PLoS One. 2016 Jun 16;11(6):e0155236. doi: 10.1371/journal.pone.0155236. eCollection 2016.

Association of Vitamin D Receptor Gene Polymorphisms with Colorectal Cancer in a Saudi Arabian Population.

Alkhayal KA¹, Awadalia ZH¹, Vaali-Mohammed MA¹, Al Obeed OA¹, Al Wesaimer A², Halwani R³, Zubaidi AM¹, Khan Z⁴, Abdulla MH¹.

Author information

1: Colorectal Research Chair, Department of Surgery, King Khalid University hospital, College of medicine, King Saud University, Riyadh, Saudi Arabia.
2: Prince Sultan Military Medical City, Department of internal medicine, Riyadh, Saudi Arabia.
3: Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
4: Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.

Abstract

BACKGROUND:

Vitamin D, causally implicated in bone diseases and human malignancies, exerts its effects through binding to the vitamin D receptor (VDR). VDR is a transcription factor modulating the expression of several genes in different pathways. Genetic variants in the VDR gene have been associated with several cancers in different population including colorectal cancer.

OBJECTIVE:

To assess the association of VDR gene polymorphisms in relation with colorectal cancer (CRC) in a Saudi population.

METHODS:

The polymorphisms of VDR gene (BsmI, FokI, ApaI and TaqI) were analyzed by the polymerase chain reaction amplification of segments of interest followed by Sanger sequencing. One hundred diagnosed CRC patients and 100 healthy control subjects that were age and gender matched were recruited.

RESULTS:

We did not observe significant association of any of the four VDR polymorphisms with colorectal cancer risk in the overall analysis. Although not statistically significant, the AA genotype of BsmI conferred about two-fold protection against CRCs compared to the GG genotype. Stratification of the study subjects based on age and gender suggests statistically significant association of CRC with the 'C' allele of ApaI in patients >57 years of age at disease diagnosis and BsmI polymorphism in females. In addition, statistically significant differences were observed for the genotypic distributions of VDR-BsmI, ApaI and TaqI SNPs between Saudi Arabian population and several of the International HapMap project populations.

CONCLUSION:

Despite the absence of correlation of the examined VDR polymorphisms with CRCs in the combined analysis, ApaI and BsmI loci are statistically significantly associated with CRC in elderly and female patients, respectively. These findings need further validation in larger cohorts prior to utilizing these SNPs as potential screening markers for colorectal cancers in Saudi population.