Abstract 1278: Vitamin D receptor Fok1 gene polymorphisms may be associated with CRC among African American and Hispanic participants
Authors: Sarkissyan Marianna , Wu Yanyuan , Chen Zuijan , Mishra Dhruva , Sarkissyan Suren , Giannikopoulos Ioannis , Vadgama Jaydutt V. 
Published: May 2015

Background: The vitamin D pathway plays a significant role through the vitamin D receptor (VDR) in cancer tumorogenesis. Interestingly, although African Americans have the lowest levels of vitamin D serum levels, vitamin D supplementation has not yielded significant improvement in cancer risk and outcome. Gene polymorphisms in VDR may play a role. There is lack of information on VDR gene polymorphisms and colorectal cancer (CRC) among underrepresented ethnic groups. Hence, this study is among the first to examine whether VDR SNPs, single-nucleotide-gene-polymorphisms, are associated with CRC in predominately African American and Hispanic study participants.

Methods: A total of 378 participants were included in the study with 78 CRC patients and 300 non-CRC participants. Forty percent of participants were African American, 56% were Hispanic/Latino, and the remainder of participants self-identified as Caucasian or Asian. The four polymorphic SNPs in VDR - FokI (rs2228570), BsmI (rs1544410), TaqI (rs731236) and ApaI (rs7975232) - were genotyped by polymerase chain reaction and restriction fragment length polymorphism methods. Statistical Analysis was performed by using SPSS software.

Results: There was a significant difference in the distribution of the VDR-Fok1 and VDR-Apa1polymorphisms between African American and Hispanic participants (P=0.006 and 0.009, respectively). Furthermore, the VDR-Fok1 FF genotype was associated with CRC (OR=2.9; P=0.036) when compared with Controls without polyps. Upon breakdown by ethnicity, the FF genotype was most common in African American participants (61%), and the Ff genotype was 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&gt;0.05). The other three polymorphic variants of VDR (BsmI, TaqI and ApaI) were not associated with CRC in any of the analyses.

Conclusions: This study suggests that genetic variation of the VDR-FokI SNPs may influence CRC risk, particularly in African American cohorts. These findings suggest the potential need to screen for VDR polymorphisms in conjunction with screening vitamin D serum levels. As a potentially modifiable risk factor, vitamin D and the VDR mediated axis may be a point of significant interventional opportunity to effectively reduce CRC risk, with the overarching goal to reduce cancer health disparities.

Citation Format: Marianna Sarkissyan, Yanyuan Wu, Zuijan Chen, Dhruva Mishra, Suren Sarkissyan, Ioannis Giannikopoulos, Jaydutt V. Vadgama. Vitamin D receptor Fok1 gene polymorphisms may be associated with CRC among African American and Hispanic participants. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1278. doi:10.1158/1538-7445.AM2014-1278