Vitamin D receptor FokI gene polymorphisms may be associated with colorectal cancer among African American and Hispanic participants

Abstract

BACKGROUND: Vitamin D plays a role in cancer tumorogenesis and acts through the vitamin D receptor (VDR). Although African Americans have the lowest serum vitamin D levels, supplementation has not yielded a significant improvement in cancer. Gene polymorphisms in VDR may play a role. There is a dearth of information on VDR gene polymorphisms and colorectal cancer (CRC) among under-represented ethnic groups. In this study, the authors examined whether VDR gene single nucleotide polymorphisms (SNPs) were associated with CRC in predominately African American and Hispanic study participants. METHODS: Blood samples were collected from 378 participants, including a group of 78 patients with CRC (cases), a group of 230 noncancer participants without polyps (controls without polyps), and a group of 70 noncancer participants with polyps (controls with polyps). The 4 polymorphic SNPs in VDR (FokI, BsmI, TaqI, and ApaI) were assessed using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: There was a significant association of the VDR-FokI FF genotype with CRC cases (odds ratio, 2.9; P 5.036) compared with the controls without polyps. The most common VDR-FokI genotype in the overall study population was the FF genotype (46%). However, upon breakdown by ethnicity, the FF genotype was the most common in African American participants (61%), and the Ff genotype was the most common in Hispanic=Latino participants (49%). When the association was assessed in a multivariate model, there was no significant association with any VDR polymorphism and CRC cases (P >.05). The other 3 polymorphic variants of VDR (BsmI, TaqI, and ApaI) were not associated with CRC. CONCLUSIONS: The results from this study suggest that genetic variation of the VDR-FokI SNPs may influence CRC risk, particularly in African American cohorts. Cancer 2014;120:1387-93.

Positive correlation between vitamin D receptor gene FokI polymorphism and colorectal cancer susceptibility in South‐Khorasan of Iran

“…In line with us Hughes et al26 could not provide any significant effect between TaqI polymorphism and susceptibility to sporadic CRC in Czech population as well. Another consistency with our study approved by Sarkissyan et al19 which they showed VDR TaqI polymorphic variants were not associated with CRC in their population. Also, Heather Ochs-Balcom et al 18 did not observe significant associations between TaqI SNP and colon cancer in their analysis.…”

Genetic Basis for Colorectal Cancer Disparities

“…Pibiri et al [21] reported that single nucleotide polymorphisms in vitamin D-related (VDR) genes could minimally affect CRC susceptibility in African Americans based on their study of 961 African American CRC cases and 838 healthy African American controls. In comparison to Hispanic Americans (a population with lower CRC risk when compared to Caucasians), Sarkissyan et al [22] evaluated the association between VDR gene single nucleotide polymorphisms (SNPs) in VDR (FokI, BsmI, TaqI, and ApaI) and CRC risk. The authors compared 78 patients with CRC (cases) with 70 patients with polyps and 230 polyp-free controls.…”

Uncovering the role of admixture in disease and drug response: Association of hepatocyte gene expression and DNA methylation with African Ancestry in African Americans

“…Additionally, VDR single nucleotide polymorphisms (SNPs) have been implicated in CVDs and various cancer susceptibilities in AAs (Beydoun et al, 2018;Beydoun et al, 2017;Y. C. Li, 2013;Mishra et al, 2013;Sarkissyan et al, 2014). Our findings suggest that VDR upregulation may ameliorate some of the effect of lower plasma 1,25(OH)2D levels, while SNPs within VDR have profound effects because they exacerbate an already deficient vitamin D environment in AAs.…”