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The −4817 G>A (rs2238136) variant of the vitamin D receptor gene: a probable risk factor for colorectal cancer

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Abstract

Vitamin D appears to have anti-tumor activities in the large bowel. Our aim was to investigate whether −4817 G>A (rs2238136) polymorphism located at 5′-untranslated region (5′-UTR) of the human vitamin D receptor (VDR) gene was associated with colorectal cancer (CRC) risk. We conducted a case–control study and VDR genotypes, determined by Bpu10I restriction endonuclease digestion of PCR-amplified DNA, were performed on 327 cases with CRC and 327 controls. The distribution of VDR −4817 G>A genotypes and alleles differed significantly between cases with CRC and controls even after adjustment for confounding factors such as age, BMI, sex, and smoking status. Individuals carrying the “AA” genotype had a 2.09-fold increased risk compared with those with “GG” genotype (P = 0.016, OR = 2.09, 95% CI = 1.15–3.78) and a 1.87-fold increased risk compared with those with “GG and GA” genotypes (P = 0.033, OR = 1.87, 95% CI = 1.05–3.33) for CRC. Furthermore, the VDR “A” allele was significantly overrepresented in cases with CRC than controls (P = 0.044; OR = 1.28, 95% CI = 1.01–1.63). Interestingly, the analysis of the SNP revealed that all these associations were stronger for women subjects than for all subjects combined. These data indicated for the first time a direct association between “AA” genotype of VDR gene −4817 G>A polymorphism and CRC, with a stronger association for female subjects. However, our findings remain to be confirmed in other populations.

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Acknowledgments

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

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Authors and Affiliations

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

    Touraj Mahmoudi, Maral Arkani, Khatoon Karimi, Akram Safaei, Fatemeh Rostami, Elham Arbabi, Mohamad Amin Pourhoseingholi, Seyed Reza Mohebbi, Sara Romani, Shohreh Almasi, Maryam Abbaszadeh & Mohammad Reza Zali

  2. Department of Biochemistry, Faculty of Medicine, Ahwaz Jondi Shapour University of Medical Sciences, Ahwaz, Iran

    Abdolrahim Nikzamir

  3. Iranian Ostomy Society, Tehran, Iran

    Mohammad Vafaei

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  1. Touraj Mahmoudi
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  2. Maral Arkani
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Correspondence to Touraj Mahmoudi.

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Mahmoudi, T., Arkani, M., Karimi, K. et al. The −4817 G>A (rs2238136) variant of the vitamin D receptor gene: a probable risk factor for colorectal cancer. Mol Biol Rep 39, 5277–5282 (2012). https://doi.org/10.1007/s11033-011-1325-x

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  • DOI: https://doi.org/10.1007/s11033-011-1325-x

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