Cyclin D1 gene polymorphism as a risk factor for oral premalignant lesions
Cyclin D1 gene polymorphism as a risk factor for oral premalignant lesions
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DOI：
10.1093/carcin/bgl048
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发表时间：
2006-10-01
期刊：
影响因子：
4.7
通讯作者：
Wu, Xifeng
中科院分区：
文献类型：
--
作者：
Huang, Maosheng;Spitz, Margaret R.;Wu, Xifeng
背景：细胞周期失调在肿瘤发生中起着重要作用。细胞周期蛋白 D1 基因 (CCND1) 是细胞周期 G(1) 期的关键调节因子。方法：在这项针对 115 名口腔癌前病变 (OPL) 患者和 230 名对照患者的病例对照研究中，我们对外显子 4 剪接位点 (G870A) 的 CCND1 单核苷酸多态性 (SNP) 进行了基因分型，并确定了该 SNP 与发生 OPL 风险的关联。结果：我们发现杂合变异等位基因 (GA)、纯合变异等位基因 (AA) 和 OPL 风险之间存在显着相关性，调整后的比值比 (OR) 分别为 1.91 [95% 置信区间 (CI)，1.05-3.48] 和 2.38 (95% CI，1.16-4.87)。至少具有一种变异等位基因的个体的 OR 为 2.04 (95% CI, 1.15-3.60)。当进行进一步的分层分析时，年轻个体（OR = 2.82；95% CI，1.32-6.02）、男性（OR = 2.97；95% CI，1.31-6.71）和从不吸烟者（OR = 2.92；95% CI，1.09-7.82）中风险增加更为明显。最后，我们发现变异等位基因与吸烟状况之间存在联合效应。以野生型（GG）基因型从不吸烟者为参照组，变异基因型（G/A+A/A）从不吸烟者、G/G基因型吸烟者和G/A+A/A基因型吸烟者的OR分别为2.92（1.09-7.82）、3.95（1.36-11.5）和7.01。分别为（2.68-18.4）。结论：我们的结果表明 CCND1 G870A SNP 可能导致 OPL 的遗传易感性并参与口腔癌的发展。
Background: Deregulation of cell cycle plays an important role in tumorigenesis. Cyclin D1 gene (CCND1) is a key regulator of the G(1) phase of the cell cycle. Methods: In this case-control study of 115 oral premalignant lesion (OPL) patients and 230 controls, we genotyped the CCND1 single nucleotide polymorphism (SNP) at the exon 4 splice site (G870A) and determined the association of this SNP with the risk of developing OPLs. Results: We found significant associations between the heterozygous variant allele (GA), the homozygous variant allele (AA) and OPL risk, with adjusted odds ratios (ORs) of 1.91 [95% confidenc interval (CI), 1.05-3.48] and 2.38 (95% CI, 1.16-4.87), respectively. The OR for individuals with at least one variant allele was 2.04 (95% CI, 1.15-3.60). When further stratified analyses were performed, the increased risk was more evident in younger individuals (OR = 2.82; 95% CI, 1.32-6.02), in men (OR = 2.97; 95%CI, 1.31-6.71) and in never smokers (OR = 2.92; 95% CI, 1.09-7.82). Finally, we found joint effects between the variant alleles and the smoking status. Using never smokers with the wild-type (GG) genotypes as the reference group, the ORs for never smokers with the variant genotypes (G/A + A/A), smokers with the G/G genotype and smokers with the G/A + A/A genotypes were 2.92 (1.09-7.82), 3.95 (1.36-11.5) and 7.01 (2.68-18.4), respectively. Conclusion: Our results suggest that the CCND1 G870A SNP may contribute to genetic susceptibility to OPLs and involve in oral cancer development.