Insulin-like Growth Factor Receptor Gene Polymorphism And Susceptibility As Well As Platinum-based Chemotherapy Outcomes To Non-small Lung Cancer

Objective Insulin-like growth factor1receptor (IGF-1R) gene is an importantregulator of many aspects of growth,differentiatiation,anddevelopment.Insulin-likegrowth factor2receptor（IGF-2R）gene is a negative mediator for carcinogenesis.Cancer.This study evaluate the contribution of IGF-1R+1013(G/A) and IGF-2R+1619(G/A) polymorphism to risk of the development and response to platinum-basedchemothempy of NSCLC．Methods260patients with lung cancer and258cancer-free subjects as a controlgroup was conducted to explore polymorphisms of IGF-1R+1013（G/A）、IGF-2R+1619（G/A）.Genotypes were evaluated by the polymerase chain reaction-restrictive fragment length polymorphism(PCR-RFLP) method,and odds ratios and95％confidence intervals were estimated by multivariate logistic regression. Accordin-g to the genotypes，a comparison of chemotherapy outcome in132NSCLC patientswas executed. single variant Kaplan-Meier log-rank test were used to analyze theassociation between these genetic polymorphisms and MST. Cox model assess theimpact factor of the efficacy of chemotherapy.Results1）Significant differences in genotypes of IGF-1R+1013(G/A) were foundbetween lung cancer cases and controls，P<0.05. On multivariate analysis controllingfor age and gender,compared with that of the IGF-1R+1013（G/A）GG genotypecarriers, the risk of lung cancer for the individuals with GA genotype was increasedby0.80times(95%CI：1.24-2.59，P=0.002), the individuals with AA genotype wasincreased by2.56times (95%CI：1.78-7.26，P=0.000), the individuals with thepolymorphic A variant (GA+AA)was increased by0.98times (95%CI：1.39-2.83， P=0.000). No significant differences for the genotype frequencies or the allelefrequencies of the IGF-2R+1619（G/A） were found between lung cancer cases andcontrols (P>0.05).The two SNPs showed a synergic effect on the risk of lung cancer.2)After stratification analysis according to clinical status, the IGF-1R+1013A alleleincrease the risk of lung squamous cell carcinoma（OR=3.20，95%CI:1.75-5.84，P=0.000）、lung adenocarcinoma（OR=1.55，95%CI:95%CI:1.00-2.41，P=0.049）and other types of lung cancer（OR=1.96，95%CI:1.10-3.49，P=0.023）, but norelationship was found between two SNPs and other clinical features.3)No significantassociation was found between IGF-1R+1013(G/A) and IGF-2R+1619(G/A)polymorphisms with clinical benefit, P>0.05. Furthermore,we found that the twoSNPs couldn’t work together,P>0.05. MST of patients with IGF-1R+1013(G/A)genotypes with A allele (GA+AA)were significantly shorter than those of GGgenotype carriers(χ2=5.721，P=0.017). There was no difference of MST in patientswith IGF-2R+1619(G/A) A allele carrier(GA+AA)and GG genotype carrier(χ2=0.341，P=0.575). The two SNPs showed a synergic effect on MST(P <0.05),Estimation by Cox proportional hazards model showed that IGF-1R+1013(G/A)polymorphism is an independent prognostic factors, P=0.020,and IGF-1R+1013(G/A)polymorphism in combination with IGF-2R+1619(G/A) polymorphism is aslo theindependent prognostic factors in advanced NSCLC, P=0.025.Conclusion1)the common IGF-1R gene polymorphism G1013A modulates the riskof lun cancer.The polymorphisms of IGF-1R+1013（G/A）、IGF-2R+1619（G/A）havesynergistic effect on the risk of lung cancer.2)IGF-1R+1013(G/A) polymorphismalone or in combination with IGF-2R+1619(G/A) polymorphism had associationwith MST in patients with advanced NSCLC after treatment with platin-basedchemotherapy which might be aprognostic factor in platin-treated patients with advan-ced NSCLC.