Perfluorinated compounds are related to breast cancer risk in Greenlandic Inuit: a case control study.
Perfluorinated compounds are related to breast cancer risk in Greenlandic Inuit: a case control study.
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DOI：
10.1186/1476-069x-10-88
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发表时间：
2011-10-06
期刊：
影响因子：
--
通讯作者：
Dewailly E
中科院分区：
文献类型：
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作者：
Bonefeld-Jorgensen EC;Long M;Bossi R;Ayotte P;Asmund G;Krüger T;Ghisari M;Mulvad G;Kern P;Nzulumiki P;Dewailly E
乳腺癌(BC)是西方世界女性最常见的癌症。在极少数情况下，格陵兰和加拿大的因纽特人的卑诗省人口显著增加，尽管仍低于西部人口。先前的数据表明，接触持久性有机污染物(POP)可能会增加BC的风险。大鼠研究表明，全氟化合物(PFCs)会显著增加乳腺纤维腺瘤的发病率。本研究旨在评估格陵兰因纽特BC患者血清POPS/PFC水平与其对照组之间的关系，以及联合POP对核激素受体的影响是否影响BC的风险。在2000-2003年间，从格陵兰岛不同地区抽取了31例BC病例和115名对照。测定血清POPs、PFC、某些金属的水平，以及血清POP相关因素对雌激素(ER)、雄激素(AR)和AH受体(AhR)反式活性的影响。用独立学生t检验比较差异，用非条件Logistic回归模型估计优势比。我们首次观察到血清PFC水平与BC风险之间存在显著的相关性。BC病例还显示，在最高四分位数处的多氯联苯浓度显著较高。此外，还发现联合血清POP诱导的激动型AR反式活性与BC风险显著相关，并且病例引发显著POP相关激素样激动型ER反式活性的样本频率更高。在案例中，AhR的毒性当量最低。血清POPs水平，尤其是PFC水平可能是因纽特人BC发生的危险因素。血清中与POP相关的异种雌激素和异种雄激素联合作用所造成的激素紊乱可能会增加因纽特人患乳腺癌的风险。需要进一步的调查来记录这些研究结论。
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.