眾所周知，干擾內(nèi)分泌的化學(xué)物質(zhì)可能增加女性乳腺癌發(fā)生風(fēng)險(xiǎn)。表面活性劑被廣泛用于肥皂、洗衣粉、洗衣液、洗潔精、洗手液、洗發(fā)水、護(hù)發(fā)素、沐浴露、洗面奶、潤(rùn)膚乳等日用化學(xué)品，全氟辛烷磺酸和全氟辛酸是其中兩種污染環(huán)境且干擾內(nèi)分泌的全氟烷化物，并被懷疑普遍存在于全世界人群血液。
2019年5月3日，國(guó)際癌癥聯(lián)盟《國(guó)際癌癥雜志》在線發(fā)表法國(guó)巴黎第十一大學(xué)、古斯塔夫魯西研究所、法國(guó)農(nóng)業(yè)科學(xué)研究院食品殘留物污染物研究實(shí)驗(yàn)室、喬治弗朗索瓦勒克萊爾癌癥中心科多爾省女性腫瘤登記中心的法國(guó)國(guó)家教育部女性流行病學(xué)研究（E3N）報(bào)告，該研究人群由98995例出生于1925～1950年并從1990年開(kāi)始隨訪的法國(guó)女性組成，利用該研究人群的女性血液標(biāo)本，法國(guó)調(diào)查了全氟辛烷磺酸和全氟辛酸血液濃度與女性乳腺癌發(fā)生風(fēng)險(xiǎn)的相關(guān)性。
該法國(guó)女性人群嵌套病例對(duì)照研究對(duì)無(wú)職業(yè)接觸史的194例乳腺癌絕經(jīng)后患者和194例無(wú)乳腺癌對(duì)照者血液標(biāo)本進(jìn)行分析，通過(guò)液相色譜質(zhì)譜聯(lián)用測(cè)定全氟辛烷磺酸和全氟辛酸的血清濃度，通過(guò)條件邏輯回歸模型，校正血脂、體重指數(shù)、吸煙史、體力活動(dòng)、學(xué)歷、良性乳腺病史、乳腺癌家族史、生育史、哺乳史、月經(jīng)史、口服避孕藥史、絕經(jīng)后激素補(bǔ)充史、飲食評(píng)分、采血時(shí)年齡、采血時(shí)體重指數(shù)、采血時(shí)絕經(jīng)狀態(tài)、采血時(shí)年份等其他因素的影響，將全氟辛烷磺酸、全氟辛酸的血清濃度四等分，推算乳腺癌風(fēng)險(xiǎn)的比值比和95%置信區(qū)間，所有統(tǒng)計(jì)學(xué)檢驗(yàn)均為雙側(cè)。
結(jié)果，雖然全氟烷化物濃度與不分類型的乳腺癌風(fēng)險(xiǎn)無(wú)顯著相關(guān)性，但是全氟辛烷磺酸濃度與雌激素受體陽(yáng)性、孕激素受體陽(yáng)性乳腺癌風(fēng)險(xiǎn)成正比，全氟辛烷磺酸濃度次高、最高四分之一（17.3～22.5、22.5～85.3 ng/mL）的患者與最低四分之一（5.8～13.6 ng/mL）的患者和對(duì)照者相比：
雌激素受體陽(yáng)性乳腺癌風(fēng)險(xiǎn)高2.22、2.33倍（95%置信區(qū)間：1.05～4.69、1.11～4.90，趨勢(shì)分析P=0.04）
孕激素受體陽(yáng)性乳腺癌風(fēng)險(xiǎn)高2.47、2.76倍（95%置信區(qū)間：1.07～5.65、1.21～6.30，趨勢(shì)分析P=0.02）
對(duì)于激素受體陰性乳腺癌，僅全氟辛烷磺酸濃度次低四分之一與最低四分之一的患者和對(duì)照者相比：
雌激素受體陰性乳腺癌風(fēng)險(xiǎn)高15.4倍（95%置信區(qū)間：1.84～129.19，趨勢(shì)分析P=0.72）
孕激素受體陰性乳腺癌風(fēng)險(xiǎn)高3.47倍（95%置信區(qū)間：1.29～9.15，趨勢(shì)分析P=0.93）
雖然全氟辛酸與激素受體陽(yáng)性乳腺癌風(fēng)險(xiǎn)無(wú)顯著相關(guān)性，但是全氟辛酸次低四分之一（4.8～6.8 ng/mL）與最低四分之一（1.3～4.8 ng/mL）的患者和對(duì)照者相比：
雌激素受體陰性乳腺癌風(fēng)險(xiǎn)高7.73倍（95%置信區(qū)間：1.46～41.08，趨勢(shì)分析P=0.59）
孕激素受體陰性乳腺癌風(fēng)險(xiǎn)高3.44倍（95%置信區(qū)間：1.30～9.10，趨勢(shì)分析P=0.90）
因此，該研究結(jié)果表明，不同全氟烷化物的血液濃度與不同乳腺癌的風(fēng)險(xiǎn)存在顯著相關(guān)性。雖然全氟辛烷磺酸濃度與激素受體陽(yáng)性乳腺癌存在顯著線性劑量效應(yīng)相關(guān)性，但是僅低濃度的全氟辛烷磺酸和全氟辛酸與激素受體陰性乳腺癌存在顯著相關(guān)性。該研究結(jié)果突顯了將全氟烷化物接觸量作為乳腺癌潛在風(fēng)險(xiǎn)因素的重要性。由于接觸干擾內(nèi)分泌的化學(xué)物質(zhì)應(yīng)被視為乳腺癌潛在風(fēng)險(xiǎn)因素，故為重大公共衛(wèi)生問(wèn)題。
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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