A 3'-untranslated region polymorphism in IGF1 predicts survival of non-small cell lung cancer in a Chinese population.
OBJECTIVE
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.


METHODS
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.
Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, Nanjing, China.
Mingfeng
M
Zhang
Zhibin
Z
Hu
Jinlin
J
Huang
Yongqian
Y
Shu
Juncheng
J
Dai
Guangfu
G
Jin
Rong
R
Tang
Jing
J
Dong
Yijiang
Y
Chen
Lin
L
Xu
Xinen
X
Huang
Hongbing
H
Shen
D020413:3' Untranslated Regions; D000818:Animals; D044466:Asian People; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D020413:3' Untranslated Regions; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I