Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Lack of Associations between Vitamin D Metabolism-Related Gene Variants and Risk of Colorectal Cancer

  • Mahmoudi, Touraj (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Karimi, Khatoon (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Arkani, Maral (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Farahani, Hamid (Department of Physiology, School of Medicine, Qom University of Medical Sciences) ;
  • Nobakht, Hossein (Internal Medicine Department, Semnan University of Medical Sciences) ;
  • Dabiri, Reza (Internal Medicine Department, Semnan University of Medical Sciences) ;
  • Asadi, Asadollah (Department of Biology, Faculty of Science, University of Mohaghegh Ardabili) ;
  • Vahedi, Mohsen (Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences) ;
  • Zali, Mohammad Reza (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences)
  • Published : 2014.01.30
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: With regard to the protective effect of vitamin D against colorectal cancer (CRC), we evaluated genetic variants that might influence vitamin D metabolism: vitamin D receptor (VDR), vitamin D binding protein (GC), vitamin D 25-hydroxylase (CYP2R1), and vitamin D 25-hydroxy 1-alpha hydroxylase (CYP27B1). Materials and Methods: A total of 657 subjects, including 303 cases with CRC and 354 controls were enrolled in this case-control study. All 657 were genotyped for the four gene variants using PCR-RFLP methods. Results: In this study, no significant difference was observed for VDR (rs2238136), GC (rs4588), CYP2R1 (rs12794714), and CYP27B1 (rs3782130) gene variants in either genotype or allele frequencies between the cases with CRC and the controls and this lack of difference remained even after adjustment for age, BMI, sex, smoking status, NSAID use, and family history of CRC. Furthermore, no evidence for effect modification of the variants and CRC by BMI, sex, or tumor site was observed. Conclusions: Our findings do not support a role for VDR, GC, and CYP27B1 genes in CRC risk in our Iranian population. Another interesting finding, which to our knowledge has not been reported previously, was the lack of association with the CYP2R1 gene polymorphism. Nonetheless, our findings require confirmation and possible roles of vitamin D metabolism-related genes in carcinogenesis need to be further investigated.

