Effects of cyclin D1 polymorphism on age of onset of hereditary nonpolyposis colorectal cancer.
Effects of cyclin D1 polymorphism on age of onset of hereditary nonpolyposis colorectal cancer.
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发表时间：
2000-01
期刊：
影响因子：
11.2
通讯作者：
Shouming Kong;Christopher I. Amos;Rajyalakshmi Luthra;Patrick M. Lynch;B. Levin;Marsha L. Frazier
中科院分区：
文献类型：
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作者：
Shouming Kong;Christopher I. Amos;Rajyalakshmi Luthra;Patrick M. Lynch;B. Levin;Marsha L. Frazier
细胞周期蛋白 D1 基因中常见的多态性增强了该基因的交替剪接。选择性剪接产物编码一种改变的蛋白质，该蛋白质不包含参与蛋白质周转的序列。我们发现，突变等位基因纯合或杂合的遗传性非息肉病结直肠癌患者比正常等位基因纯合的患者平均早 11 年患结直肠癌。这是第一份表明细胞周期蛋白 D1 多态性影响癌症发病年龄的报告。由于细胞周期蛋白 D1 在细胞周期的 G1 到 S 期转变中发挥重要作用，我们的研究结果表明，具有突变等位基因的细胞由于错配修复缺陷而积累突变，并且也可能比不携带多态性的细胞更容易绕过细胞周期的 G1-S 检查点。该多态性具有显性表型。
A common polymorphism in the cyclin D1 gene enhances the gene's alternate splicing. The alternatively spliced product encodes an altered protein that does not contain sequences involved in the turnover of the protein. We found that hereditary nonpolyposis colorectal carcinoma patients who were homozygous or heterozygous for the mutant allele developed colorectal cancer an average of 11 years earlier than patients who were homozygous for the normal alleles. This is the first report indicating that the cyclin D1 polymorphism influences age of onset of cancer. Because cyclin D1 plays an important role in the G1 to S phase transition of the cell cycle, our findings suggest that cells with the mutant allele accumulate mutations as a result of defective mismatch repair and may also bypass the G1-S checkpoint of the cell cycle more easily than in cells not carrying the polymorphism. The polymorphism has a dominant phenotype.