Li Yuanchun, Gu Shaohua, Wu Qihan, Li Yao, Fu Xuping, Mao Yumin, Huang Yan, Xie Yi
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, People's Republic of China.
Eur J Hum Genet. 2007 Sep;15(9):967-73. doi: 10.1038/sj.ejhg.5201855. Epub 2007 May 23.
ERCC1 (excision repair cross complementation group 1) is a subunit of the nucleotide excision repair complex, which can perform DNA strand incision correction of DNA damage. Association studies on the ERCC1 polymorphisms (C8092A and T19007C) in cancer had shown conflicting results. We performed a meta-analysis from all eligible case-control studies to assess the purported associations. Overall, the 19007C allele (3 853 patients and 4 349 controls) showed no significant effect on cancer risk compared to 19007T allele (P=0.39, odds ratio (OR)=0.95; 95% confidence interval (CI) 0.85-1.06, P(heterogeneity)=0.001) in all subjects. Meta-analysis under other genetic contrasts did not reveal any significant association of T19007C to cancer in all subjects, Caucasians and Asians. The 19007C allele (2 279 patients and 2 808 controls) showed no significant effect on lung cancer risk compared to 19007T allele (P=0.72, OR=0.94, 95% CI 0.69-1.29, P(heterogeneity)=0.0001) in all subjects. No significant effect of 8092A allele (3 865 patients and 3 750 controls) on cancer risk in all subjects (P=0.85, OR=1.01, 95% CI 0.94-1.08, P(heterogeneity)=0.92) and in Caucasians and Asians compare to 8092C. No evidences of association of C8092A (501 patients and 620 controls) to squamous cell carcinoma were found. The accumulated evidence indicated ERCC1 T19007C and C8092A might not be risk factors for cancer. Significant between-study heterogeneity existed in T19007C, which arose from a study showing significant protecting effect of 19007C allele compare to 19007T allele in smokers. More studies based on larger, stratified case-control population should be required to further evaluate the role of ERCC1 C8092A and T19007C polymorphisms in different cancer, especially in smokers.
ERCC1(切除修复交叉互补组1)是核苷酸切除修复复合物的一个亚基,可对DNA损伤进行DNA链切口校正。关于癌症中ERCC1基因多态性(C8092A和T19007C)的关联研究结果相互矛盾。我们对所有符合条件的病例对照研究进行了荟萃分析,以评估所声称的关联。总体而言,在所有受试者中,与19007T等位基因相比,19007C等位基因(3853例患者和4349例对照)对癌症风险无显著影响(P = 0.39,比值比(OR)= 0.95;95%置信区间(CI)0.85 - 1.06,P(异质性)= 0.001)。在其他基因对比下的荟萃分析未发现T19007C与所有受试者、白种人和亚洲人患癌症之间存在任何显著关联。在所有受试者中,与19007T等位基因相比,19007C等位基因(2279例患者和2808例对照)对肺癌风险无显著影响(P = 0.72,OR = 0.94,95% CI 0.69 - 1.29,P(异质性)= 0.0001)。与8092C相比,8092A等位基因(3865例患者和3750例对照)对所有受试者、白种人和亚洲人的癌症风险均无显著影响(P = 0.85,OR = 1.01,95% CI 0.94 - 1.08,P(异质性)= 0.92)。未发现C8092A(501例患者和620例对照)与鳞状细胞癌之间存在关联的证据。累积证据表明ERCC1 T19007C和C8092A可能不是癌症的危险因素。T19007C存在显著的研究间异质性,这源于一项研究表明,与19007T等位基因相比,19007C等位基因在吸烟者中有显著的保护作用。需要更多基于更大规模、分层病例对照人群的研究来进一步评估ERCC1 C8092A和T19007C基因多态性在不同癌症中的作用,尤其是在吸烟者中。