Skip to main content
SpringerLink
Log in

Start codon FokI and intron 8 BsmI variants in the vitamin D receptor gene and susceptibility to colorectal cancer

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Epidemiological evidence suggests the protective effect of vitamin D against colorectal cancer (CRC) and the polymorphisms in vitamin D receptor (VDR) gene may influence the development of CRC. In this study the possible association of VDR FokI and BsmI gene polymorphisms with CRC risk was examined. A total of 904 subjects, including 452 cases with CRC and 452 controls were enrolled in this study. All 904 subjects were genotyped for VDR FokI and BsmI gene polymorphisms by PCR-RFLP method. We observed no significant difference in genotype and allele frequencies between the cases with CRC and controls for the both FokI and BsmI polymorphisms either before or after adjustment for confounding factors including age, BMI, sex, and smoking status. Furthermore, no evidence for effect modification of the association VDR gene FokI and BsmI variants and CRC by BMI, sex, or tumor site was observed. In addition, there was no significant difference in genotype and allele frequencies between the normal weight (BMI <25 kg/m2) cases with CRC and overweight/obese (BMI ≥25 kg/m2) cases with CRC for the two SNPs. Our results do not lend support to the hypothesis that VDR gene FokI and BsmI polymorphisms are associated with the risk of CRC. However, further studies are required to confirm this finding.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Globocan: IARC International Agency for Research on Cancer

  2. Martinez ME, Giovannucci EL, Golditz GA, Stampfer DJ, Hunter FE, Speizer A, Wing A, Willett WC (1996) Calcium, vitamin D, and the occurrence of colorectal cancer among women. J Natl Cancer Inst 88:1375–1382

    Article  PubMed  CAS  Google Scholar 

  3. Grant WB, Garland CE (2003) Vitamin D as a risk reduction factor for colorectal cancer. Am Fam Physician 67:465

    PubMed  Google Scholar 

  4. 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

    Article  PubMed  CAS  Google Scholar 

  5. 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 24:185–196

    Article  PubMed  CAS  Google Scholar 

  6. Tong WM, Kallay E, Hofer H, Hulla W, Manhardt T, Peterlik M, Cross HS (1998) Growth regulation of human colon cancer cells by mutual modulation of receptor expression. Eur J Cancer 34:2119–2125

    Article  PubMed  CAS  Google Scholar 

  7. Valdivielso J, Fernandez E (2006) Vitamin D receptor polymorphisms and diseases. Clin Chim Acta 371:1–12

    Article  PubMed  CAS  Google Scholar 

  8. Bouillon R, Eelen G, Verlinden L, Mathieu C, Carmeliet G, Verstuyf A (2006) Vitamin D and cancer. J Steroid Biochem Mol Biol 102:156–162

    Article  PubMed  CAS  Google Scholar 

  9. Palmer HG, Gonzalez-Sancho JM, Espada J, Berciano MT, Puig I, Baulida J, Quintanilla M, Cano A, Herreros AG, Lafarga M, Munoz A (2001) Vitamin D3 promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of β-catenin signaling. J Cell Biol 154:369–387

    Article  PubMed  CAS  Google Scholar 

  10. Wong HL, Seow A, Arakawa K, Lee HP, Yu MC, Ingles SA (2003) Vitamin D receptor start codon polymorphism and colorectal cancer risk: effect modification by dietary calcium and fat in Singapore Chinese. Carcinogenesis 24:1091–1095

    Article  PubMed  CAS  Google Scholar 

  11. Slattery ML, Murtaugh M, Caan B, Ma KN, Wolff R, Samowitz W (2004) Associations between BMI, energy expenditure, VDR genotype and colon and rectal cancers (United States). Cancer Causes Control 15:863–872

    Article  PubMed  Google Scholar 

  12. Park KS, Woo M, Nam JH, Kim JC (2006) Start codon polymorphisms in the vitamin D receptor and colorectal cancer risk. Cancer Lett 237:199–206

