胎儿发育期间接触全氟烷基和多氟烷基物质与成年后睾丸生殖细胞癌的风险

IF 9.7 1区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Environment International Pub Date : 2025-09-01 DOI:10.1016/j.envint.2025.109762

Cecilie S. Uldbjerg , Youn-Hee Lim , Astrid L. Beck , Jørgen H. Petersen , Karina M. Sørensen , David M. Kristensen , Panu Rantakokko , Brent A. Coull , Christian Lindh , Niels E. Skakkebæk , Russ Hauser , Elvira V. Bräuner , Lærke Priskorn , Anders Juul

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引用次数: 0

摘要

背景：睾丸生殖细胞癌（TGCC）起源于胎儿时期。胎儿接触环境中的化学物质可能有助于其发展，但缺乏流行病学数据。我们调查了全氟烷基和多氟烷基物质（PFAS），它们在胎儿发育过程中可以作为内分泌干扰物，并在成年后发生TGCC的风险。方法采用巢式病例-对照研究，选取549对母-雄子代（103例TGCC， 446例配对对照）。来源人群包括在1985-1994年间收集的100,000多名孕妇的生物血清样本，这是在PFAS限制之前的一段时间。对雄性后代进行了长达38 年的随访，并根据组织学确认从丹麦癌症登记处确定了TGCC病例。采用LC-MS/MS对母体血清中8种PFAS进行定量分析。通过Cox回归和分位数g计算评估单个PFAS及其混合物与TGCC风险之间的关系。结果个体PFAS与TGCC风险之间的关联不大，无统计学意义。全氟烷基磺酸（PFOS、PFHxS、PFHpS）的风险比（hr）表明，浓度每增加四分位数，TGCC风险较高，但全氟烷基羧酸（PFOA、PFNA、PFDA、PFHpA、PFUnDA）的风险较低。混合分析支持这一模式，磺酸联合作用的TGCC风险更高（HR 1.13, 95 % CI: 0.89; 1.44）。组织学亚型的分层分析显示，在所有PFAS中，精原细胞瘤的风险高于非精原细胞瘤。结论：我们发现胎儿PFAS暴露与TGCC风险之间存在关联的证据有限。关于全氟烷基磺酸潜在不利影响的迹象，特别是对精原细胞瘤，值得进一步研究。

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Exposure to per- and polyfluoroalkyl substances during fetal development and risk of testicular germ cell cancer in adulthood

Background

Testicular germ cell cancer (TGCC) originates during fetal life. Fetal exposure to environmental chemicals may contribute to its development, but epidemiological data are lacking. We investigated per- and polyfluoroalkyl substances (PFAS), which can act as endocrine disruptors during fetal development, and TGCC risk in adulthood.

Methods

We conducted a nested case-control study of 549 mother-male offspring pairs (103 TGCC cases, 446 matched controls). The source population included over 100,000 pregnant women with biobanked serum samples collected during 1985–1994, a period before PFAS restrictions. Male offspring were followed for up to 38 years, and TGCC cases were identified from the Danish Cancer Registry based on histological confirmation. Eight PFAS were quantified in maternal serum using LC-MS/MS. Associations between individual PFAS and their mixtures with TGCC risk were assessed through Cox regression and quantile g-computation models.

Results

Associations between individual PFAS and TGCC risk were modest and not statistically significant. Hazard ratios (HRs) for perfluoroalkyl sulfonic acids (PFOS, PFHxS, PFHpS) suggested higher TGCC risks per quartile increase in concentrations, but lower risks for perfluoroalkyl carboxylic acids (PFOA, PFNA, PFDA, PFHpA, PFUnDA). Mixture analyses supported this pattern, with higher TGCC risk for the joint effect of sulfonic acids (HR 1.13, 95 % CI: 0.89; 1.44). Stratified analyses by histological subtype showed higher risk for seminomas than for nonseminomas across all PFAS.

Conclusions

We found limited evidence of an association between fetal PFAS exposure and TGCC risk. Indications of a potential adverse effect of perfluoroalkyl sulfonic acids, particularly for seminomas, merit further research.

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来源期刊

Environment International 环境科学-环境科学

CiteScore

21.90

自引率

3.40%

发文量

734

审稿时长

2.8 months

期刊介绍： Environmental Health publishes manuscripts focusing on critical aspects of environmental and occupational medicine, including studies in toxicology and epidemiology, to illuminate the human health implications of exposure to environmental hazards. The journal adopts an open-access model and practices open peer review. It caters to scientists and practitioners across all environmental science domains, directly or indirectly impacting human health and well-being. With a commitment to enhancing the prevention of environmentally-related health risks, Environmental Health serves as a public health journal for the community and scientists engaged in matters of public health significance concerning the environment.