Association of Tissue Inhibitor of Metalloproteinase-1 Genotypes with Lung Cancer Risk in Taiwan

AIM: Tissue inhibitors of metalloproteinases (TIMPs) are a family of multifunctional proteins whose expression has been shown to be up-regulated in various types of cancer. However, the contribution of TIMPs to lung cancer is not known. The present study aimed to evaluate the contribution of TIMP1 rs4898, rs6609533 and rs2070584 genetic polymorphisms to the risk of lung cancer.MATERIALS AND METHODS: The contributions of these TIMP1 genotypes to lung cancer risk were investigated in 358 patients with lung cancer patients and 716 age- and gender-matched healthy controls.RESULTS: The results showed that the percentages of TT, CT and CC for TIMP-1 rs4898 genotypes were 28.5%, 33.2% and 38.3% in the patient group and 34.5%, 41.2% and 24.3% in the non-cancer control group, respectively (p for trend=1.21×10(-5)). The CC genotype carriers were at higher risk for lung cancer (odds ratio=1.91, 95% confidence interval=1.38-2.63, p=0.0001) than the TT genotype carriers. We also analyzed the allelic frequency distributions and the results showed that the C allele of TIMP1 rs4898 increased lung cancer susceptibility (p=1.26×10(-5)). On the contrary, there was no difference in the distribution of genotypic or allelic frequencies among patients and the controls for TIMP1 rs6609533 and rs2070584.CONCLUSION: The CC genotype of TIMP1 rs4898 compared to the TT wild-type genotype may increase lung cancer risk in Taiwan and may serve as a marker for early detective and predictive purposes.