Abstract B44: Vitamin D receptor Fok1 gene polymorphisms are associated with colorectal cancer among African American and Hispanic participants
Authors: Sarkissyan Marianna , Wu Yanyuan , Chen Zujian , Mishra Dhruva , Vadgama Jaydutt V. 
Published: May 2015

Background: Vitamin D plays a role in cancer and acts through the vitamin D receptor (VDR). There is a dearth of information on VDR gene polymorphisms and colorectal cancer among African-American and other underrepresented groups who also have hypovitaminosis D. This study examines whether VDR SNPs, single nucleotide gene polymorphisms (Fok1, Bsm1, Apa1, and Taq1), are associated with colorectal cancer in African-American and Hispanic study participants.

Methods: DNA for genotyping was extracted from blood collected from N=378 participants (N=78 colorectal cancer patients (Cases), N=230 non-cancer subjects with no polyps (Controls w/o polyps), and N=70 non-cancer subjects with polyps (Controls w/polyp). A total of N = 149 (39.4%) participants self-identified as African-American, N = 212 (56.1%) as Hispanic/Latino, N = 9 (2.4%) as Caucasian, and N = 8 (2.1%) as Asian. The four polymorphic SNPs in VDR (FokI, BsmI, TaqI and ApaI) were assessed using the PCR-RFLP method.

Results: There was a significant association of the VDR-Fok1 FF genotype with colorectal cancer Cases (OR=2.9; P=0.036) when compared with Controls w/o polyps. The most common VDR-Fok1 genotype in the overall study population was the FF genotype (46%). However, upon breakdown by ethnicity, the FF was the most common in African-American participants (61%), and the Ff was most common in Hispanic/Latino participants (49%). When the association was assessed in a multivariate model adjusting for ethnicity, gender, age, BMI, and diagnosis, there was no significant association with any VDR polymorphism and colorectal cancer Cases (P&gt;0.05). There was also an association of the VDR-Fok1 polymorphism with metastasis (P=0.011), but not tumor size, lymph node involvement, or Duke Stage (P&gt;0.05). The other three polymorphic variants of VDR (BsmI, TaqI and ApaI) were not associated with colorectal cancer.

Conclusions: This study suggests that genetic variation at the VDR locus, in particular VDR-FokI SNPs, may influence colorectal cancer risk in the present underrepresented patient cohort. Specifically, the FF genotype is associated with Cases and was more prevalent in African-American participants, and may contribute to cancer health disparities. Additional studies are warranted to examine whether the VDR-Fok1 polymorphism assessed in combination with vitamin D levels may provide better insights into the role of VDR polymorphisms in risk and outcome from colorectal cancer.

Citation Format: Marianna Sarkissyan, Yanyuan Wu, Zujian Chen, Dhruva Mishra, Jaydutt V. Vadgama. Vitamin D receptor Fok1 gene polymorphisms are associated with colorectal cancer among African American and Hispanic participants. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B44. doi:10.1158/1538-7755.DISP13-B44