Study of Vitamin D Receptor (VDR) Gene Polymorphisms among Egyptian Cohort Patients with Different Stages of Colorectal Cancer
- 1 Clinical Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
- 2 Clinical Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
- 3 Colorectal Surgery Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
Abstract
Colorectal cancer represents the third cancer worldwide. Studies showed thatinsufficient levels of vitamin D may result in colorectal cancer. Genetic variations in genes controlling vitamin D activity would play a role in determining susceptibility to colorectal cancer. Aim of the work: to study the different genotypes of VDR polymorphisms and detect the association between serum levels of 25(OH)VitD and 1,25(OH)2VitD among sample of Egyptian patients with different stages of colorectal cancer. Methods: Ninety patients (60 with different stages of colorectal cancer and 30 patients with benign pathology of the colon) together with 30 healthy controls were examined using PCR-RFLP analysis for FokI, ApaI and TaqI polymorphisms. Results: Genotype distribution for ApaI polymorphism showed no statistically significant difference between patients (colorectal cancer and benign) and controls with p = 0.1. There was no statistically significant difference in FokI polymorphism where p = 0.26 and genotype distribution for TaqI was also insignificant with p = 0.016. The median serum level of 25(OH)VitD was low in cancer cases compared to the control group and benign cases with (p < 0.001). There was no statisticallysignificant difference of median serum level of 1,25(OH)2VitD between benign and cancer cases. There was statistically significant difference of median serum level of 25(OH)VitD and 1,25(OH)2VitD between stage I and stage II with (p = 0.004) and (p < 0.001), and between stage I and stage III with (p = 0.001)and (p < 0.001), but no statistically significant difference between stage II and III with (p = 0.514). Conclusions: There is ethnic variability in vitamin D receptor gene polymorphisms. The lack of significant association of the studied gene polymorphism in our population suggests that its association with other functionally known gene polymorphism might have a role in the pathogenesis of colorectal cancer.
- World Health Organization (2012) Cancer. Fact Sheet No. 297.
- Garland, C.F. and Garland, F.C. (1980) Do Sunlight and Vitamin D Reduce the Likelihood of Colon Cancer? International Journal of Epidemiology, 9, 227-231. http://dx.doi.org/10.1093/ije/9.3.227
- Garland, C.F., Garland, F.C. and Gorham, E.D. (1999) Calcium and Vitamin D. Their Potential Roles in Colon and Breast Cancer Prevention. Annals of the New York Academy of Sciences, 889, 107-119. http://dx.doi.org/10.1111/j.1749-6632.1999.tb08728.x
- Holt, P.R. (1999) Dairy Foods and Prevention of Colon Cancer: Human Studies. The Journal of the American College of Nutrition, 18, 379S-391S. http://dx.doi.org/10.1080/07315724.1999.10718902
- Miyamoto, K., Kesterson, R.A., Yamamoto, H., Taketani, Y., Nishiwaki, E., Tatsumi, S., Inoue, Y., Morita, K., Takeda, E. and Pike, J.W. (1997) Structural Organization of the Human Vitamin D Receptor Chromosomal Gene and Its Promoter. Molecular Endocrinology, 11, 1165-1179. http://dx.doi.org/10. 1210/mend.11.8.9951
- Whitfield, G.K., Remus, L.S., Jurutka, P.W., Zitzer, H., Oza, A.K., Dang, H.T., Haussler, C.A., Galligan, M.A., Thatcher, M.L., Encinas Dominguez, C. and Haussler, M.R. (2001) Functionally Relevant Polymorphisms in the Human Nuclear Vitamin D Receptor Gene. Molecular and Cellular Endocrinology, 177, 145-159. http://dx.doi.org/10.1016/S0303-7207(01)00406-3
- Woolcott, C.G., Wilkens, L.R., Nomura, A.M.Y., et al. (2010) Plasma 25-Hydroxyvitamin D Levels and the Risk of Colorectal Cancer: The Multiethnic Cohort Study. Cancer Epidemiology, Biomarkers & Prevention, 19, 130-134. http://dx.doi.org/10.1158/1055-9965.EPI-09-0475
- Ulrike, P. (2004) Circulating Vitamin D Metabolites, Polymorphism in Vitamin D Receptor and Colorectal Adenoma Risk. Cancer Epidemiology, Biomarkers & Prevention, 13, 546-555.
- Jenab, M. (2010) Association between Pre-Diagnostic Circulating Vitamin D Concentration and Risk of Colorectal Cancer in European Populations: A Nested Case-Control Study. BMJ, 340, b5500. http://dx.doi.org/10.1136/bmj.b5500
- Holick, M.F. (2009) Vitamin D Status: Measurement, Interpretation and Clinical Application. Annals of Epidemiology, 19, 73-78. http://dx.doi.org/10.1016/j.annepidem.2007.12.001
- Holick, M.F. (2006) High Prevalence of Vitamin D Inadequacy and Implications for Health. Mayo Clinic Proceedings, 81, 353-373. http://dx.doi.org/10.4065/81.3.353