Tuberc Respir Dis.  2009 Jul;67(1):8-13.

Association of Insulin Receptor Substrate-1 G972R Variant with Non-small Cell Lung Cancer Risk

• Lee CY
• Ahn CM
• Jeon JH
• Kim HJ
• Kim SK
• Chang J
• Kim SK
• Chang YS

Abstract

BACKGROUND
The insulin receptor substrate-1 (IRS-1) is the primary docking molecule for the insulin-like growth factor I receptor (IGF-IR), and is required for activation of the phosphatidylinositol 3'-kinase (PI3K) pathway. IRS-1 activation of the (PI3K) pathway regulates IGF-mediated survival, enhancement of cellular motility and apoptosis. Therefore, we attempted to ascertain whether IRS-1 genetic variations affect an individual's risk for non-small cell lung cancer (NSCLC). METHODS: Two-hundred and eighteen subjects, either diagnosed with NSCLC or control subjects, were matched by age, gender and smoking status. Genomic DNA from each subject was amplified by PCR and analyzed according to the restriction fragment length polymorphism (RFLP) profile to detect the IRS-1 G972R polymorphism. RESULTS: The frequencies of each polymorphic variation, in the control population, were as follows: GG=103 (94.5%) and GR=6 (5.5%); for the NSCLC subjects, the genotypic frequencies were as follows: GG=106 (97.2%) and GR=3 (2.8%). We could not demonstrate statistically significant differences in the genotypic distribution between the NSCLC and the control subjects (p=0.499, Fisher's Exact test). The relative risk of NSCLC, associated with the IRS-1 G972R polymorphic variation, was 1.028 (95% CI; 0.63~9.90). In addition, we found no differences between polymorphic variants with regard to the histological subtype of NSCLC. CONCLUSION: We did not observe any noteworthy differences in the frequency of the IRS-1 G972R polymorphism in NSCLC patients, compared to control subjects. These results suggest suggesting that, in our study population, the IRS-1 G972R polymorphism does may not appear to be associated with an increased risk of NSCLC.

Keyword

Insulin receptor substrate-1; Insulin-like growth factor; Non-small cell lung cancer

MeSH Terms

Apoptosis
Carcinoma, Non-Small-Cell Lung
DNA
Genetic Variation
Humans
Insulin
Insulin Receptor Substrate Proteins
Insulin-Like Growth Factor I
Phosphatidylinositols
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Receptor, Insulin
Smoke
Smoking
DNA
Insulin
Insulin Receptor Substrate Proteins
Insulin-Like Growth Factor I
Phosphatidylinositols
Receptor, Insulin
Smoke

Figure

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  Figure 1 Sequence of exon, translation (A) and polymorphic variants (B, C) of IRS-1. Note homozygotic (G/G) (B) and heterozygotic (G/A) (C) variant of IRS-1. †IUB code name (R means nucleotide A and G). Numbering of the exon†† and amino acid residue††† was adapted from Gene Bank Acc. #NM_005544.

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  Figure 2 IRS-1 G972R polymorphic variants. The representative data from PCR-RFLP are presented in this figure. Heterozygote (G/A) is shown in lane 3 and homozygote (G/G) in lanes 2, 4 and 5. M: DNA size marker (lane 1).

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