title: [Relationship of insulin-like growth factor receptor single nucleotide polymorphism (SNP) with platinum-based chemotherapy outcomes in advanced non-small cell lung cancer].
abstract: OBJECTIVE
  It has been proven that the insulin-like growth factor 1 receptor (IGF-1R) gene is an important regulator of many aspects of growth, differentiation, and development. The insulin-like growth factor 2 receptor (IGF-2R) gene is a negative mediator for carcinogenesis. The aim of this study is to investigate the relationship of IGF-1R+1013(G/A) and IGF-2R+1619(G/A) single nucleotide polymorphism (SNP) with platinum-based chemotherapy outcomes in advanced non-small cell lung cancer (NSCLC).
  
  
  METHODS
  A total of 132 patients with NSCLC were routinely treated with platinum-based chemotherapy, and their clinical responses were evaluated after four cycles of chemotherapy. IGF-1R+1013(G/A) and IGF-2R+1619(G/A) were genotyped using polymerase chain reaction-restrictive fragment length polymorphism. The relationship between IGF-1R+1013(G/A) and IGF-2R+1619(G/A) genotypes and the clinical benefit rate, as well as the median survival time (MST), was analyzed.
  
  
  RESULTS
  No significant association was found between IGF-1R+1013(G/A) and IGF-2R+1619(G/A) polymorphisms with clinical benefit (P>0.05). Further, we found that the two SNPs could not work together (P=0.975). The MST of patients with IGF-1R+1013(G/A) genotypes with A allele (GA+AA) was significantly shorter than that of GG genotype carriers (P=0.017). There was no significant difference in MST in patients with IGF-2R+1619(G/A) A allele (GA+AA) carrier and GG genotype carrier (P=0.575). The two SNPs showed a synergistic effect on MST. Patients who carried a mutant allele A of IGF-1R+1013(G/A) and a mutant allele A of IGF-2R+1619(G/A) had a MST of 12 months, which was significantly shorter than that of patients with other genotypes (P<0.05). Estimation by the Cox proportional hazards model showed that IGF-1R+1013(G/A) polymorphism is an independent prognostic factor (P=0.020), and IGF-1R+1013(G/A) polymorphism in combination with IGF-2R +1619(G/A) polymorphism is an independent prognostic factor in advanced NSCLC (P=0.025).
  
  
  CONCLUSIONS
  IGF-1R+1013(G/A) polymorphism alone or in combination with IGF-2R +1619(G/A) polymorphism was associated with the overall survival period in patients with advanced NSCLC after treatment with platin-based chemotherapy, which might be a prognostic factor in platin-treated patients with advanced NSCLC.
authors.affiliation: Fujian Provincial Medical College, Fujian Medical University, Fuzhou 350001, China. slyyywb@yahoo.com.cn
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Shao
authors.forename: Hongru
authors.initials: H
authors.lastname: Li
authors.forename: Lili
authors.initials: L
authors.lastname: Han
authors.forename: Xiang'e
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010984:Platinum / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017526:Receptor, IGF Type 1 / Q000235:genetics; D017527:Receptor, IGF Type 2 / Q000235:genetics; D017451:Receptors, Somatomedin / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D017527:Receptor, IGF Type 2; D017451:Receptors, Somatomedin; D010984:Platinum; D017526:Receptor, IGF Type 1