P-220 - Genetic Polymorphism of Vitamin D Receptor BsmI, ApaI and CYP27B1, CYP24A1 genes and the risk of colorectal cancer

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Cancer Aetiology, Epidemiology, Prevention
Colon Cancer
Rectal Cancer
Translational Research
Presenter N. Forones
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors N. Forones, T. da Silva, V. Vidigal, A. Felipe, C. Pimenta, J. Oliveira
  • Unversidade Federal de Sao Paulo, Sao Paulo/BR

Abstract

Introduction

Colorectal cancer (CRC) is the fourth cause of cancer. Studies had demonstrated that Vitamin D may decrease the risk of this cancer. The synthesis of Vitamin D begin from the action of ultraviolet light on 7-dehydrocholesterol precursors, that binds to the glycoprotein VDBP, then transported to the liver and converted to 25-OH vitamin D. The conversion of the complex 25-OH vitamin D and VDBP to 1,25 (OH)2 vitamin D depends of the CYP27B1 gene product protein and the metabolization by the CYP24A1 gene product protein. The vitamin D receptor (VDR) is a protein that has the function to mediate the effects of vitamin D regulating the growth and differentiation of target tissues. SNPs of VDR as APaI, BsmI and from genes involved on Vitamin D gene metabolization as CYP24A1 and CYP27B may influence the serum levels of Vitamin D. Aim: To study the polymorphisms of VDR, APaI and BsmI and the polymorphism of Vitamin D gene metabolization CYP24A1 and CYP27B1 in colorectal cancer patients.

Methods

A case control study matched by sex and age was done. A hundred and fifty two patients with CRC and 321 controls without cancer were enrolled sequentially. The CRC patients were on treatment or in follow up. DNA was extracted from peripheral blood and the genotypes polymorphisms of BsmI and ApaI were analyzed using PCR-restriction fragment length polymorphism. The polymorphisms of CYP24A1 (rs6013897, rs158552 and rs17217119) and CYP27B1 (rs10877012) were determined by gene sequencing.

Results

Among the CRC patients, the mean age was 63 years old, 53% were men and 61% were stage II or III. The heterozygous genotype or the association of heterozygous and homozygous mutated genotype of ApaI increased the risk of CRC (p = 0.048). The heterozygous genotype of the SNP rs10877012 of CYP27B1 in males also increased the risk of CRC in 2.04 times. No relationship was found between the distribution of the others SNPs. The multivariate analysis demonstrated that the heterozygous genotypes of the SNPs CYP24A1 (rs6013897 and rs158552) increased the risk of CRC. At the rs17217119, AA and GG increased the risk in 3.46 (p = 0.005) and 3.79 (p = 0.015) compared to the AG. For CYP27B1, the GT genotype also increased the risk of cancer in 2.17 times compared to GG and TT genotypes (p = 0.004).

Conclusion

The heterozygous genotype of VDR ApaI or the association of the heterozygous with the mutated homozygous increased the risk of colorectal cancer. The SNPs of CYP24A1 (rs6013897, 158552, 17217119) and CYP27B1 (rs10877012) in the multivariate analysis also had been correlated to a higher risk of this cancer.