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日本人群中V89L SRD5A2基因多态性与前列腺癌发生的关联

Association of V89L SRD5A2 polymorphism with prostate cancer development in a Japanese population.

作者信息

Li Zhenhua, Habuchi Tomonori, Mitsumori Kenji, Kamoto Toshiyuki, Kinoshitu Hidefumi, Segawa Takehiko, Ogawa Osamu, Kato Tetsuro

机构信息

Department of Urology, Akita University School of Medicine, Akita, Japan.

出版信息

J Urol. 2003 Jun;169(6):2378-81. doi: 10.1097/01.ju.0000056152.57018.31.

Abstract

PURPOSE

The SRD5A2 gene codes the steroid 5-reductase type II, a critical mediator of androgen action, and the V89L and A49T polymorphisms of this gene may be associated with a distinct enzyme activity. We explored the association among these polymorphisms and the risk of prostate cancer or benign prostatic hyperplasia (BPH) in a Japanese population.

MATERIALS AND METHODS

This study included 302 patients with prostate cancer, 228 with BPH and 243 male controls. V89L and A49T polymorphisms were analyzed by the polymerase chain reaction restriction fragment length polymorphism method. Genotypes were evaluated by electrophoresis on agarose gel.

RESULTS

For the V89L polymorphism there were no significant differences in genotype frequencies in patients with prostate cancer and controls (p = 0.071) or in patients with BPH and male controls (p = 0.219). However, males with the VV or VL genotype were at significantly increased risk for prostate cancer compared with those with the LL genotype (adjusted OR 1.69, 95% CI 1.07 to 2.65, p = 0.024). The risk of BPH in males with the VV or VL genotype was not significantly elevated in comparison with those with the LL genotype (adjusted OR 1.37, 95% CI 0.85 to 2.20, p = 0.194). The V89L variant was not associated with the grade or stage of prostate cancer, or with patient age. For the A49T polymorphism all subjects had the AA genotype.

CONCLUSIONS

The V allele of the V89L polymorphism in the SRD5A2 gene may dominantly increase the risk of prostate cancer.

摘要

目的

SRD5A2基因编码II型类固醇5-还原酶,这是雄激素作用的关键介质,该基因的V89L和A49T多态性可能与不同的酶活性相关。我们在日本人群中探讨了这些多态性与前列腺癌或良性前列腺增生(BPH)风险之间的关联。

材料与方法

本研究纳入302例前列腺癌患者、228例BPH患者和243名男性对照。采用聚合酶链反应-限制性片段长度多态性方法分析V89L和A49T多态性。通过琼脂糖凝胶电泳评估基因型。

结果

对于V89L多态性,前列腺癌患者与对照之间(p = 0.071)或BPH患者与男性对照之间(p = 0.219)的基因型频率无显著差异。然而,与LL基因型男性相比,VV或VL基因型男性患前列腺癌的风险显著增加(校正OR 1.69,95%CI 1.07至2.65,p = 0.024)。与LL基因型男性相比,VV或VL基因型男性患BPH的风险未显著升高(校正OR 1.37,95%CI 0.85至2.20,p = 0.194)。V89L变异与前列腺癌的分级、分期或患者年龄无关。对于A49T多态性,所有受试者均为AA基因型。

结论

SRD5A2基因V89L多态性的V等位基因可能显著增加前列腺癌风险。

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