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Patterns of Polymorphisms in Vitamin D metabolism related genes in the genomic DNA of patients with Barrett's Esophagus and Esophageal Adenocarcinoma
Saurabh Singhal*1,2, Harit Kapoor3, Saravanan Subramanian2, Shunsuke Akimoto1, Devendra K. Agrawal2, Sumeet Mittal1
1General Surgery, Creighton university Medical Center, Omaha, NE; 2Biomedical Sciences, Creighton University, Omaha, NE; 3General Surgery, Providence Hospital and Medical Center, Southfield, MI
Introduction
Barrett's Esophagus (BE) develops in 5-10% of patients with chronic GERD and upto 5% of these patients may progress to Esophageal Adenocarcinoma (EAC). Identification of the molecular triggers of this progression is highly desirable. The Vitamin D receptor (VDR) endocrine system has emerged as an endogenous pleotropic biological cell regulator with evidence of anti-neoplastic effects on breast, colorectal and prostatic adenocarcinomas. In this stud, we assess polymorphisms in VDR and Vit-D Regulatory Cytochrome P 450 enzymes CYP27B1 and CYP24A1 in patients with BE and EAC and compare them with normal subjects.
Methodology
After IRB approval, patients with biopsy proven BE, esophageal adenocarcinoma and voluntary healthy controls were recruited. Blood samples were collected and analysed for the polymorphisms in genomic DNA for VDR (FokI, BsmI, ApaI and TaqI), CYP27B1 (Hinfl) and CYP24A1 (Hpy1881). Data was analysed for percentage of homozygous dominant/recessive or heterozygous trait for each polymorphism in each subgroup of patients.
Results
Total of 25 patients were recruited (7 controls, 5 with BE and 13 with EAC). All tested polymorphisms in BE patients showed similar trend as to controls except Fokl gene for VDR (Control:Barrett’s for various polymorphisms= BsmI BB 71.4%:80%, Apal Aa 71.4%:80%, Taql Tt 71.4%:80%, Hinfl HH 71.4%:80%, Hpy1881 YY 100%:100%). EAC patients showed marked difference in polymorphisms. Heterozygous form of Bsml (Bb) and homozygous dominant form of Fokl (FF) were strongly expressed in patients with esophageal adenocarcinoma (Bb - 84.6%, FF - 84.6%). None of the other genes showed any significant trend for carcinoma patients. Heterozygous form of Hpy1881 for CYP24A1 (Yy) was expressed in a subsets of carcinoma patients (30.8%) while it was absent in all control and BE patients.
Conclusion
Heterozygous form of Bsml (Bb) and homozygous dominant form of Fokl (FF) among VDR gene polymorphisms and heterozygous form of Hpy1881 (Yy) for CYP24A1 gene seem to be more prevalent in EAC compared to controls and BE. Further research is warranted.
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