Veronique-Baudin Jacqueline, Dieye Moustapha, Kouyoumdjian Jean-Claude, Vacheron Francis, Draganescu Cyprian, Azaloux Hervé
Registre des Cancers de la Martinique, AMREC, Le Lamentin, France.
Prog Urol. 2006 Jun;16(3):303-10.
The proliferation of prostate cells appears to be influenced by two steroidal hormones: testosterone and vitamin D, whose action appears to mediated by their respective receptors. The genes coding for these two receptors and the gene coding for 5-alpha-reductase (enzyme involved in testosterone metabolism) have been identified as candidate genes for prostate cancer predisposition. Previous epidemiological and genetic susceptibility studies have reported controversial results concerning the role of these genes on prostate cancer incidence in various populations. The objective of this study was to determine the possible association in this population between polymorphisms of these genes, and the clinical and pathological stage and grade of prostate cancer.
This case-control epidemiogenetic study was based on 253 subjects living in Martinique. Prostate cancer is the most frequent cancer in men and the leading cause of cancer death in Martinique. Its incidence is 80 per 100,000 inhabitants (world population standardized rates), which makes Martinique one of the most severely affected regions in the world with an incidence close to that of Afro-Americans. Cases and controls were recruitedfrom the hospital and general populations. The following gene polymorphisms were evaluated: the androgen receptor (AR) was studied by microsatellites of the CAG codon repeat domain; the vitamin D receptor (VDR) gene was studied on poly(A) sequences of the 3'-UTR region; 5a-reductase II (SRD5A2) was studied by poly(TA) microsatellites. The odds-ratio (OR) was estimated by logistic regression with integration of clinical and biological parameters.
Our results for the androgen receptor showed an association between the presence of more than 20 CAG repeats and localized or low-grade forms. A risk related to the heavy allele of VDR was observed in advanced and low-grade forms (PSA-T > 20 ng/ml). Lastly, no 5a-reductase polymorphism distinguishing cases from controls was observed.
This study demonstrated results that differ from those observed for other populations with a similar ethnic origin. For AR and VDR genes, the presence of a heavy allele is associated with an increased risk of developing prostate cancer with a poor prognosis. No high-risk group was identified according to 5a-reductase gene polymorphism.
前列腺细胞的增殖似乎受两种甾体激素影响：睾酮和维生素D，它们的作用似乎由各自的受体介导。编码这两种受体的基因以及编码5-α-还原酶（参与睾酮代谢的酶）的基因已被确定为前列腺癌易感性的候选基因。先前的流行病学和遗传易感性研究报告了这些基因在不同人群中对前列腺癌发病率的作用存在相互矛盾的结果。本研究的目的是确定该人群中这些基因的多态性与前列腺癌的临床和病理分期及分级之间可能存在的关联。
本病例对照遗传流行病学研究基于253名生活在马提尼克岛的受试者。前列腺癌是男性中最常见的癌症，也是马提尼克岛癌症死亡的主要原因。其发病率为每10万居民80例（世界人口标准化率），这使马提尼克岛成为世界上受影响最严重的地区之一，发病率接近非裔美国人。病例和对照从医院和普通人群中招募。评估了以下基因多态性：通过CAG密码子重复结构域的微卫星研究雄激素受体（AR）；通过3'-UTR区域的聚（A）序列研究维生素D受体（VDR）基因；通过聚（TA）微卫星研究5α-还原酶II（SRD5A2）。通过逻辑回归并整合临床和生物学参数来估计优势比（OR）。
我们关于雄激素受体的研究结果显示，CAG重复序列超过20个与局限性或低级别形式之间存在关联。在晚期和低级别形式（PSA-T>20 ng/ml）中观察到与VDR重等位基因相关的风险。最后，未观察到区分病例与对照的5α-还原酶多态性。
本研究显示的结果与其他具有相似种族背景的人群中观察到的结果不同。对于AR和VDR基因，重等位基因的存在与前列腺癌预后不良的发病风险增加相关。根据5α-还原酶基因多态性未鉴定出高危组。
