Association of single-nucleotide polymorphisms in the cell cycle genes with breast cancer in the British population.
Association of single-nucleotide polymorphisms in the cell cycle genes with breast cancer in the British population.
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DOI：
10.1093/carcin/bgm284
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发表时间：
2008-02
期刊：
影响因子：
4.7
通讯作者：
Studies in Epidemiology and Risks of Cancer Heredity (SEARCH) Team
中科院分区：
文献类型：
--
作者：
Driver KE;Song H;Lesueur F;Ahmed S;Barbosa-Morais NL;Tyrer JP;Ponder BA;Easton DF;Pharoah PD;Dunning AM;Studies in Epidemiology and Risks of Cancer Heredity (SEARCH) Team
通过一项大规模的病例对照研究，我们检查了细胞周期途径中13个基因中常见的单核苷酸多态(SNPs)是否与乳腺癌风险有关。利用79个标签SNPs对CCND1、CCND2、CCND3、CCNE1、CDK2、CDK4、CDK6、CDKN1A、CDKNIB、CDKN2A/CDKN2B、CDKN2C和CDKN2D等240个常见SNPs进行了分析。在流行病学和癌症遗传风险研究(SEARCH)研究中，对2270名患者和2280名对照进行了这些基因分型。来自同一人群的2200名患者和2280名对照的TAG SNPs基因分型显示，病例和对照组之间存在统计学上的显著差异(P<；0.1)。该方法在4个细胞周期基因中发现了与乳腺癌相关的SNPs：细胞周期蛋白CCNE1rs997669的优势比(OR)(GG/AA)为1.18[95%可信区间(95%CI)1.04~1.34]，P=0.003；CDKN1B rs34330：OR(TT/CC)=1.22(95%CI1.02-1.47)，P=0.013；CDKN2a/2B rs3731239：OR(CC/TT)=0.9(95%CI0.79-1.03)，P=0.013；在我们的研究人群中，我们能够排除D型细胞周期蛋白、细胞周期蛋白依赖性激酶、CDKN2C和CDKN2D与乳腺癌有任何显著的关联。这里考虑的细胞周期基因的综合效应在一项全球测试中提供了与乳腺癌风险显著相关的证据(P-异质性=0.010，P-趋势=0.048)。还需要进一步的大规模研究来证实这些结果。
Using a large-scale case–control study, we examined whether common single-nucleotide polymorphisms (SNPs) within 13 genes involved in the cell cycle pathway are associated with breast cancer risk. Seventy-nine tag SNPs were used to evaluate 240 common SNPs found in the genes: CCND1, CCND2, CCND3, CCNE1, CDK2, CDK4, CDK6, CDKN1A, CDKNIB, CDKN2A/CDKN2B, CDKN2C and CDKN2D. These were genotyped in 2270 cases and 2280 controls from the Studies in Epidemiology and Risks of Cancer Heredity (SEARCH) study. Tag SNPs showing evidence of statistically significant differences between cases and controls (P < 0.1) were genotyped in a further 2200 cases and 2280 controls from the same population. This approach found evidence for breast cancer-associated SNPs in four of the cell cycle genes: the cyclin CCNE1 rs997669 had an odds ratio (OR) (GG/AA) of 1.18 [95% confidence interval (95% CI) 1.04–1.34] P = 0.003 and the cyclin-dependent kinase inhibitors—CDKN1A rs3176336: OR (TT/AA) = 1.25 (95% CI 1.11–1.42) P = 0.0026; CDKN1B rs34330: OR (TT/CC) = 1.22 (95% CI 1.02–1.47) P = 0.013 and the region of CDKN2A/2B rs3731239: OR (CC/TT) = 0.90 (95% CI 0.79–1.03) P = 0.013 and rs3218005 OR (GG/AA) = 1.55 (95% CI 1.02–2.37) P = 0.013 (P-values unadjusted for multiple testing). We were able to exclude the D-type cyclins, cyclin-dependent kinases, CDKN2C and CDKN2D from having any significantly associated risk with breast cancer in our study population. The combined effects of the cell cycle genes considered here provide evidence for a significant association with breast cancer risk in a global test (P-heterogeneity = 0.010, P-trend = 0.048). Further large-scale studies are needed to confirm these results.
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作者：
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