Keywords

References

  1. Bu FX, Armas L, Lappe J, et al (2010). Comprehensive association analysis of nine candidate genes with serum 25-hydroxy vitamin D levels among healthy Caucasian subjects. Hum Genet, 128, 549-56. https://doi.org/10.1007/s00439-010-0881-9
  2. Bureau JP, Henry L, Baz A, Scherrer K, Chateau MT (1997). Prosomes (proteasomes) changes during differentiation are related to the type of inducer. Mol Biol Rep, 24, 57-62. https://doi.org/10.1023/A:1006856707793
  3. Dong LM, Ulrich CM, Hsu L, et al (2009). Vitamin D related genes, CYP24A1 and CYP27B1, and colon cancer risk. Cancer Epidemiol Biomarkers Prev, 18, 2540-8. https://doi.org/10.1158/1055-9965.EPI-09-0228
  4. Egan JB, Thompson PA, Vitanov MV, et al (2010). Vitamin D receptor ligands, adenomatous polyposis coli, and the vitamin D receptor FokI polymorphism collectively modulate beta-catenin activity in colon cancer cells. Mol Carcinog, 49, 337-52.
  5. Fang Y, van Meurs JB, d'Alesio A, et al (2005). Promoter and 3'-untranslated-region haplotypes in the vitamin d receptor gene predispose to osteoporotic fracture: the rotterdam study. Am J Hum Genet, 77, 807-23. https://doi.org/10.1086/497438
  6. Flugge J, Krusekopf S, Goldammer M, et al (2007). Vitamin D receptor haplotypes protect against development of colorectal cancer. Eur J Clin Pharmacol, 63, 997-1005. https://doi.org/10.1007/s00228-007-0367-4
  7. Guzey M, Kitada S, Reed JC (2002). Apoptosis induction by $1\alpha$, 25-Dihydroxyvitamin D3 in prostate cancer. Mol Cancer Ther, 1, 667-77.
  8. Hibler EA, Hu C, Jurutka PW, Martinez ME, Jacobs ET (2012). Polymorphic variation in the GC and CASR genes and associations with vitamin D metabolite concentration and metachronous colorectal neoplasia. Cancer Epidemiol Biomarkers Prev, 21, 368-75. https://doi.org/10.1158/1055-9965.EPI-11-0916
  9. Howard G, Nguyen T, Morrison N, et al (1995). Genetic influences on bone density: physiological correlates of vitamin D receptor gene alleles in premenopausal women. J Clin Endocrinol Metab, 80, 2800-5.
  10. Hughes DJ, Hlavata I, Soucek P, et al (2011). Variation in the vitamin D receptor gene is not associated with risk of colorectal cancer in the Czech Republic. J Gastrointest Cancer, 42, 149-54. https://doi.org/10.1007/s12029-010-9168-6
  11. Huncharek M, Muscat J, Kupelnick B (2009). Colorectal cancer risk and dietary intake of calcium, vitamin D, and dairy products: a meta-analysis of 26,335 cases from 60 observational studies. Nutr Cancer, 61, 47-69. https://doi.org/10.1080/01635580802395733
  12. Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG (2001). Replication validity of genetic association studies. Nat Genet, 29, 306-9. https://doi.org/10.1038/ng749
  13. Jemal A, Tiwari RC, Murray T, et al (2004). American Cancer Society (2004) Cancer statistics. CA Cancer J Clin, 54, 8-29. https://doi.org/10.3322/canjclin.54.1.8
  14. Kampman E, Slattery ML, Caan B, Potter JD (2000). Calcium, vitamin D, sunshine exposure, dairy products and colon cancer risk (United States). Cancer Causes Control, 11, 459-466. https://doi.org/10.1023/A:1008914108739
  15. Mahmoudi T, Arkani M, Karimi K, et al (2012). The-4817 G>A (rs2238136) variant of the vitamin D receptor gene: a probable risk factor for colorectal cancer. Mol Biol Rep, 39, 5277-82. https://doi.org/10.1007/s11033-011-1325-x
  16. Mahmoudi T, Karimi K, Mohebbi SR, Fatemi SR, Zali MR (2011). Start codon FokI and intron 8 BsmI variants in the vitamin D receptor gene and susceptibility to colorectal cancer. Mol Biol Rep, 38, 4765-70. https://doi.org/10.1007/s11033-010-0613-1
  17. Palmer HG, Gonzalez-Sancho JM, Espada J, et al. (2001). Vitamin D3 promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of $\beta$-catenin signaling. J Cell Biol, 154, 369-87. https://doi.org/10.1083/jcb.200102028
  18. Poynter JN, Jacobs ET, Figueiredo JC, et al (2010). Genetic variation in the vitamin D receptor (VDR) and the vitamin D-binding protein (GC) and risk for colorectal cancer: results from the Colon Cancer Family Registry. Cancer Epidemiol Biomarkers Prev, 19, 525-36. https://doi.org/10.1158/1055-9965.EPI-09-0662
  19. Sinotte M, Diorio C, Berube S, Pollak M, Brisson J (2009). Genetic polymorphisms of the vitamin D binding protein and plasma concentrations of 25-hydroxyvitamin D in premenopausal women. Am J Clin Nutr, 89, 634-40. https://doi.org/10.3945/ajcn.2008.26445
  20. Stein GS, Lian JB, Van Wijnen AJ, Stein JL (1997). The osteocalcin gene: a model for multiple parameters of skeletal-specific transcriptional control. Mol Biol Rep, 24, 185-96. https://doi.org/10.1023/A:1006803615430
  21. Woolcott CG, Wilkens LR, Nomura AM, et al (2010). Plasma 25-hydroxyvitamin D levels and the risk of colorectal cancer: The multiethnic cohort study. Cancer Epidemiol Biomarkers Prev, 19, 130-4. https://doi.org/10.1158/1055-9965.EPI-09-0475
  22. Zehnder D, Bland R, Williams MC, et al (2001). External expression of 25-hydroxyvitamin D(3)-1alpha hydroxylase. J Clin Endocrinol Metab, 86, 888-94.
  23. Zhou L, Zhang X, Chen X, et al (2012). GC Glu416Asp and Thr420Lys polymorphisms contribute to gastrointestinal cancer susceptibility in a Chinese population. Int J Clin Exp Med, 5, 72-9.

Cited by

  1. Vitamin D Receptor BsmI Polymorphism and Colorectal Cancer Risk: an Updated Analysis vol.15, pp.12, 2014, https://doi.org/10.7314/APJCP.2014.15.12.4801
  2. Single Nucleotide Polymorphisms in the Gc Gene for Vitamin D Binding Protein in Common Cancers in Thailand vol.16, pp.8, 2015, https://doi.org/10.7314/APJCP.2015.16.8.3339
  3. Association of Dietary Vitamin D and Calcium With Genetic Polymorphisms in Colorectal Neoplasia vol.20, pp.2, 2015, https://doi.org/10.15430/JCP.2015.20.2.97
  4. Vitamin D Receptor Gene Polymorphism and the Risk of Colorectal Cancer: A Nested Case-Control Study vol.11, pp.10, 2016, https://doi.org/10.1371/journal.pone.0164648
  5. Vitamin D and Cancer Risk and Mortality: State of the Science, Gaps, and Challenges vol.39, pp.1, 2017, https://doi.org/10.1093/epirev/mxx005
  6. Prospective associations between vitamin D status, vitamin D–related gene polymorphisms, and risk of tobacco-related cancers vol.102, pp.5, 2015, https://doi.org/10.3945/ajcn.115.110510