    Article  PubMed  CAS  Google Scholar 

  13. Flugge J, Krusekopf S, Goldammer M, Osswald E, Terhalle W, Malzahn U, Roots I (2007) Vitamin D receptor haplotypes protect against development of colorectal cancer. Eur J Clin Pharmacol 63:997–1005

    Article  PubMed  Google Scholar 

  14. Kadiyska T, Yakulov T, Kaneva R, Nedin D, Alexandrova A, Gegova A, Savov A, Mitev V, Kremensky I (2007) Vitamin D and estrogen receptor gene polymorphisms and the risk of colorectal cancer in Bulgaria. Int J Colorectal Dis 22:395–400

    Article  PubMed  Google Scholar 

  15. Yaylim-Eraltan I, Ergen A, Arikan S, Okay E, Ozturk O, Bayrak S, Isbir T (2007) Investigation of the VDR gene polymorphisms association with susceptibility to colorectal cancer. Cell Biochem Funct 25:731–737

    Article  PubMed  CAS  Google Scholar 

  16. Ochs-Balcom HM, Cicek MS, Thompson CL, Tucker TC, Elston RC, Plummer SJ, Casey G, Li L (2008) Association of vitamin D receptor gene variants, adiposity and colon cancer. Carcinogenesis 29:1788–1793

    Article  PubMed  CAS  Google Scholar 

  17. Theodoratou E, Farrington SM, Tenesa A, McNeill G, Cetnarskyj R, Barnetson RA, Porteous ME, Dunlop MG, Campbell H (2008) Modification of the inverse association between dietary vitamin D intake and colorectal cancer risk by a FokI variant supports a chemoprotective action of vitamin D intake mediated through VDR binding. Int J Cancer 123:2170–2179

    Article  PubMed  CAS  Google Scholar 

  18. Li C, Li Y, Gao LB, Wang YY, Zhou B, Lv ML, Lu HM, Zhang L (2009) Vitamin D receptor gene polymorphisms and the risk of colorectal cancer in Chinese population. Dig Dis Sci 54:634–639

    Article  PubMed  CAS  Google Scholar 

  19. Mahmoudi T, Mohebbi SR, Pourhoseingholi MA, Fatemi SR, Zali MR (2010) Vitamin D receptor gene ApaI polymorphism is associated with susceptibility to colorectal cancer. Dig Dis Sci 55:2008–2013

    Article  PubMed  CAS  Google Scholar 

  20. Harris SS, Eccleshall TR, Gross C, Dawson-Hughes B, Feldman D (1997) The vitamin D receptor start codon polymorphism (FokI) and bone mineral density in premenopausal American Black and White women. J Bone Miner Res 12:1043–1048

    Article  PubMed  CAS  Google Scholar 

  21. Ye WZ, Reis AF, Velho G (2000) Identification of a novel Tru9I polymorphism in the human vitamin D receptor gene. J Hum Genet 45:56–57

    Article  PubMed  CAS  Google Scholar 

  22. Altmuller J, Palmer LJ, Fischer G, Scherb H, Wjst M (2001) Genome wide scans of complex human diseases: true linkage is hard to find. Am J Hum Genet 69:936–950

    Article  PubMed  CAS  Google Scholar 

  23. Nejentsev S, Godfrey L, Snook H, Rance H, Nutland S, Walker NM, Lam AC, Guja C, Ionescu-Tirgoviste C, Undlien DE, Ronningen KS, Tuomilehto-Wolf E, Tuomilehto J, Newport MJ, Clayton DG, Todd JA (2004) Comparative high-resolution analysis of linkage disequilibrium and tag single nucleotide polymorphisms between populations in the vitamin D receptor gene. Hum Mol Genet 13:1633–1639

    Article  PubMed  CAS  Google Scholar 

  24. Gross C, Musiol IM, Eccleshall TR, Malloy PJ, Feldman D (1996) The presence of a polymorphism at the translation initiation site of the vitamin D receptor gene is associated with low bone mineral density in postmenopausal Mexican-American women. J Bone Miner Res 11:1850–1855

    Article  PubMed  CAS  Google Scholar 

  25. Whitfield GK, Remus LS, Jurutka PW, Zitzer H, Oza AK, Dang HT, Haussler CA, Galligan MA, Thatcher ML, Encinas Dominquez C, Haussler MR (2001) Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Mol Cell Endocrinol 177:145–159

