Gly972Arg variant of insulin receptor substrate 1 gene and colorectal cancer risk in overweight/obese subjects.
BACKGROUND
Given the major role of obesity and insulin resistance (IR) in colorectal cancer (CRC), we investigated whether genetic variants in ghrelin (GHRL), resistin (RETN) and insulin receptor substrate 1 (IRS1) were associated with CRC risk.


METHODS
This study was conducted as a case-control study, and 750 subjects, including 438 controls and 312 patients with CRC, were enrolled and genotyped using the PCR-RFLP method.


RESULTS
No significant differences were observed for GHRL (rs696217), RETN (rs3745367) and IRS1 (rs1801278, Gly972Arg or G972R) gene variants between the cases and controls. However, the IRS1 G972R R allele compared with the G allele and the G972R RR+GR genotype compared with the GG genotype appeared to be markers of decreased CRC susceptibility in the overweight/obese subjects (p = 0.024; odds ratio [OR] = 0.42, 95% confidence interval [95% CI], 0.20-0.91; and p = 0.048; OR = 0.42, 95% CI, 0.17-0.99, respectively). Furthermore, the R allele and RR+GR genotype were also associated with decreased risks for obesity in the patients with CRC (p = 0.007; OR = 0.35, 95% CI, 0.15-0.77; and p = 0.015; OR = 0.35, 95% CI, 0.15-0.72, respectively).


CONCLUSIONS
In accordance with previous studies, our findings suggest that the IRS1 G972R R allele and RR+GR genotype have protective effects for CRC in overweight/obese patients and for obesity in patients with CRC. Nevertheless, further studies are required to confirm these findings.
Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran - Iran.|Cancer Genetics Department, Breast Cancer Research Center (BCRC), ACECR, Tehran - Iran.
Touraj
T
Mahmoudi
Cancer Genetics Department, Breast Cancer Research Center (BCRC), ACECR, Tehran - Iran.
Keivan
K
Majidzadeh-A
Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran - Iran.
Khatoon
K
Karimi
Department of Physiology, School of Medicine, Qom University of Medical Sciences, Qom - Iran.
Hamid
H
Farahani
Internal Medicine Department, Semnan University of Medical Sciences, Semnan - Iran.
Reza
R
Dabiri
Internal Medicine Department, Semnan University of Medical Sciences, Semnan - Iran.
Hossein
H
Nobakht
Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil - Iran.
Asadollah
A
Asadi
Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran - Iran.
Negar
N
Karimi
Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran - Iran.
Maral
M
Arkani
Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran - Iran.
Mohammad Reza
MR
Zali
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics*; D015992:Body Mass Index; D015179:Colorectal Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000235:genetics* / Q000473:pathology; D050177:Overweight / Q000150:complications / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D014408:Biomarkers, Tumor; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins