as family history of testicular cancer and scientists strongly suspect that environmental exposures particularly during fetal development may play a role. The endocrine disruption hypothesis suggests that exposure to endocrine disrupting chemicals (EDCs) during fetal development disrupts normal reproductive organ development associated with long-term adverse reproductive effects, including testicular cancer. Despite heightened con- cern and tremendous scientific and public attention during the past 20 years, epidemiological data are still sparse. The conditions rarity in the population, long lag time between the sensitive period during fetal de- velopment and clinical appearance and lack of appropriate animal models for testicular cancer have hin- dered the understanding of the factors involved in the development of this cancer and few if any studies have quantified prenatal exposure to EDCs and were unable to address risk of testicular cancer from fetal exposures. Therefore, there is a need for epidemiological based research with reliable data based on expo- sure assessment quantified in biological prenatal samples, which are considered the gold standard. The objective of the present proposal is to address this knowledge gap using a cohort of 128,702 women who provided blood and amniotic fluid samples during their pregnancies in the period 1976-96. By registry link- age within highly reliable national population and disease registries for ascertainment for outcome/poten- tial confounders we will identify all sons diagnosed with testicular cancer (including sub-types) and match each of these at the time of their diagnosis to two control sons (n=550 sons) using risk set sampling. Levels of EDCs including DDT, DDE and other organochlorine pesticides, PCBs, PBDEs, PFAS, phthalates and triclosan will be quantified in prenatal biosamples from mothers. This study is important in relation to the overall mission of the National Institute of Environmental Health Sciences and will contribute substan- tially to the weight of the evidence in support of or against the fetal programing hypothesis with respect to testicular cancer and environmental EDCs. No similar research has been carried out in the US. Elucidating the association between relevant environmental EDCs and testicular cancer may reveal potentially modifia- ble risk factors, leading to guidelines for pregnant women so they can take sensible measures to reduce their own exposures.

§ 项目概要睾丸癌虽然在一般人群中很少见，但约占年轻人所有癌症的 60% 20-40岁男性的发病率在20世纪增加了数倍，但其原因如下。已知的风险因素包括隐睾症、白人种族以及家庭。睾丸癌的历史和科学家强烈怀疑环境暴露，特别是在内分泌干扰假说表明胎儿发育可能发挥一定作用。胎儿发育过程中的干扰化学物质 (EDC) 会破坏正常的生殖器官发育与长期不良生殖影响有关，包括睾丸癌。过去 20 年来，尽管欧洲核子研究中心 (CERN) 以及科学界和公众的巨大关注，流行病学数据仍然人口稀少，胎儿脱胎的敏感期之间的滞后时间长。睾丸癌的发展和临床表现以及缺乏适当的动物模型表明人们对这种癌症发展所涉及的因素的了解很少，如果有的话已量化产前 EDC 暴露，但无法解决胎儿患睾丸癌的风险因此，需要进行基于流行病学的研究，并提供基于暴露的可靠数据。在生物产前样本中进行确定的评估，这被认为是金标准。本提案的目标是利用 128,702 名女性群体来弥补这一知识差距提供了 1976-96 年间怀孕期间的血液和羊水样本。高度可靠的国家人口和疾病登记中的年龄，以确定结果/潜力对于这些混杂因素，我们将识别所有被诊断患有睾丸癌（包括亚型）的儿子并进行匹配使用风险集水平抽样对两个对照儿子（n = 550 儿子）进行诊断时的每一项。 EDC 包括 DDT、DDE 和其他有机氯农药、PCB、PBDE、PFAS、邻苯二甲酸盐和这项研究对于母亲的产前生物样本中的三氯生很重要。国家环境健康科学研究所的总体使命并将做出实质性贡献主要取决于支持或反对胎儿编程假说的证据的权重美国尚未开展类似的研究来阐明睾丸癌和环境 EDC。相关环境 EDC 与睾丸癌之间的关联可能揭示潜在的改变 BLE 风险因素，从而制定针对孕妇的指南，以便她们能够采取明智的措施来减少风险自己的曝光。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Presence of parabens, phenols and phthalates in paired maternal serum, urine and amniotic fluid.

配对母体血清、尿液和羊水中存在对羟基苯甲酸酯、苯酚和邻苯二甲酸盐。

DOI：
发表时间：
2022-01
期刊：
影响因子：
11.8
作者：
Bräuner, Elvira V;Uldbjerg, Cecilie S;Lim, Youn;Gregersen, Laura S;Krause, Marianna;Frederiksen, Hanne;Andersson, Anna
通讯作者：
Andersson, Anna

Endocrine Disrupting Chemicals and Risk of Testicular Cancer: A Systematic Review and Meta-analysis.

内分泌干扰化学物质和睾丸癌的风险：系统评价和荟萃分析。

DOI：
发表时间：
2021
期刊：
影响因子：
0
作者：
Bräuner, Elvira V;Lim, Youn;Koch, Trine;Uldbjerg, Cecilie S;Gregersen, Laura S;Pedersen, Marc K;Frederiksen, Hanne;Petersen, Jørgen H;Coull, Brent A;Andersson, Anna;Hickey, Martha;Skakkebæk, Niels E;Hauser, Russ;Juul, Anders
通讯作者：
Juul, Anders

Cotinine concentrations in maternal serum and amniotic fluid during pregnancy and risk of testicular germ cell cancer in the offspring: A prospective nested case-control study.

怀孕期间母体血清和羊水中的可替宁浓度与后代睾丸生殖细胞癌的风险：一项前瞻性巢式病例对照研究。

DOI：
发表时间：
2024-01-01
期刊：
影响因子：
6.4
作者：
Beck, Astrid L;Uldbjerg, Cecilie S;Lim, Youn;Coull, Brent A;Sørensen, Karina M;Utko, Magdalena M;Wilkowski, Bartlomiej;Rantakokko, Panu;Bengtsson, Marie;Lindh, Christian;Petersen, Jørgen H;Skakkebaek, Niels E;Hauser, Russ;Juul, Anders;Br
通讯作者：
Br

Increased Morbidity in Males Diagnosed With Gynecomastia: A Nationwide Register-based Cohort Study.

诊断为男性乳房发育症的男性发病率增加：一项基于全国登记的队列研究。