| The incidence of lung cancer has been increasing over recent decades. Previous studies show that polymorphisms of the genes involved in carcinogen-detoxication, DNA repair and cell cycle control compose of the risk factors for lung cancer. Recent observations reveal that the components of CAK: Cdk7, MAT1 and cyclin H, may play important roles in cell cycle control, transcriptional control, and DNA repairing process, all of which are important in carcinogenesis. To test whether the genetic variants of CAK genes modify the risk of lung cancer, we compared the manifestation of 25 single nucleotide polymorphisms (SNPs) and the haplotypes of Cdk7, MAT1 and cyclin H between 500 patients with lung cancer and 517 heathy controls. Our results indicated that the genotype frequency of rs2020892 (p=0．042) and rs973063 (p=0．005) of cases significantly differed from those of the controls. Further analyses revealed that rs3093816, rs2284704, rs4151208, rs2020892 and rs973063 significantly influenced the susceptibility of lung cancer in a dominant genetic model while rs3093819 and rs4151183 did in a recessive model. Strongest association between cyclin H alleles and lung cancer patients was found in the non-smoke subpopulation. The haplotype 'TAC' (p=0．007) increased and the haplotype 'TTC' (p=0．043) decreased the risk of lung cancer. The potential gene-gene and gene-environmental interactions on lung cancer risk was evaluated using MDR software. A significant interaction between the three CAK component genes was identified and the combination of smoking status and genetic factors barely increased the accuracy. Our results suggested that genetic variants in CAK genes, Cdk7, cyclin H, MAT1, might modulate the risk of lung cancer in a gene-gene interaction mode, which consist to the biochemical interaction of corresponding proteins.In the second part of our study, we tested the association between ERCC1 polymorphisms and cancer by Meta-analysis. ERCC1 is a subunit of the NER 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, Pheterogeneity =0．001) on a worldwide population. Meta-analysis under other genetic contrasts did not reveal any significant association of T19007C to cancer in a worldwide population, 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% Cl 0．69-1．29, Pheterogeneity =0．0001) on a worldwide population. No significant effect of 8092A allele (3,865 patients and 3,750 controls) on cancer risk worldwidely (P=0．85, OR=1．01 95%CI 0．94-1．08, Pheterogeneity =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 arised 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. |
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