Krieger N, Wolff M S, Hiatt R A, Rivera M, Vogelman J, Orentreich N
Division of Research, Kaiser Foundation Research Institute, Oakland, Calif. 94611.
J Natl Cancer Inst. 1994 Apr 20;86(8):589-99. doi: 10.1093/jnci/86.8.589.
Five small case-control studies have examined the relationship between exposure to organochlorines and the risk of breast cancer and have found inconsistent results. In these studies, organochlorine levels in breast cancer patients were measured after (or at most 6 months before) diagnosis.
We tested the hypothesis that organochlorines are a risk factor for breast cancer, using prospectively gathered data on serum levels of DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] (the main metabolite of the pesticide DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane]) and polychlorinated biphenyls (PCBs).
Study subjects belonged to a cohort of 57,040 women (46,629 white, 8123 black, and 2288 Asian) from the San Francisco Bay Area who took a multiphasic health examination, independent of concern about risk of breast cancer, in the late 1960s. At that time, a sample of blood was obtained, then frozen and stored. Follow-up was through December 31, 1990. We conducted a nested case-control study of 150 case patients and 150 matched control subjects. A random sample of 50 women per racial/ethnic group who had been diagnosed with breast cancer more than 6 months after the multiphasic examination (mean follow-up = 14.2 years) was selected, and each case patient was matched to a cancer-free control subject.
Matched analyses found no differences in the case patients' and control subjects' serum levels of DDE (mean difference = 0.2 parts per billion [ppb]; 95% confidence interval [CI] = -6.7, 7.2) or PCBs (mean difference = -0.4 ppb; 95% CI = -0.8, 0.1). DDE levels, however, tended to be higher among black case patients compared with black controls (mean difference = 5.7 ppb; 95% CI = -3.3, 14.8), and PCBs were lower among white case patients compared with white controls (mean difference = -0.6 ppb; 95% CI = -1.2, -0.1). Organochlorine levels were significantly higher among black and Asian women compared with white women. The mean difference for DDE was 11.0 ppb for black women (95% CI = 4.3, 17.6) and 12.6 ppb for Asian women (95% CI = 6.0, 19.2); for PCBs, the respective differences were 0.8 ppb for black women (95% CI = 0.2, 1.4) and 1.4 ppb for Asian women (95% CI = 0.8, 1.9). The results were not altered by adjusting for relevant confounders, and the lack of association between exposure to organochlorines and breast cancer was present regardless of length of follow-up, year of diagnosis, or the case patient's menopausal and estrogen-receptor status.
The data do not support the hypothesis that exposure to DDE and PCBs increases risk of breast cancer.
Future investigations must consider the biologic mechanisms involved and variations in exposure to chemical pollutants and of breast cancer incidence rates among diverse groups of women.
五项小型病例对照研究探讨了有机氯暴露与乳腺癌风险之间的关系，结果并不一致。在这些研究中，乳腺癌患者的有机氯水平是在诊断后（或最多在诊断前6个月）测量的。
我们使用前瞻性收集的血清中DDE[1,1-二氯-2,2-双（对氯苯基）乙烯，农药DDT（2,2-双（对氯苯基）-1,1,1-三氯乙烷）的主要代谢产物]和多氯联苯（PCBs）水平的数据，检验有机氯是乳腺癌风险因素的假设。
研究对象来自旧金山湾区的57,040名女性队列（46,629名白人、8123名黑人、2288名亚洲人），她们在20世纪60年代末进行了多阶段健康检查，与对乳腺癌风险的担忧无关。当时采集了一份血液样本，然后冷冻保存。随访至1990年12月31日。我们对150例病例患者和150名匹配的对照对象进行了巢式病例对照研究。从每个种族/族裔组中随机抽取50名在多阶段检查后6个月以上被诊断为乳腺癌（平均随访时间=14.2年）的女性，每个病例患者与一名无癌对照对象匹配。
匹配分析发现，病例患者和对照对象的血清DDE水平（平均差异=0.2十亿分率[ppb]；95%置信区间[CI]=-6.7,7.2）或PCBs水平（平均差异=-0.4 ppb；95%CI=-0.8,0.1）没有差异。然而，与黑人对照相比，黑人病例患者的DDE水平往往更高（平均差异=5.7 ppb；9%CI=-3.3,14.8），与白人对照相比，白人病例患者的PCBs水平更低（平均差异=-0.6 ppb；95%CI=-1.2,-0.1）。黑人和亚洲女性的有机氯水平显著高于白人女性。黑人女性的DDE平均差异为11.0 ppb（95%CI=4.3,17.6），亚洲女性为12.6 ppb（95%CI=6.0,19.2）；对于PCBs，黑人女性的差异分别为0.8 ppb（95%CI=0.2,1.4），亚洲女性为1.4 ppb（95%CI=0.8,1.9）。调整相关混杂因素后结果未改变，无论随访时间长短、诊断年份以及病例患者的绝经和雌激素受体状态如何，有机氯暴露与乳腺癌之间均无关联。
数据不支持DDE和PCBs暴露会增加乳腺癌风险的假设。
未来的研究必须考虑所涉及的生物学机制以及不同女性群体中化学污染物暴露情况和乳腺癌发病率之间的差异。
