Serum concentrations of per- and polyfluoroalkyl substances and risk of ovarian cancer.

IF 7.2 1区医学 Q1 ONCOLOGY

JNCI Journal of the National Cancer Institute Pub Date : 2025-08-01 DOI:10.1093/jnci/djaf204

Rena R Jones, Jessica M Madrigal, Danielle N Medgyesi, Jared A Fisher, Antonia M Calafat, Julianne Cook Botelho, Kayoko Kato, Paul S Albert, Debra T Silverman, Jonathan N Hofmann, Britton Trabert

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引用次数: 0

Abstract

Background: Per- and polyfluoroalkyl substances (PFAS) are persistent, widespread environmental contaminants and some are endocrine-disrupting. Studies of gynecologic cancers are limited; we evaluated ovarian cancer, a rare, often fatal malignancy.

Methods: This nested case-control study included 318 ovarian cancer cases and 472 individually matched female controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which recruited participants aged 55-74 years from 10 U.S. study centers (1993-2001). We ascertained cases through 2016 and quantitated eight PFAS in prediagnostic serum samples. We estimated ORs and 95% CIs for continuous (log2-transformed) and categorized PFAS concentrations via conditional logistic regression models implicitly adjusting for matching factors (age, center, randomization year, year of blood draw, race and ethnicity) and adjusted for smoking, body mass index, family history of cancer, menopausal hormone therapy and oral contraceptive use, parity, and number of freeze-thaws.

Results: We found a positive association with ovarian cancer for a doubling in 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA) concentrations (ORperlog2=1.24, CI = 1.03-1.49) and 62% greater risk among those in the highest quartile (ORQ4vsQ1=1.62, CI = 1.03-2.54; p-trend = 0.02). Perfluorooctane sulfonic acid (PFOS) was associated with increased risk (ORperlog2=1.47, CI = 1.05-2.06) with no quartile trend (p-trend = 0.79). Associations with perfluorononanoic (ORperlog2=1.36, CI = 0.95-1.95) and perfluorodecanoic acid (ORperlog2=1.35, CI = 0.94-1.95) were suggested, with non-monotonic quartile trends (p-trend = 0.12-0.21). MeFOSAA associations were strongest in women aged 55-59 (ORperlog2=1.60, CI = 1.13-2.27), more moderate in those 60-64 (ORperlog2=1.31, CI = 0.90-1.90) and null among women 65 + (ORperlog2=1.02, CI = 0.73-1.43; p-heterogeneity = 0.22). Associations persisted in cases diagnosed ≥8 years after blood collection.

Conclusions: These findings offer novel evidence for PFAS as ovarian cancer risk factors, particularly PFOS and MeFOSAA, a PFOS precursor.

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全氟烷基和多氟烷基物质的血清浓度与卵巢癌的风险。

背景：全氟和多氟烷基物质（PFAS）是一种持久性的、广泛存在的环境污染物，其中一些具有内分泌干扰作用。妇科癌症的研究是有限的；我们评估了卵巢癌，一种罕见的，通常是致命的恶性肿瘤。方法：本巢式病例对照研究包括318例卵巢癌病例和472例单独匹配的前列腺癌、肺癌、结直肠癌和卵巢癌筛查试验中的女性对照，该研究招募了来自美国10个国家的55-74岁的参与者研究中心（1993-2001）。我们确定了2016年的病例，并定量分析了诊断前血清样本中的8种PFAS。我们估计了连续（log2转换）的or和95% ci，并通过条件logistic回归模型对PFAS浓度进行了分类，该模型隐式调整了匹配因素（年龄、中心、随机化年份、抽血年份、种族和民族），并调整了吸烟、体重指数、癌症家族史、绝经期激素治疗和口服避孕药的使用、胎次和冻融次数。结果：我们发现2-（n -甲基-全氟辛烷磺酰胺）乙酸（MeFOSAA）浓度加倍与卵巢癌呈正相关（ORperlog2=1.24, CI = 1.03-1.49），在最高四分位数的人群中，风险增加62% (ORQ4vsQ1=1.62, CI = 1.03-2.54；p-trend = 0.02)。全氟辛烷磺酸（PFOS）与风险增加相关（ORperlog2=1.47, CI = 1.05-2.06），无四分位数趋势（p-trend = 0.79）。全氟壬烷酸（ORperlog2=1.36, CI = 0.95-1.95）和全氟癸酸（ORperlog2=1.35, CI = 0.94-1.95）之间存在非单调四分位数趋势（p-trend = 0.12-0.21）。MeFOSAA相关性在55-59岁女性中最强（ORperlog2=1.60, CI = 1.13-2.27），在60-64岁女性中较弱（ORperlog2=1.31, CI = 0.90-1.90），在65岁以上女性中为零(ORperlog2=1.02, CI = 0.73-1.43；p异质性= 0.22)。在采血后诊断≥8年的病例中，相关性持续存在。结论：这些发现为全氟辛烷磺酸作为卵巢癌危险因素提供了新的证据，特别是全氟辛烷磺酸和全氟辛烷磺酸前体MeFOSAA。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

JNCI Journal of the National Cancer Institute 医学-肿瘤学

CiteScore

17.00

自引率

2.90%

发文量

203

审稿时长

4-8 weeks

期刊介绍： The Journal of the National Cancer Institute is a reputable publication that undergoes a peer-review process. It is available in both print (ISSN: 0027-8874) and online (ISSN: 1460-2105) formats, with 12 issues released annually. The journal's primary aim is to disseminate innovative and important discoveries in the field of cancer research, with specific emphasis on clinical, epidemiologic, behavioral, and health outcomes studies. Authors are encouraged to submit reviews, minireviews, and commentaries. The journal ensures that submitted manuscripts undergo a rigorous and expedited review to publish scientifically and medically significant findings in a timely manner.