Faculté de Médecine, Institut National de la Santé et de la Recherche Médicale U625, Guadeloupe, French West Indies.
J Clin Oncol. 2010 Jul 20;28(21):3457-62. doi: 10.1200/JCO.2009.27.2153. Epub 2010 Jun 21.
Determining whether environmental estrogens are associated with the risk of prostate cancer may have important implications for our general understanding of this disease. The estrogenic insecticide chlordecone was used extensively in the French West Indies, contaminating the population for more than 30 years. We analyzed the relationship between exposure to chlordecone and the risk of prostate cancer.
We investigated 623 men with prostate cancer and 671 controls. Exposure was analyzed according to case-control status, using either current plasma concentration or a cumulative exposure index based on years of exposure. We genotyped two single-nucleotide polymorphisms (rs3829125 and rs17134592) in the gene encoding chlordecone reductase.
We found a significant increase in the risk of prostate cancer with increasing plasma chlordecone concentration (odds ratio [OR], 1.77; 95% CI, 1.21 to 2.58 for the highest tertile of values above the limit of detection [LD]; P trend = .002) and for cumulative exposure index (OR, 1.73; 95% CI, 1.04 to 2.88 for the highest quartile; P trend = .004). Stronger associations were observed among those with a positive family history of prostate cancer and among those who had lived in a Western country. The rs3829125 and rs17134592 allele variants were in complete linkage disequilibrium and were found at low frequency (0.04). Among subjects with plasma chlordecone concentrations above the LD, carriers of the allele variants had a higher risk of prostate cancer (OR, 5.23; 95% CI, 0.82 to 33.32).
These findings support the hypothesis that exposure to environmental estrogens increases the risk of prostate cancer.
确定环境雌激素是否与前列腺癌的风险相关,可能对我们对这种疾病的普遍认识具有重要意义。曾在法属西印度群岛广泛使用的雌激素杀虫剂氯丹,污染了当地人群长达 30 多年。我们分析了氯丹暴露与前列腺癌风险之间的关系。
我们调查了 623 名前列腺癌患者和 671 名对照者。根据病例对照的情况,利用当前的血浆浓度或基于暴露年限的累积暴露指数分析了暴露情况。我们对编码氯丹还原酶的基因中的两个单核苷酸多态性(rs3829125 和 rs17134592)进行了基因分型。
我们发现,随着血浆氯丹浓度的升高,前列腺癌的风险呈显著增加趋势(最高三分位值以上的比值比[OR],1.77;95%可信区间[CI],1.21 至 2.58;P 趋势=.002),且累积暴露指数也呈增加趋势(最高四分位值的 OR,1.73;95%CI,1.04 至 2.88;P 趋势=.004)。在有阳性前列腺癌家族史的人群和居住在西方国家的人群中,观察到的相关性更强。rs3829125 和 rs17134592 等位基因变异体完全连锁不平衡,且出现频率较低(0.04)。在血浆氯丹浓度高于检测限的人群中,携带等位基因变异体的个体前列腺癌风险更高(OR,5.23;95%CI,0.82 至 33.32)。
这些发现支持了环境雌激素暴露会增加前列腺癌风险的假说。