CDKN1A and CDKN1B polymorphisms and risk of advanced prostate carcinoma.
CDKN1A and CDKN1B polymorphisms and risk of advanced prostate carcinoma.
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发表时间：
2003-05
期刊：
影响因子：
11.2
通讯作者：
A. Kibel;B. Suarez;Jay S. Belani;Joe Oh;R. Webster;Michele Brophy-Ebbers;Chan Guo;W. Catalona;J. Picus;P. Goodfellow
中科院分区：
文献类型：
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作者：
A. Kibel;B. Suarez;Jay S. Belani;Joe Oh;R. Webster;Michele Brophy-Ebbers;Chan Guo;W. Catalona;J. Picus;P. Goodfellow
已经提出了前列腺癌易感性的多基因模型，其中常见的基因多态性变异（例如雄激素和维生素 D 受体）有助于肿瘤发生。导致前列腺癌风险的其他遗传因素的发现应该为检测和治疗这种常见恶性肿瘤的新方法提供机会。在此，我们检查了 CDKN1A (p21(cip1)) 3'-非翻译区和 CDKN1B (p27(kip1)) 密码子 109 中的单核苷酸多态性变异与欧美人群中晚期前列腺癌的关联。使用 PCR 扩增和限制性消化测定法对 96 例病例和 106 例对照进行了分析。根据消化产物，CDKN1A 基因型分为 CC、CT 和 TT。与 CC 基因型相比，CDKN1A 基因型 CT 和 TT 与晚期前列腺癌风险增加相关[优势比 (OR)，2.24； 95% 置信区间 (CI)，1.02-4.95]。同样根据消化产物，CDKN1B 基因型被评分为 VV、VG 或 GG。 CDKN1B 基因型 VV 还与晚期前列腺癌风险增加相关（OR，1.95；95% CI，1.09-3.47）。这些关联在患有雄激素非依赖性疾病的患者中尤其强烈[对于CDKN1A和CDKN1B高风险基因型，OR分别为2.88（95% CI，1.19-6.97）和2.11（95% CI，1.05-4.22）]。此外，在中位诊断年龄以下的患者队列中，CDKN1B 的相关性特别强（OR，2.23；95% CI，1.08-4.59）。这些结果表明，在欧美人群中，CDKN1A 和 CDKN1B 变异与晚期前列腺癌相关。 CDKN1A 和/或 CDKN1B 基因型的分析可能有助于确定哪些患者有患晚期前列腺癌的风险，因此可以从积极的筛查、预防和/或治疗中获得最大收益。
A multigenic model of prostate cancer susceptibility has been proposed, in which common polymorphic variants of genes, such as the androgen and vitamin D receptor, contribute to tumorigenesis. The discovery of additional genetic factors that contribute to prostate cancer risk should provide opportunities for new approaches to the detection and treatment of this common malignancy. Herein, we examined single nucleotide polymorphic variants in the 3'-untranslated region of CDKN1A (p21(cip1)) and in codon 109 of CDKN1B (p27(kip1)) for association with advanced prostate cancer in a European-American population. Ninety-six cases and 106 controls were analyzed using PCR amplification and restriction digestion assays. CDKN1A genotype was scored as CC, CT, and TT on the basis of the digestion products. The CDKN1A genotypes CT and TT were associated with an increased risk of advanced prostate carcinoma compared with the CC genotype [odds ratio (OR), 2.24; 95% confidence interval (CI), 1.02-4.95]. The CDKN1B genotype was scored as VV, VG, or GG, again on the basis of the digestion products. The CDKN1B genotype VV was also associated with an increased risk of advanced prostate carcinoma (OR, 1.95; 95% CI, 1.09-3.47). These associations were particularly strong in those patients with androgen-independent disease [OR = 2.88 (95% CI, 1.19-6.97) and 2.11 (95% CI, 1.05-4.22) for high-risk genotypes of CDKN1A and CDKN1B, respectively]. In addition, the association of CDKN1B was particularly strong in the cohort of patients under the median age of diagnosis (OR, 2.23; 95% CI, 1.08-4.59). These results suggest that in a European-American population, CDKN1A and CDKN1B variants are associated with advanced prostate cancer. Analysis of CDKN1A and/or CDKN1B genotypes may prove useful in determining which patients are at risk for developing advanced prostate carcinoma and therefore would gain the most from aggressive screening, prophylaxis, and/or treatment.