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染色体易位断点和免疫功能基因的遗传变异与非霍奇金淋巴瘤的风险。

Genetic variation in chromosomal translocation breakpoint and immune function genes and risk of non-Hodgkin lymphoma.

机构信息

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

出版信息

Cancer Causes Control. 2010 May;21(5):759-69. doi: 10.1007/s10552-010-9504-y. Epub 2010 Jan 20.

Abstract

BACKGROUND

Tumor necrosis factor (TNF) and interleukin 10 (IL10) are promising candidate susceptibility genes for non-Hodgkin lymphoma (NHL). Chromosomal translocation breakpoint genes are of interest, given their documented involvement in lymphoma progression.

METHODS

We analyzed 11 polymorphisms in BCL2, CCND1, MYC, TNF, and IL10 in a large, population-based, Danish-Swedish case-control study including 2,449 NHL cases and 1,980 controls. Relative risk of NHL was computed as odds ratios (OR).

RESULTS

There was no clear evidence of associations between variants in BCL2, CCND1, and MYC and risk of NHL overall or subtypes. TNF rs1800629 was associated with risk of NHL (OR 1.53, 95% confidence interval, CI, 1.06-2.19 for minor allele homozygosity), T-cell lymphoma (OR 2.54, CI 1.27-5.09) and mantle cell lymphoma (OR 2.84, CI 1.38-5.87). IL10 rs1800890 was associated with risk of diffuse large B-cell lymphoma (OR 1.41, CI 1.08-1.85 for minor allele homozygosity) and mantle cell lymphoma (OR 1.77, CI 1.04-3.00). We did not replicate a previously reported interaction with autoimmunity.

CONCLUSIONS

We found no support for a role of the studied variants in BCL2, CCND1, or MYC in risk of NHL or subtypes, but we provide further evidence of putative susceptibility loci in TNF and IL10 for specific NHL subtypes.

摘要

背景

肿瘤坏死因子(TNF)和白细胞介素 10(IL10)是非霍奇金淋巴瘤(NHL)有前途的候选易感基因。鉴于染色体易位断点基因在淋巴瘤进展中的作用已得到证实,因此这些基因具有研究意义。

方法

我们在一项大型基于人群的丹麦-瑞典病例对照研究中分析了 BCL2、CCND1、MYC、TNF 和 IL10 中的 11 个多态性,该研究纳入了 2449 例 NHL 病例和 1980 例对照。通过计算比值比(OR)来计算 NHL 的相对风险。

结果

BCL2、CCND1 和 MYC 中的变体与 NHL 整体或亚型的风险之间没有明显的关联证据。TNF rs1800629 与 NHL 风险相关(OR 1.53,95%置信区间,CI,1.06-2.19 为次要等位基因纯合性)、T 细胞淋巴瘤(OR 2.54,CI 1.27-5.09)和套细胞淋巴瘤(OR 2.84,CI 1.38-5.87)。IL10 rs1800890 与弥漫性大 B 细胞淋巴瘤(OR 1.41,95%置信区间,CI,1.08-1.85 为次要等位基因纯合性)和套细胞淋巴瘤(OR 1.77,CI 1.04-3.00)的风险相关。我们没有复制先前报道的与自身免疫的相互作用。

结论

我们没有发现研究的变体在 NHL 或亚型的风险中起作用的证据,但我们为 TNF 和 IL10 中特定 NHL 亚型的潜在易感基因提供了进一步的证据。

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