Yu Yunxian, Liu Hui, Jin Mingjuan, Zhang Mingwu, Pan Yifeng, Zhang Shanchun, Li Qilong, Chen Kun
Department of Epidemiology & Health Statistics, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China.
Ann Hum Genet. 2012 Jul;76(4):269-76. doi: 10.1111/j.1469-1809.2012.00709.x. Epub 2012 Apr 25.
Due to the high morbidity and mortality of colorectal cancer (CRC), this study aims to determine the joint association of RE-1-silencing transcription factor (REST) and nuclear factor-κB 1 (NFKB1) genes with CRC in a population-based study. A well-matched case-control study including 390 controls and 388 patients with CRC was enrolled in China. The selected single nucleotide polymorphisms (SNPs) in the REST and NFKB1 genes were genotyped by Illumina SnapShot Chip. After adjustment for important covariates, the associations of SNPs and joint association of REST and NFKB1 with CRC were evaluated by multiple logistic regression models. The subjects with the rs2228991 AA genotype of the REST gene had a decreased risk for CRC (OR = 0.38; 95%CI: 0.19-0.74), compared with the GG genotype. There were no significant associations between three SNPs in the NFKB1 gene, their haplotype and CRC risk. However, a significant combined effect of rs3774959 and rs3774964 in the NFKB1 gene with rs2228991 in the REST gene on CRC risk was observed. In conclusion, the present study found that mutation in the REST gene rather than the NFKB1 gene was associated with the risk of CRC. Furthermore, significant REST-NFKB1 joint association was observed for CRC, colon cancer and rectal cancer risk.
由于结直肠癌（CRC）的高发病率和高死亡率，本研究旨在通过一项基于人群的研究确定RE-1沉默转录因子（REST）和核因子κB 1（NFKB1）基因与CRC的联合关联。在中国开展了一项匹配良好的病例对照研究，纳入了390名对照和388例CRC患者。通过Illumina SnapShot芯片对REST和NFKB1基因中选定的单核苷酸多态性（SNP）进行基因分型。在对重要协变量进行调整后，通过多重逻辑回归模型评估SNP与REST和NFKB1与CRC的联合关联。与GG基因型相比，REST基因rs2228991 AA基因型的受试者患CRC的风险降低（OR = 0.38；95%CI：0.19 - 0.74）。NFKB1基因中的三个SNP、它们的单倍型与CRC风险之间无显著关联。然而，观察到NFKB1基因中的rs3774959和rs3774964与REST基因中的rs2228991对CRC风险有显著的联合效应。总之，本研究发现REST基因而非NFKB1基因的突变与CRC风险相关。此外，观察到REST - NFKB1联合关联对CRC、结肠癌和直肠癌风险有显著影响。
