Insulin receptor substrate-2 gene polymorphism: is it associated with endometrial cancer?
OBJECTIVE
The G1057D polymorphism in the insulin receptor substrate-2 (IRS-2) gene has been reported to be associated with insulin resistance, obesity and type 2 diabetes. However little is known about its possible association with cancer. To investigate this association, we determined the distribution of its genotypes and frequency of alleles in endometrial cancer patients.


METHODS
The study population consisted of 184 subjects: 44 patients with endometrial cancer and 140 controls without cancer. All the patients were primarily treated with surgical intervention. DNA was extracted from the leucocytes by high pure polymerase chain reaction (PCR) template preparation kit. Genetic polymorphism of IRS-2 G1057D was detected by using PCR-based restriction fragment-length polymorphism.


RESULTS
For IRS-2 G1057D polymorphism, there was a significant difference in genotype distribution and allele frequency between endometrial cancer patients and controls (p < 0.001). The risk for endometrial cancer was 4.87 times higher in the individuals with the IRS-2 DD genotype compared to the GG genotype [95% confidence interval (CI): 1.74-13.63 p = 0.003]. Also individuals with the IRS-2 D allele had a significantly higher risk of endometrium cancer compared with individuals with the IRS-2 G allele, with a relative risk of 2.23 (95% CI: 1.36-3.67, p = 0.001) for cases compared with population controls.


CONCLUSIONS
These results suggest that IRS-2 G1057D polymorphism may be associated with endometrial cancer.
Cayan
Filiz
F
Departments of Obstetrics and Gynecology, University of Mersin School of Medicine, Mersin, Turkey. filizcayan@yahoo.com
Tok
Ekrem
E
Aras-Ateş
Nurcan
N
Ayaz
Lokman
L
Akbay
Esen
E
Gen
Ramazan
R
Karakaş
Sevim
S
Dilek
Saffet
S
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004247:DNA / Q000097:blood; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length
C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D004247:DNA