Faculty Collaboration Database

A 3'-untranslated region polymorphism in IGF1 predicts survival of non-small cell lung cancer in a Chinese population. Clin Cancer Res 2010 Feb 15;16(4):1236-44

Date

02/11/2010

Pubmed ID

20145156

DOI

10.1158/1078-0432.CCR-09-2719

Scopus ID

2-s2.0-76749087106 (requires institutional sign-in at Scopus site)   39 Citations

Abstract

PURPOSE: Disruption of the balance of insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP3) has been implicated in the etiology and progression of lung and other cancers. Single nucleotide polymorphisms (SNP) in IGF1 and IGFBP3 have been reported to be associated with the expression of the IGF-I/IGFBP3 axis. Therefore, we hypothesized that SNPs in these two genes were associated with lung cancer survival.

EXPERIMENTAL DESIGN: We selected and genotyped 21 tagging and potentially functional SNPs in IGF1 and IGFBP3 by using Illumina Goldengate Genotyping Chip in a case cohort of 568 patients diagnosed with non-small cell lung cancer (NSCLC) in a Chinese population. Log-rank test and Cox proportional hazard models were used for the survival analyses.

RESULTS: We found that rs5742714C/G in the 3'-untranslated region of IGF1 was associated significantly with NSCLC survival after adjustment for demographic and clinicopathologic factors, showing an improved median survival time in patients carrying variant CG/GG genotypes [median survival time, 28.5 months for CG/GG and 23.0 for CC; crude hazard ratio (HR), 0.74; 95% confidence interval (95% CI), 0.57-0.95, and adjusted HR, 0.77; 95% CI, 0.60-0.99]. This protective effect was more predominant for patients receiving surgical operation (HR, 0.58; 95% CI, 0.40-0.85; P for heterogeneity test = 0.045), along with a significant multiplicative interaction between variant genotypes and operation status (P = 0.028).

CONCLUSIONS: Our findings suggest that rs5742714 in IGF1 may be a genetic modifier for NSCLC prognosis in this Chinese population, especially among patients with surgical operation.

Author List

Zhang M, Hu Z, Huang J, Shu Y, Dai J, Jin G, Tang R, Dong J, Chen Y, Xu L, Huang X, Shen H

Author

Jing Dong PhD Assistant Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

3' Untranslated Regions
Animals
Carcinoma, Non-Small-Cell Lung
Humans
Insulin-Like Growth Factor Binding Protein 3
Insulin-Like Growth Factor I
Lung Neoplasms
Male
Middle Aged
Polymorphism, Single Nucleotide