Abstract
Objective To investigate the relationship between 418 C>G polymorphism of tissue metalloproteinase inhibitor-2(TIMP-2)gene and susceptibility to non-small cell lung cancer(NSCLC).Methods A total of 167 patients with NSCLC admitted to Suining Central Hospital from May 2021 to May 2023 were selected as the observation group,and 183 healthy subjects who underwent physical examination in the hospital during the same period were selected as the control group.The general data of the two groups were compared and the polymorphism of the TIMP-2 gene was analyzed.The genotype and allele frequency distribution of the polymorphic locus of the TIMP-2 gene were detected and compared between the two groups.Logistic regression was used to analyze the correlation between TIMP-2 gene 418 C>G site and NSCLC.Results The proportion of BMI≥24kg/m2 and smoking in the observation group were 67.07%and 61.08%,respectively,which were 44.26%and 40.44%in the control group,and the differences were statistically significant(χ2=18.356,14.881,all P<0.001).The variant GG homozygote produced three fragments of 230bp,51bp and 23bp in length,the wild-type CC homozygote produced 253bp and 51bp in length,and the heterozygous GC produced four pieces of 253bp,230bp,51bp and 23bp in length.The 51bp and 23bp fragments were not shown,and the TIMP-2 418 C>G gene identity was 100%.The genotype frequencies met the Hardy-Weinberg genetic equilibrium(P>0.05).The frequencies of CC,GC and GG of the TIMP-2 genotype in the observation group were 10.18%,41.92%and 47.90%,respectively,and those in the control group were 4.37%,37.70%and 57.92%,respectively,and the difference was statistically significant(χ2=6.163,P=0.046).The frequencies of the C and G alleles of TIMP-2 in the observation group were 31.14%and 68.86%,respectively,and those in the control group were 23.22%and 76.78%,respectively,and the difference was statistically significant(χ2=5.549,P=0.018).Compared with the control group Logistic regression analysis showed that genotype carrying the C allele significantly increased the risk of NSCLC(OR=2.669,95%CI:1.478~2.936,P<0.01).Compared with the GG+GC group,the proportion of patients with CC genotype who had poor chromosome karyotype prognosis,the proportion of high-risk group in the International Prognostic Scoring System(IPSS)risk group and the levels of CRP and PCT were increased,and the differences were statistically significant(t=3.633~11.249,all P<0.001).Absolute neutrophil count(ANC),Haemoglobin(HGB)and Platelet(PLT)decreased,and the differences were statistically significant(t=4.760,2.015,2.212,all P<0.05).Multivariate COX regression analysis showed that CC genotype,chromosome karyotype,IPSS risk group,ANC,HGB,PLT,CRP,and PCT were risk factors for poor prognosis in NSCLC(Wald χ2=3.072~17.611,all P<0.05).The results of the multifactor dimensionality reduction(MDR)method showed that the interaction combination of abnormal ANC,HGB,PLT,CRP,and PCT levels and TIMP-2 gene polymorphism was 2.650 times higher than that of NSCLC.Conclusion The CC genotype and C allele of the 418 C>G locus of TIMP-2 gene are significantly associated with the risk of NSCLC and are independent risk factors for NSCLC.关键词
组织金属蛋白酶抑制剂-2基因/基因多态性/非小细胞肺癌/易感性Key words
tissue metalloproteinase inhibitor-2 gene/gene polymorphism/non-small cell lung cancer/susceptibility分类
临床医学