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众所周知，干扰内分泌的化学物质可能增加女性乳腺癌发生风险。表面活性剂被广泛用于肥皂、洗衣粉、洗衣液、洗洁精、洗手液、洗发水、护发素、沐浴露、洗面奶、润肤乳等日用化学品，全氟辛烷磺酸和全氟辛酸是其中两种污染环境且干扰内分泌的全氟烷化物，并被怀疑普遍存在于全世界人群血液。 2019年5月3日，国际癌症联盟《国际癌症杂志》在线发表法国巴黎第十一大学、古斯塔夫鲁西研究所、法国农业科学研究院食品残留物污染物研究实验室、乔治弗朗索瓦勒克莱尔癌症中心科多尔省女性肿瘤登记中心的法国国家教育部女性流行病学研究（E3N）报告，该研究人群由98995例出生于1925～1950年并从1990年开始随访的法国女性组成，利用该研究人群的女性血液标本，法国调查了全氟辛烷磺酸和全氟辛酸血液浓度与女性乳腺癌发生风险的相关性。 该法国女性人群嵌套病例对照研究对无职业接触史的194例乳腺癌绝经后患者和194例无乳腺癌对照者血液标本进行分析，通过液相色谱质谱联用测定全氟辛烷磺酸和全氟辛酸的血清浓度，通过条件逻辑回归模型，校正血脂、体重指数、吸烟史、体力活动、学历、良性乳腺病史、乳腺癌家族史、生育史、哺乳史、月经史、口服避孕药史、绝经后激素补充史、饮食评分、采血时年龄、采血时体重指数、采血时绝经状态、采血时年份等其他因素的影响，将全氟辛烷磺酸、全氟辛酸的血清浓度四等分，推算乳腺癌风险的比值比和95%置信区间，所有统计学检验均为双侧。 结果，虽然全氟烷化物浓度与不分类型的乳腺癌风险无显著相关性，但是全氟辛烷磺酸浓度与雌激素受体阳性、孕激素受体阳性乳腺癌风险成正比，全氟辛烷磺酸浓度次高、最高四分之一（17.3～22.5、22.5～85.3 ng/mL）的患者与最低四分之一（5.8～13.6 ng/mL）的患者和对照者相比：
对于激素受体阴性乳腺癌，仅全氟辛烷磺酸浓度次低四分之一与最低四分之一的患者和对照者相比：
虽然全氟辛酸与激素受体阳性乳腺癌风险无显著相关性，但是全氟辛酸次低四分之一（4.8～6.8 ng/mL）与最低四分之一（1.3～4.8 ng/mL）的患者和对照者相比：
因此，该研究结果表明，不同全氟烷化物的血液浓度与不同乳腺癌的风险存在显著相关性。虽然全氟辛烷磺酸浓度与激素受体阳性乳腺癌存在显著线性剂量效应相关性，但是仅低浓度的全氟辛烷磺酸和全氟辛酸与激素受体阴性乳腺癌存在显著相关性。该研究结果突显了将全氟烷化物接触量作为乳腺癌潜在风险因素的重要性。由于接触干扰内分泌的化学物质应被视为乳腺癌潜在风险因素，故为重大公共卫生问题。 Int J Cancer. 2019 May 3. [Epub ahead of print] Perfluorinated alkylated substances serum concentration and breast cancer risk: Evidence from a nested case-control study in the French E3N cohort. Mancini FR, Cano-Sancho G, Gambaretti J, Marchand P, Boutron-Ruault MC, Severi G, Arveux P, Antignac JP, Kvaskoff M. Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France; Gustave Roussy, Villejuif, France; UMR INRA-Oniris 1329 LABERCA, Nantes, France; Breast and Gynaecologic Cancer Registry of Cote d'Or, Georges-Francois Leclerc Cancer Centre, UNICANCER, Dijon, France. WHAT'S NEW? Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are two environmental endocrine-disrupting chemicals suspected to be ubiquitously present in the blood of the human population. This nested case-control study including non-occupationally exposed postmenopausal French women suggests a linear dose-response relationship between PFOS serum concentrations and the risk of developing hormone receptor-positive breast cancer. Furthermore, an increased risk of developing ER- and PR- tumors is associated to middle-low serum concentrations of PFOA and PFOS. Exposure to endocrine-disrupting chemicals should be considered as a potential risk factor for breast cancer, thus a serious public health issue. Endocrine-disrupting chemicals are proposed to increase breast cancer (BC) incidence. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), two perfluorinated alkylated substances (PFASs), are suspected to be ubiquitously present in the blood of human population worldwide. We investigated the associations between serum concentrations of these substances and BC risk. Etude Epidémiologique auprès de femmes de l'Education Nationale is a cohort of 98,995 French women born in 1925-1950 and followed up since 1990. We sampled 194 BC cases and 194 controls from women with available blood samples. Serum concentrations of PFASs were measured by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Adjusted conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two sided. While PFASs concentrations were not associated with BC risk overall, we found positively linear associations between PFOS concentrations and the risk of ER+ (3rd quartile: OR = 2.22 [CI = 1.05-4.69]; 4th quartile: OR = 2.33 [CI = 1.11-4.90]); Ptrend = 0.04) and PR+ tumors (3rd quartile: OR = 2.47 [CI = 1.07-5.65]; 4th quartile: OR = 2.76 [CI = 1.21-6.30]; Ptrend = 0.02). When considering receptor-negative tumors, only the 2nd quartile of PFOS was associated with risk (ER-: OR = 15.40 [CI = 1.84-129.19]; PR-: OR = 3.47 [CI = 1.29-9.15]). While there was no association between PFOA and receptor-positive BC risk, the 2nd quartile of PFOA was positively associated with the risk of receptor-negative tumors (ER-: OR = 7.73 [CI = 1.46-41.08]; PR-: OR = 3.44 [CI = 1.30-9.10]). PFAS circulating levels were differentially associated with BC risk. While PFOS concentration was linearly associated with receptor-positive tumors, only low concentrations of PFOS and PFOA were associated with receptor-negative tumors. Our findings highlight the importance of considering exposure to PFASs as a potential risk factor for BC. KEYWORDS: E3N cohort; Perfluorooctane sulfonate (PFOS); breast cancer; nested case-control study; perfluorooctanoic acid (PFOA); serum levels PMID: 31008526 DOI: 10.1002/ijc.32357
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