Cancer：NF-kB多态性与肺癌发病风险降低相关

    近日，刊登在国际著名癌症杂志Cancer上的一项研究报告指出，一种涉及炎症和免疫效应的基因突变和肺癌发病风险降低直接相关。

    这项研究由国立癌症研究中心的研究者进行，研究中，研究者对378位肺癌病人和450位健康个体中涉及炎症和免疫效应的1429个突变进行了分析，结果显示，肺癌和位于44个基因处的81个单核苷酸多态性（SNPs）直接相关。

    随后，研究者对比分析了结果，同时分析了对5739位肺癌患者以及5848个健康个体的全基因组向关联分析的结果，发现在81个SNPs中，名为rs4648127，位于基因NFKB1处的SNP和肺癌都具有明显的相关性，而且该SNP和肺癌风险降低相关，可以使得肺癌风险降低约44%。

    NF-kB或者细胞核因子kB，是NFKB1基因产生的一种重要的蛋白质，其通过调节基因表达、细胞死亡、增殖，在机体免疫系统和炎症反应上扮演着重要角色。此前研究表明，免疫反应和炎症或许会影响肺癌的发生，在这项研究中，研究者的研究结果揭示了炎症和肺癌发生之间存在相关性。后期研究者们还将继续研究NFKB1以及其和肺癌发生的关系。

与肺癌相关的拓展阅读：

• Cancer：NF-kB多态性与肺癌发病风险降低相关
• 男子吸烟，一家三口皆患肺癌
• 肺癌、食管癌治疗相关临床路径颁布
• Nature Genetics：大批量小细胞肺癌外显子组测序完成
• PNAS：血检可发现早期肺癌
更多信息请点击：有关肺癌更多资讯

编译自：Gene Variant Linked With Reduced Lung Cancer Risk

doi:10.1002/cncr.27605
PMC:
PMID:

Genetic variation in innate immunity and inflammation pathways associated with lung cancer risk

Meredith S. Shiels PhD, MHS1,¶,*, Eric A. Engels MD, MPH1, Jianxin Shi PhD2, Maria Teresa Landi MD, PhD3, Demetrius Albanes MD4, Nilanjan Chatterjee PhD2, Stephen J. Chanock MD5, Neil E. Caporaso MD3, Anil K. Chaturvedi PhD1

BACKGROUND: Pulmonary inflammation may contribute to lung cancer etiology. The authors conducted a broad evaluation of the association of single nucleotide polymorphisms (SNPs) in innate immunity and inflammation pathways with lung cancer risk and conducted comparisons with a lung cancer genome-wide association study (GWAS).

METHODS: In total, 378 patients with lung cancer (cases) and a group of 450 controls from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial were included. A proprietary oligonucleotide pool assay was used to genotype 1429 SNPs. Odds ratios and 95% confidence intervals were estimated for each SNP, and P values for trend (Ptrend) were calculated. For statistically significant SNPs (Ptrend < .05), the results were replicated with genotyped or imputed SNPs in the GWAS, and P values were adjusted for multiple testing.

RESULTS: In the PLCO analysis, a significant association was observed between lung cancer and 81 SNPs located in 44 genes (Ptrend < .05). Of these 81 SNPS, there was evidence for confirmation in the GWAS for 10 SNPs. However, after adjusting for multiple comparisons, the only SNP that retained a significant association with lung cancer in the replication phase was reference SNP rs4648127 (nuclear factor of kappa light polypeptide gene enhancer of B-cells 1 [NFKB1]) (multiple testing-adjusted Ptrend = .02). The cytosine-thymine (CT)/TT genotype of NFKB1 was associated with reduced odds of lung cancer in the PLCO study (odds ratio, 0.56; 95% confidence interval, 0.37-0.86) and the in the GWAS (odds ratio, 0.79; 95% confidence interval, 0.69-0.90).

CONCLUSIONS: A significant association was observed between a variant in the NFKB1 gene and the risk of lung cancer. The current findings add to evidence implicating inflammation and immunity in lung cancer etiology. Cancer 2012. Published 2012 by the American Cancer Society.

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