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An exon variant in insulin receptor gene is associated with susceptibility to colorectal cancer in women

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Tumor Biology

Abstract

Given the role of insulin resistance in colorectal cancer (CRC), we explored whether genetic variants in insulin (INS), insulin receptor (INSR), insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), insulin-like growth factor 1 (IGF1), and insulin-like growth factor binding protein 3 (IGFBP3) genes were associated with CRC risk. A total of 600 subjects, including 261 cases with CRC and 339 controls, were enrolled in this case-control study. Six polymorphisms in INS (rs689), INSR (rs1799817), IRS1 (rs1801278), IRS2 (rs1805097), IGF1 (rs5742612), and IGFBP3 (rs2854744) genes were genotyped using PCR-RFLP method. No significant difference was observed for INS, INSR, IRS1, IRS2, IGF1, and IGFBP3 genes between the cases and controls. However, the INSR rs1799817 “TT + CT” genotype and “CT” genotype compared with “CC” genotype occurred more frequently in the women with CRC than women controls (P = 0.007; OR = 1.93, 95 %CI = 1.20–3.11 and P = 0.002, OR = 2.15, 95 %CI = 1.31–3.53, respectively), and the difference remained significant after adjustment for confounding factors including age, BMI, smoking status, NSAID use, and family history of CRC (P = 0.018; OR = 1.86, 95 %CI = 1.11-3.10 and P = 0.004, OR = 2.18, 95 %CI = 1.28–3.71, respectively). In conclusion, to our knowledge, this study indicated for the first time that the INSR rs1799817 TT + CT genotype and CT genotype compared with the CC genotype had 1.86-fold and 2.18-fold increased risks for CRC among women, respectively. Furthermore, this finding is in line with previous studies which found significant associations between other variants of the INSR gene and CRC risk. Nevertheless, further studies are required to confirm our findings.

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Acknowledgments

The authors are grateful to all the subjects for participating. This work was supported by a grant from Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences.

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Authors and Affiliations

  1. Department of Cancer, Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Velenjak, Shahid Chamran Highway, Tehran, 1985711151, Iran

    Touraj Mahmoudi, Khatoon Karimi, Negar Karimi, Hesamodin Dolatmoradi, Maral Arkani & Mohammad Reza Zali

  2. Cancer Genetics Department, Breast Cancer Research Center (BCRC), ACECR, Tehran, Iran

    Keivan Majidzadeh-A

  3. Department of Physiology, School of Medicine, Qom University of Medical Sciences, Qom, Iran

    Hamid Farahani

  4. Internal Medicine Department, Semnan University of Medical Sciences, Semnan, Iran

    Reza Dabiri & Hossein Nobakht

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  1. Touraj Mahmoudi
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  2. Keivan Majidzadeh-A
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Correspondence to Touraj Mahmoudi.

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Mahmoudi, T., Majidzadeh-A, K., Karimi, K. et al. An exon variant in insulin receptor gene is associated with susceptibility to colorectal cancer in women. Tumor Biol. 36, 3709–3715 (2015). https://doi.org/10.1007/s13277-014-3010-x

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  • DOI: https://doi.org/10.1007/s13277-014-3010-x

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