Centre for Arctic Environmental Medicine, Department of Public Health, Aarhus University, Denmark.
Environ Health. 2011 Oct 6;10:88. doi: 10.1186/1476-069X-10-88.
Breast cancer (BC) is the most common cancer for women in the western world. From very few cases an extraordinary increase in BC was observed in the Inuit population of Greenland and Canada although still lower than in western populations. Previous data suggest that exposure to persistent organic pollutants (POPs) might contribute to the risk of BC. Rat studies showed that perfluorinated compounds (PFCs) cause significantly increase in mammary fibroadenomas. This study aimed at evaluating the association between serum levels of POPs/PFCs in Greenlandic Inuit BC cases and their controls, and whether the combined POP related effect on nuclear hormone receptors affect BC risk.
Thirty-one BC cases and 115 controls were sampled during 2000-2003 from various Greenlandic districts. The serum levels of POPs, PFCs, some metals and the combined serum POP related effect on estrogen- (ER), androgen- (AR) and Ah-receptor (AhR) transactivity were determined. Independent student t-test was used to compare the differences and the odds ratios were estimated by unconditional logistic regression models.
We observed for the very first time a significant association between serum PFC levels and the risk of BC. The BC cases also showed a significantly higher concentration of polychlorinated biphenyls at the highest quartile. Also for the combined serum POP induced agonistic AR transactivity significant association to BC risk was found, and cases elicited a higher frequency of samples with significant POP related hormone-like agonistic ER transactivity. The AhR toxic equivalent was lowest in cases.
The level of serum POPs, particularly PFCs, might be risk factors in the development of BC in Inuit. Hormone disruption by the combined serum POP related xenoestrogenic and xenoandrogenic activities may contribute to the risk of developing breast cancer in Inuit. Further investigations are needed to document these study conclusions.
乳腺癌(BC)是西方国家女性最常见的癌症。尽管仍低于西方国家的水平,但在格陵兰和加拿大的因纽特人群中,BC 的病例却异常增加。先前的数据表明,接触持久性有机污染物(POPs)可能会增加患乳腺癌的风险。大鼠研究表明,全氟化合物(PFCs)会导致乳腺纤维腺瘤显著增加。本研究旨在评估格陵兰因纽特人乳腺癌病例及其对照者血清中 POPs/PFC 水平之间的关联,以及联合 POP 对核激素受体的相关影响是否会影响乳腺癌风险。
2000-2003 年,从格陵兰各地抽取了 31 名乳腺癌病例和 115 名对照者的血清样本。测定了 POPs、PFCs、一些金属的血清水平,以及联合 POP 对雌激素-(ER)、雄激素-(AR)和 Ah 受体(AhR)转录活性的相关影响。采用独立学生 t 检验比较差异,用非条件逻辑回归模型估计比值比。
我们首次观察到血清 PFC 水平与 BC 风险之间存在显著关联。BC 病例在最高四分位数时也表现出更高浓度的多氯联苯。联合血清 POP 诱导的 AR 转录活性的显著相关性也与 BC 风险有关,并且病例组中存在更多具有显著 POP 相关激素样激动性 ER 转录活性的样本。AhR 毒性当量在病例中最低。
血清中 POP 水平,特别是 PFCs,可能是因纽特人乳腺癌发展的危险因素。联合血清 POP 相关的外源性雌激素和雄激素活性对激素的破坏可能会增加因纽特人患乳腺癌的风险。需要进一步的研究来证实这些研究结论。