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

• 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
• 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

§ 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.

§ 项目摘要 睾丸癌虽然在一般人群中很少见，但在年轻人中占所有癌症的60%左右。 20-40岁的男性。它的发病率在世纪增加了几倍，但原因是 大部分都是未知的。确定的风险因素包括隐睾症，高加索种族以及家庭 睾丸癌的历史和科学家强烈怀疑，环境暴露，特别是在 胎儿发育可能起作用。内分泌干扰假说认为， 在胎儿发育过程中，干扰性化学物质（EDCs）会干扰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。尽管紧张不安- 在过去的20年里，cern和巨大的科学和公众关注，流行病学数据仍然是 稀疏。该条件在人群中罕见，胎儿发育的敏感期与胎儿发育的敏感期之间的滞后时间长， 睾丸癌的发病率和临床表现以及缺乏合适的动物模型， 对这种癌症的发展所涉及的因素的理解， 已经量化了产前暴露于EDCs，并且无法解决胎儿睾丸癌的风险。 暴露。因此，有必要进行基于流行病学的研究，并提供基于世博会的可靠数据。 在产前生物样本中进行量化的可靠评估，被认为是黄金标准。的 本提案的目的是利用一组128 702名妇女解决这一知识差距， 在1976- 1996年怀孕期间提供了血液和羊水样本。通过注册表链接- 在高度可靠的国家人口和疾病登记系统中确定结局/潜力的年龄- 我们将确定所有诊断为睾丸癌（包括亚型）的儿子，并匹配 使用风险集抽样，将这些在诊断时的每一个与两个对照儿子（n=550个儿子）进行比较。水平 内分泌干扰物，包括滴滴涕、DDE和其他有机氯农药、多氯联苯、多溴联苯醚、PFAS、邻苯二甲酸盐， 将对母亲产前生物样本中的三氯生进行定量。这项研究对于 国家环境卫生科学研究所的总体使命，并将为国家环境卫生科学研究所的发展做出贡献。 主要是支持或反对胎儿编程假设的证据的权重， 睾丸癌和环境内分泌干扰物在美国还没有进行过类似的研究。阐明 相关环境内分泌干扰物与睾丸癌之间的关联可能揭示潜在的修饰- 易受影响的风险因素，从而为孕妇制定了指导方针，使她们能够采取合理的措施， 自己的曝光。

项目成果

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

• DOI: 10.1016/j.envint.2021.106987
• 发表时间: 2022-01
• 期刊: Environment international
• 影响因子: 11.8
• 作者: Bräuner EV;Uldbjerg CS;Lim YH;Gregersen LS;Krause M;Frederiksen H;Andersson AM
• 通讯作者: Andersson AM

Evaporation of serum after long-term biobank storage: A chemical analysis of maternal serum from a large Danish pregnancy screening registry.

• DOI: 10.1371/journal.pone.0293527
• 发表时间: 2023
• 期刊: PloS one
• 影响因子: 3.7

Is male gynaecomastia associated with an increased risk of death? A nationwide register-based cohort study.

雄性妇科是否与死亡风险增加有关？一项基于全国登记册的同类研究。

• DOI: 10.1136/bmjopen-2023-076608
• 发表时间: 2024-01-16
• 期刊: BMJ OPEN
• 影响因子: 2.9
• 作者: Brauner, Elvira, V;Uldbjerg, Cecilie;Lim, Youn-Hee;Beck, Astrid;Hueg, Trine;Juul, Anders
• 通讯作者: Juul, Anders

Maternal Serum α-Fetoprotein Levels during Pregnancy and Testicular Cancer in Male Offspring: A Cohort Study within a Danish Pregnancy Screening Registry.

• DOI: 10.3390/ijerph192114112
• 发表时间: 2022-10-28
• 期刊: INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
• 作者: Uldbjerg, Cecilie S.;Lim, Youn-Hee;Glazer, Clara H.;Hauser, Russ;Juul, Anders;Brauner, Elvira, V
• 通讯作者: Brauner, Elvira, V

Maternal Exposure to Cigarette Smoke during Pregnancy and Testicular Cancer in Offspring: A Systematic Review and Meta-Analysis.

• DOI: 10.3390/life13030618
• 发表时间: 2023-02-23
• 期刊: Life (Basel, Switzerland)
• 作者: Beck AL;Bräuner EV;Hauser R;Lim YH;Uldbjerg CS;Juul A
• 通讯作者: Juul A