Association of the cyclin D1 gene G870A polymorphism with susceptibility to sporadic renal cell carcinoma.
Association of the cyclin D1 gene G870A polymorphism with susceptibility to sporadic renal cell carcinoma.
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DOI：
10.1097/01.ju.0000138156.24384.16
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发表时间：
2004-12
期刊：
影响因子：
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通讯作者：
Jiangang Yu;T. Habuchi;N. Tsuchiya;E. Nakamura;H. Kakinuma;Y. Horikawa;T. Inoue;O. Ogawa;Tetsuro Kato
中科院分区：
文献类型：
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作者：
Jiangang Yu;T. Habuchi;N. Tsuchiya;E. Nakamura;H. Kakinuma;Y. Horikawa;T. Inoue;O. Ogawa;Tetsuro Kato
目的细胞周期蛋白D1（CCND 1）mRNA选择性剪接产生2种转录本（转录本a和转录本b），这2种转录本可能受到外显子4保守剪接供体位点G870 A单核苷酸多态性的调控。先前的研究表明，CCND 1基因型与各种癌症的发展之间存在显着关联。我们探讨了该多态性与散发性肾细胞癌（RCC）的发病或病情之间的可能联系。材料与方法采用聚合酶链反应-限制性长度多态性分析方法，对191例肾细胞癌患者和400例对照者进行CCND 1基因G870 A基因型检测。结果：AA基因型个体患肾细胞癌的风险是GG基因型个体的1.70倍（经年龄和性别校正的OR为1.70，95%95%CI为1.03 ~ 2.82，p = 0.039）。此外，A等位基因在增加肾细胞癌风险方面具有基因剂量效应（校正OR 1.30，95%CI 1.01至1.67，p = 0.045）。对于肿瘤分期，没有发现基因型频率的显着差异（p = 0.646）。结论CCND 1变异体A等位基因可能是散发性肾细胞癌发病的一个隐性或基因剂量效应的遗传易感因素。需要更广泛和更大规模的研究来澄清CCND 1基因型是否更具体地参与RCC或RCC在年轻时的组织学子集的发病。
PURPOSE Cyclin D1 (CCND1) mRNA is alternatively spliced to produce 2 transcripts (transcript-a and transcript-b), which may be modulated by a G870A single nucleotide polymorphism at the conserved splice donor site of exon 4. Previous studies have suggested a significant association between the CCND1 genotype and the development of various cancers. We explored the possible association between this polymorphism and the onset or disease statue of sporadic renal cell carcinoma (RCC). MATERIALS AND METHODS The CCND1 G870A genotype was determined in 191 RCC cases and in 400 controls by polymerase chain reaction restriction length polymorphism analysis. RESULTS Subjects with the AA genotype were at 1.70-fold significant higher risk for RCC than those with the GG genotype (age and sex adjusted OR 1.70, 95% 95% CI 1.03 to 2.82, p = 0.039). In addition, the A allele had a gene dose effect in increasing the risk of RCC (adjusted OR 1.30, 95% CI 1.01 to 1.67, p = 0.045). For tumor stage no significant difference in genotype frequency was found (p = 0.646). CONCLUSIONS These data suggest that the CCND1 variant A allele may be a genetic susceptibility factor with a recessive or gene dose effect for the onset of sporadic RCC. More extensive and larger studies are required to clarify whether the CCND1 genotype is more specifically involved in the onset of a histological subset of RCC or RCC at a younger age.