Jones Rena R, Madrigal Jessica M, Medgyesi Danielle N, Fisher Jared A, Calafat Antonia M, Botelho Julianne Cook, Kato Kayoko, Albert Paul S, Silverman Debra T, Hofmann Jonathan N, Trabert Britton
Occupational & Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, United States.
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, United States.
J Natl Cancer Inst. 2025 Nov 1;117(11):2272-2279. doi: 10.1093/jnci/djaf204.
Perfluoroalkyl 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.
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 US study centers (1993-2001). We looked at cases through 2016 and quantitated 8 PFAS in prediagnostic serum samples. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for continuous (log2-transformed) and categorized PFAS concentrations by using conditional logistic regression models, implicitly adjusting for matching factors (age, center, year of random assignment, year of blood draw, race and ethnicity) and adjusting for smoking, body mass index, family history of cancer, menopausal hormone therapy and oral contraceptive use, parity, and number of freeze-thaw cycles.
We found a positive association with ovarian cancer for a doubling in 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA) concentrations (OR for log2 = 1.24, 95% CI = 1.03 to 1.49) and 62% greater risk among those in the highest quartile (OR for quartile 4 vs quartile 1 = 1.62, 95% CI = 1.03 to 2.54; P for trend = .02). Perfluorooctane sulfonic acid (PFOS) was associated with increased risk (OR for log2 = 1.47, 95% CI = 1.05 to 2.06), with no quartile trend (P for trend = .79). Associations with perfluorononanoic acid (OR for log2 = 1.36, 95% CI = 0.95 to 1.95) and perfluorodecanoic acid (OR for log2 = 1.35, 95% CI = 0.94 to 1.95) were suggested, with nonmonotonic quartile trends (P for trend = .12 to .21). The MeFOSAA associations were strongest in women aged 55-59 years (OR for log 2 = 1.60, 95% CI = 1.13 to 2.27), more moderate in women aged 60-64 years (OR for log2 = 1.31, 95% CI = 0.90 to 1.90), and null among women 65 years of age and older (OR for log2 = 1.02, 95% CI = 0.73 to 1.43; P for heterogeneity = .22). Associations persisted in cases diagnosed 8 years or more after blood collection.
These findings offer novel evidence for PFAS as ovarian cancer risk factors, particularly PFOS and MeFOSAA, a PFOS precursor.
全氟烷基和多氟烷基物质（PFAS）是持久性、广泛存在的环境污染物，其中一些具有内分泌干扰特性。关于妇科癌症的研究有限；我们评估了卵巢癌，这是一种罕见且往往致命的恶性肿瘤。
这项巢式病例对照研究纳入了前列腺、肺、结肠直肠癌和卵巢癌筛查试验中的318例卵巢癌病例和472例个体匹配的女性对照，该试验从美国10个研究中心招募了年龄在55 - 74岁的参与者（始于1993年，结束于2001年）。我们观察病例至2016年，并对诊断前血清样本中的8种PFAS进行定量分析。我们使用条件逻辑回归模型估计连续（对数2转换）和分类PFAS浓度的比值比（OR）和95%置信区间（CI），隐含地调整匹配因素（年龄、中心、随机分组年份、采血年份、种族和民族），并调整吸烟、体重指数、癌症家族史、绝经激素治疗和口服避孕药使用情况、产次以及冻融循环次数。
我们发现2 - （N - 甲基 - 全氟辛烷磺酰胺基）乙酸（MeFOSAA）浓度翻倍与卵巢癌呈正相关（对数2的OR = 1.24，95% CI = 1.03至1.49），且最高四分位数人群的风险高62%（四分位数4与四分位数1的OR = 1.62，95% CI = 1.03至2.54；趋势P值 = 0.02）。全氟辛烷磺酸（PFOS）与风险增加相关（对数2的OR = 1.47，95% CI = 1.05至2.06），无四分位数趋势（趋势P值 = 0.79）。提示与全氟壬酸（对数2的OR = 1.36，95% CI = 0.95至1.95）和全氟癸酸（对数2的OR = 1.35，95% CI = 0.94至1.95）有关联，具有非单调的四分位数趋势（趋势P值 = 0.12至0.21）。MeFOSAA的关联在55 - 59岁女性中最强（对数2的OR = 1.60，95% CI = 1.13至2.27），在60 - 64岁女性中较为中等（对数2的OR = 1.31，95% CI = 0.90至1.90），在65岁及以上女性中无关联（对数2的OR =
