邻苯二甲酸酯与乳腺癌关系的病例对照研究

Relationships between phthalic acid esters and breast cancer in a case-control study

[目的]了解乳腺癌患者与健康人群血液中邻苯二甲酸酯(PAEs)的暴露水平,探究PAEs与乳腺癌的关系。[方法]在2015年10月—2016年12月,采用病例对照研究方法,在哈尔滨医科大学附属第二医院招募乳腺癌患者和健康人群各60名作为调查对象,进行问卷调查、体格检查。问卷调查内容包括性别、年龄、月经初潮的年龄、吸烟饮酒习惯、受教育程度、体育锻炼情况、哺乳时间等。由专业医务人员对调查对象进行身高、体重以及血压的测量,并计算其体质量指数(BMI)。采用气相色谱-质谱联用仪(GC-MS)对调查人群血清中15种PAEs的含量进行测定,用电化学发光法检测乳腺癌血清学特异性指标糖类抗原(CA)153的含量。采用Spearman秩相关分析PAEs与CA153的关联,采用logistic回归分析乳腺癌患病的危险因素。[结果]120名调查对象中,乳腺癌组与对照组月经初潮年龄的差异有统计学意义(P<0.05),而BMI、舒张压、收缩压、文化程度、婚姻状况、体育锻炼情况、饮酒吸烟习惯、哺乳时间的差异无统计学意义(均P>0.05)。调查对象血液中邻苯二甲酸二异丁酯(DIBP)、邻苯二甲酸二丁酯(DBP)、邻苯二甲酸二环己酯(DCHP)、邻苯二甲酸二(2-乙基己)酯(DEHP)、邻苯二甲酸二乙酯(DEP)、邻苯二甲酸二甲氧基乙酯(DMEP)、邻苯二甲酸二(4-甲基-2-戊基)酯(BMPP)、邻苯二甲酸二(2-乙氧基)乙酯(DEEP)、邻苯二甲酸二戊酯(DPP)的检出率均高于80%。Spearman相关分析显示,DEP、DIBP、DBP、DMEP、DPP、DEHP与CA153水平呈正相关关系(r分别为0.282、0.581、0.664、0.632、0.499、0.597,均P<0.05)。多因素logistics回归结果表明,DIBP、DBP、DMEP、DPP、DEHP为乳腺癌患病的危险因素(OR分别为2.356、5.253、1.126、1.879、2.217,均P<0.05)。[结论]PAEs暴露可能会增加乳腺癌发生的风险。

[Objective] To detect the exposure levels of phthalic acid esters （PAEs） in the blood of breast cancer patients and healthy subjects, and explore the relationships between PAEs and breast cancer.[Methods] From October 2015 to December 2016, based on a case-control study in the Second Affiliated Hospital of Harbin Medical University, 60 breast cancer patients and 60 healthy subjects were recruited and investigated by questionnaire survey and physical examination. The questionnaire included gender, age, age of menarche, habits of smoking and drinking, education level, physical exercise, and lactation time. The physical examination was carried out by professional medical staff to measure the height, weight, and blood pressure of the study subjects and to calculate body mass index （BMI）. The levels of 15 PAEs and carbohydrate antigen （CA） 153 （a serological specific index of breast cancer） in serum were detected by gas chromatography-mass spectrometry and electrochemiluminescence, respectively. Spearman rank correlation analysis was used to analyze the correlation between PAEs and CA153, and logistic regression was used to analyze the risk factors of breast cancer.[Results] For all 120 subjects, the differences of BMI, diastolic blood pressure, systolic blood pressure, education level, marital status, physical exercise status, drinking habit, smoking habit, and lactation time were not statistically significant between the breast cancer group and the control group （Ps 〉 0.05）, except the menarche age （P 〈 0.05）. The positive rates of diisobutyl phthalate （DIBP）, dibutylphthalate （DBP）, dicyclohexyl phthalate （DCHP）, di-2-ethylhexyl phthalate （DEHP）, diethyl phthalate （DEP）, dimethoxyethylphthalate （DMEP）, bis（4-methyl-2-pentyl） phthalate （BMPP）, bis（2-ethoxyethyl） phthalate （DEEP）, and dipenyl phthalate （DPP） were all higher than 80% in the study subjects. The Spearman rank correlation analysis results showed that CA153 was positively correlated with DEP, DIBP, DBP, DMEP, DPP, and DEHP （r=0.282, 0.581, 0.664, 0.632, 0.499, and 0.597, respectively, Ps 〈 0.05）. The multiple logistic regression analysis results showed that DIBP, DBP, DMEP, DPP, and DEHP were the risk factors of breast cancer （OR=2.356, 5.253, 1.126, 1.879, and 2.217, respectively, Ps 〈 0.05）.[Conclusion] Exposure to PAEs might increase the risk of breast cancer.