    Article  PubMed  CAS  Google Scholar 

  26. Arai H, Miyamoto K, Taketani Y, Yamamoto H, Iemori Y, Morita K, Tonai T, Nishisho T, Mori S, Takeda E (1997) A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women. J Bone Miner Res 12:915–921

    Article  PubMed  CAS  Google Scholar 

  27. Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG (2001) Replication validity of genetic association studies. Nat Genet 29:306–309

    Article  PubMed  CAS  Google Scholar 

  28. Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN (2003) Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet 33:177–182

    Article  PubMed  CAS  Google Scholar 

  29. Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, Sambrook PN, Eisman JA (1994) Prediction of bone density from vitamin D receptor alleles. Nature 367:284–287

    Article  PubMed  CAS  Google Scholar 

  30. Kinyamu HK, Gallagher JC, Knezetic JA, DeLuca HF, Prahl JM, Lanspa SJ (1997) Effect of vitamin D receptor genotypes on calcium absorption, duodenal vitamin D receptor concentration and serum 1,25 dihydroxyvitamin D levels in normal women. Calcif Tissue Int 60:491–495

    Article  PubMed  CAS  Google Scholar 

  31. Moncharla H, Butch AW, Pappas AA, Flick JT, Weinstein RS, De Togni P, Jilka RL, Roberson PK, Parfitt AM, Manolagas SC (1997) Quantification of vitamin D receptor mRNA by competitive polymerase chain reaction in PBMC: lack of correspondence with common allelic variants. J Bone Miner Res 12:726–733

    Article  Google Scholar 

  32. Gross C, Musiol IM, Eccleshall TR, Malloy PJ, Feldman D (1998) Vitamin D receptor gene polymorphisms: analysis of ligand binding and hormone responsiveness in cultured skin fibroblasts. Biochem Biophys Res Commun 242:467–473

    Article  PubMed  CAS  Google Scholar 

  33. Whitfield GK, Remus LS, Jurutka PW, Zitzer H, Oza AK, Hope T, Dang HTL, Haussler CA, Galligan MA, Thatcher ML, Dominguez CE, Haussler MR (2000) Are human vitamin D receptor gene polymorphisms functionally significant? In: Norman AW, Bouillon R, Thomasset M (eds) Vitamin D endocrine system: structural, biological genetic and clinical aspects. University of California, Riverside, pp 817–823

    Google Scholar 

  34. Chudek J, Karkoszka H, Schmidt-Gayk H, Ritz E, Kokot F (2000) Plasma parathyroid hormone, phosphatemia and vitamin D receptor genotype: are they interrelated? J Nephrol 13:54–58

    PubMed  CAS  Google Scholar 

  35. Flugge J, Laschinski G, Roots I, Krusekopf S (2009) Vitamin D receptor poly (A) microsatellite and colorectal cancer risk in Caucasians. Int J Colorectal Dis 24:171–175

    Article  PubMed  Google Scholar 

  36. Feskanich D, Hunter DJ, Willett WC, Hankinson SE, Hollis BW, Hough HL, Kelsey KT, Golditz GA (1998) Vitamin D receptor genotype and the risk of bone fractures in women. Epidemiology 9:535–539

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank all patients and healthy blood donors for providing blood samples. This work was supported by a grant from the Research Center of Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences.

Author information

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, Khatoon Karimi, Seyed Reza Mohebbi, Seyed Reza Fatemi & Mohammad Reza Zali

Authors
  1. Touraj Mahmoudi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Khatoon Karimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seyed Reza Mohebbi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seyed Reza Fatemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammad Reza Zali
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Touraj Mahmoudi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mahmoudi, T., Karimi, K., Mohebbi, S.R. et al. Start codon FokI and intron 8 BsmI variants in the vitamin D receptor gene and susceptibility to colorectal cancer. Mol Biol Rep 38, 4765–4770 (2011). https://doi.org/10.1007/s11033-010-0613-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-010-0613-1

Keywords

Search

Navigation