Abstract

Vitamin D and its cognate intracellular nuclear receptor, namely, vitamin D receptor (VDR), are involved in the regulation of a variety of body metabolic processes, immune function, and oncogenesis. A large number of studies demonstrated the association of low vitamin D levels and variations in five common single nucleotide polymorphisms (SNPs), FokI, BsmI, Tru9I, ApaI, and TaqI, with the risk of several cancers, including colorectal cancers. However, these associations vary among different populations. This case-control study was aimed at analysing whether common single-nucleotide polymorphisms (SNPs) and haplotypes of the vitamin D receptor (VDR) gene contribute to colorectal carcinogenesis in the Thai population. We enrolled 364 Thai participants from King Chulalongkorn Memorial Hospital between 2014 and 2015. Half of the participants underwent colonoscopy and showed a normal colon without polyps (control group) and another half were newly diagnosed patients with colorectal cancer (CRC) by colonoscopy during the index period, were under treatment, or were followed up at the outpatient clinic (case group). Differences in allele and genotype frequencies of five common VDR SNPs, between the case and control groups, were the primary outcome measures. Differences in haplotype frequencies of the five SNPs between the case and control groups were the secondary outcome measures. Among the 364 participants, baseline characteristics were not significantly different between the case and control groups, except for the higher proportion of males in the CRC group. The mean vitamin D level was also not significantly different between the case and control groups (24.6 ± 9.1 vs. 25.3 ± 10.6 ng/mL, p = 0.52). None of the five VDR SNPs was associated with CRC development (p > 0.05). However, haplotype analysis of these polymorphisms demonstrated that the AGGT haplotype was associated with a decreased risk of CRC (odds ratio 0.24, 95% confidence interval 0.07-0.81, p = 0.01). The AGGT haplotype was associated with a lower risk of CRC in the Thai population. This genetic linkage might support the role of vitamin D in colorectal carcinogenesis. However, this finding requires further study within a larger population and a multivariate analysis of other established risk factors.

Highlights

  • Colorectal cancer (CRC) is one of the most common malignancies worldwide

  • As there is not enough data on the Thai population, this study was aimed at analysing whether common singlenucleotide polymorphisms (SNPs) and specific haplotypes of the vitamin D receptor (VDR) gene contribute to colorectal carcinogenesis in the Thai population

  • Most epidemiological and scientific studies have strongly suggested that vitamin D and the VDR gene may have a role in colorectal pathogenesis [22, 23] and that variations in VDR single nucleotide polymorphisms (SNPs) are associated with CRC [19]

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Summary

Introduction

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Vitamin D deficiency is one of the nutritional factors related to CRC risk. A previous epidemiologic study showed a higher prevalence of CRC in areas with low solar ultraviolet B exposure. Recent reviews, both in vitro and in vivo, suggested an association between vitamin D deficiency and an increased risk of various malignancies, including breast cancer, prostate cancer, and CRC [3, 4]. Maintaining a normal vitamin D level has been shown to reduce CRC risk [5,6,7]

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