Ma Hongxia, Xu Liang, Yuan Jing, Shao Minhua, Hu Zhibin, Wang Feng, Wang Yi, Yuan Wentao, Qian Ji, Wang Ying, Xun Pengcheng, Liu Hongliang, Chen Weihong, Yang Lin, Jin Guangfu, Huo Xiang, Chen Feng, Shugart Yin Yao, Jin Li, Wei Qingyi, Wu Tangchun, Shen Hongbing, Huang Wei, Lu Daru
Department of Epidemiology and Biostatistics, Cancer Research Center of Nanjing Medical University, Nanjing, China.
Pharmacogenet Genomics. 2007 Jun;17(6):417-23. doi: 10.1097/01.fpc.0000239975.77088.17.
Low nucleotide excision repair (NER) capacity has been associated with increased risk of lung cancer. Excision repair cross-complementing group 1 (ERCC1) is one of the NER core enzymes, and polymorphisms in ERCC1 may lead to altered repair function of the enzyme and therefore confer predisposition to cancer. The goal of this study was to test the hypothesis that common variants in ERCC1 were associated with lung cancer risk.
The genotyping analyses for 7 selected single nucleotide polymorphisms in ERCC1 using the TaqMan assay was conducted in a case-control study of 1010 patients with incident lung cancer and 1011 cancer-free controls in a Chinese population.
We found that the variant genotypes of the rs3212948 C allele were associated with significantly decreased risk of lung cancer [adjusted odds ratio (OR)=0.73 (95% CI=0.60-0.88) for CG; 0.96 (95% CI=0.65-1.41) for CC and 0.76 (95% CI=0.63-0.91) for CG/CC, compared with the GG genotype]. Similarly, a significant protective effect was also evident for the variant genotypes of rs1007616 C/T [adjusted OR=0.72 (95% CI=0.59-0.89) for CT; 0.90 (95% CI=0.61-1.35) for TT and 0.75 (95% CI=0.62-0.91) for CT/TT, compared with the CC genotype]. Stratified analysis revealed that the protective effects of these 2 single nucleotide polymorphisms were both more evident among young patients and patients without family history of cancer. Consistently, when assessing each unique haplotype compared with the most common haplotype 'TAGCACG', lung cancer risk was significantly decreased among patients who carried the haplotype 'TCCCATT' with the variant rs3212948C and rs1007616T alleles (P value=0.0340, P-sim=0.0325, adjusted OR=0.78; 95% CI=0.63-0.97).
These findings indicate that ERCC1 polymorphisms may contribute to the etiology of lung cancer. Further functional studies were warranted to elucidate the mechanism of the associations.
低核苷酸切除修复（NER）能力与肺癌风险增加相关。切除修复交叉互补基因1（ERCC1）是NER核心酶之一，ERCC1基因多态性可能导致该酶修复功能改变，从而使人易患癌症。本研究的目的是检验ERCC1常见变异与肺癌风险相关这一假设。
采用TaqMan分析法对1010例新发肺癌患者和1011例无癌对照的中国人群进行ERCC1基因7个单核苷酸多态性的基因分型分析。
我们发现，rs3212948 C等位基因的变异基因型与肺癌风险显著降低相关[与GG基因型相比，CG的校正比值比（OR）=0.73（95%可信区间[CI]=0.60 - 0.88）；CC的校正OR=0.96（95% CI=0.65 - 1.41）；CG/CC的校正OR=0.76（95% CI=0.63 - 0.91）]。同样，rs1007616 C/T的变异基因型也有显著的保护作用[与CC基因型相比，CT的校正OR=0.72（95% CI=0.59 - 0.89）；TT的校正OR=0.90（95% CI=0.61 - 1.35）；CT/TT的校正OR=0.75（95% CI=0.62 - 0.91）]。分层分析显示，这2个单核苷酸多态性的保护作用在年轻患者和无癌症家族史的患者中更为明显。一致的是，当将每种独特单倍型与最常见单倍型“TAGCACG”进行比较时，携带rs3212948C和rs1007616T等位基因变异的“TCCCATT”单倍型患者的肺癌风险显著降低（P值=0.0340，P模拟值=0.0325，校正OR=0.78；95% CI=0.63 - 0.97）。
这些发现表明ERCC1基因多态性可能参与肺癌的病因学。有必要进行进一步的功能研究以阐明其关联机制。
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