OBJECTIVETo assess the association between polymorphisms of insulin-like growth factor receptor (IGF-1R and IGF-2R) and genetic susceptibility and non-small-cell lung cancer (NSCLC).

METHODSA case-control study of 260 patients with NSCLC and 258 cancer-free subjects from Fujian was carried out. Genotypes of polymorphisms of IGF-1R +1013 and IGF-2R +1619 were determined by DNA sequencing and polymerase chain reaction-restrictive fragment length polymorphism.

RESULTS(1) Significant differences in allele frequency and genotypes distribution of IGF-1R +1013 (G/A) were found between the two groups (P<0.05). On multivariate analysis after controlling age and gender, compared with GG genotype of the IGF-1R +1013 (G/A), the risk of lung cancer for individuals with GA genotype was increased by 0.80 times (95%CI: 1.24-2.59, P = 0.002), those with AA genotype was increased by 2.56 times (95%CI: 1.78-7.26, P = 0.000), and those with the polymorphic A variant (GA or AA) was increased by 0.98 times (95%CI: 1.39-2.83, P = 0.000). No significant differences in genotypic or allelic frequencies of IGF-2R +1619 (G/A) were found between the two groups (P> 0.05). (2) After stratification of the clinical status, the IGF-1R +1013 A allele increased 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: 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 no association was found between the two SNPs and other clinical features. (3) IGF-1R +1013 (G/A) and IGF-2R +1619(G/A) polymorphisms showed a synergic effect (P = 0.003).

CONCLUSIONThe common IGF-1R gene polymorphism G1013A may influence the risk of lung cancer. The polymorphisms of IGF-1R +1013 (G/A) and IGF-2R +1619 (G/A) have synergistic influence on the risk of lung cancer.