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慢性淋巴细胞白血病的遗传易感性变异。

Genetic susceptibility variants for chronic lymphocytic leukemia.

机构信息

Mayo Clinic College of Medicine, 200 1st Street Southwest, Rochester, MN 55905, USA.

出版信息

Cancer Epidemiol Biomarkers Prev. 2010 Apr;19(4):1098-102. doi: 10.1158/1055-9965.EPI-09-1217. Epub 2010 Mar 23.

Abstract

BACKGROUND

There is strong and consistent evidence that a genetic component contributes to the etiology of chronic lymphocytic leukemia (CLL). A recent genome-wide association study of CLL identified seven genetic variants that increased the risk of CLL within a European population.

METHODS

We evaluated the association of these variants, or variants in linkage disequilibrium with these variants, with CLL risk in an independent sample of 438 CLL cases and 328 controls.

RESULTS

Of these seven single nucleotide polymorphisms (SNP), six had P trend < 0.05 and had estimated odds ratios (OR) that were strikingly comparable to those of the previous study. Associations were seen for rs9378805 [OR, 1.47; 95% confidence intervals (CI), 1.19-1.80; P trend = 0.0003] near IRF4 and rs735665 near GRAMD1B (OR, 1.47; 95% CI, 1.14-1.89; P trend = 0.003). However, no associations (P > 0.05) were found for rs11083846, nor were any found for any SNP in linkage disequilibrium with rs11083846.

CONCLUSIONS

Our results confirm the previous findings and further support the role of a genetic basis in the etiology of CLL; however, more research is needed to elucidate the causal SNP(s) and the potential manner in which these SNPs or linked SNPs function in CLL pathogenesis.

摘要

背景

有强有力且一致的证据表明,遗传因素是慢性淋巴细胞白血病(CLL)发病机制的一个重要因素。最近对 CLL 的全基因组关联研究确定了七个遗传变异,这些变异增加了欧洲人群 CLL 的发病风险。

方法

我们评估了这些变体,或与这些变体连锁不平衡的变体,与 438 例 CLL 病例和 328 例对照的 CLL 风险之间的关联。

结果

在这七个单核苷酸多态性(SNP)中,有六个 SNP 的 P 趋势<0.05,且其估计的比值比(OR)与之前的研究非常相似。rs9378805 附近的 IRF4 和 rs735665 附近的 GRAMD1B 存在关联(OR,1.47;95%置信区间[CI],1.19-1.80;P 趋势=0.0003)。然而,rs11083846 没有关联(P>0.05),也没有发现与 rs11083846 连锁不平衡的任何 SNP 存在关联。

结论

我们的结果证实了之前的发现,并进一步支持遗传基础在 CLL 发病机制中的作用;然而,需要更多的研究来阐明因果 SNP 以及这些 SNP 或连锁 SNP 在 CLL 发病机制中的潜在作用方式。

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