Abstract
The physiological role of vitamin D extends beyond bone health and calcium-phosphate homeostasis to effects on cancer risk, mainly for colorectal cancer. Vitamin D may have an anticancer effect in colorectal cancer mediated by binding of the active form 1,25(OH)2D to the vitamin D receptor (VDR). The Taq1 VDR gene polymorphism, a C-to-T base substitution (rs731236) in exon 9 may influence its expression and function. The aim of this study was to determine the 25(OH)D vitamin D level and to investigate the association between circulating vitamin D level and Taq1VDR gene polymorphism among Jordanian colorectal cancer patients. This case control study enrolled ninety-three patients and one hundred and two healthy Jordanian volunteers from AL-Basheer Hospital/Amman (2012-2013). Ethical approval and signed consent forms were obtained from all participants before sample collection. 25(OH)D levels were determined by competitive immunoassay Elecsys (Roche Diagnostic, France). DNA was extracted (Promega, USA) and amplified by PCR followed by VDR Taq1 restriction enzyme digestion. The genotype distribution was evaluated by paired t-test and chi-square. Comparison between vitamin D levels among CRC and control were assessed by odds ratio with 95% confidence interval. The vitamin D serum level was significantly lower among colorectal cancer patients (8.34 ng/ml) compared to the healthy control group (21.02 ng/ml). Patients deficient in vitamin D (less than 10.0 ng/ml) had increased colorectal cancer risk 19.2 fold compared to control. Only 2.2% of CRC patients had optimal vitamin D compared to 23.5% among healthy control. TT, Tt and tt Taq1 genotype frequencies among CRC cases was 35.5%, 50.5% and 14% compared to 43.1%, 41.2% and 15.7% among healthy control; respectively. CRC patients had lower mean vitamin D level among TT (8.91 ± 4.31) and Tt (9.15 ± 5.25) genotypes compared to control ((21.3 ± 8.31) and (19.3 ± 7.68); respectively. There is significant association between low 25(OH)D serum level and colorectal cancer risk. The VDRTaq1 polymorphism was associated with increased colorectal cancer risk among patient with VDRTaq1 TT and Tt genotypes. Understanding the functional mechanism of VDRTaq1 TT and Tt may provide a strategy for colorectal cancer prevention and treatment.
Highlights
Colorectal cancer (CRC) is a major public health problem; it is the third most common cancer in men and the second in women worldwide (Kang et al, 2011) that arises from abnormal growth in the lining or epithelium of the colon, rectum or appendix (Bia et al, 2012)
Vitamin D may have an anticancer effect in colorectal cancer mediated by binding of the active form 1,25(OH)2D to the vitamin D receptor (VDR)
Ethical approval and signed consent forms were obtained from all participants before sample collection. 25(OH)D levels were determined by competitive immunoassay Elecsys (Roche Diagnostic, France)
Summary
Colorectal cancer (CRC) is a major public health problem; it is the third most common cancer in men and the second in women worldwide (Kang et al, 2011) that arises from abnormal growth in the lining or epithelium of the colon, rectum or appendix (Bia et al, 2012). VDR is a protein consists of 427 amino acids, with a molecular weight of about forty eight KDa (Bouillon et al, 2008) It is an endocrine member of nuclear receptor (NRs) super-family which can enhance gene transcription and regulate gene expression in a ligandinducible manner (Deeb et al, 2007). Many genetic studies evaluated the association between Taq VDR gene polymorphisms and colorectal cancer (Slattery et al, 2001; Peters et al, 2004; Flugge et al, 2007; YaylimEraltan et al, 2007). No report evaluated the association between circulating vitamin D level and VDR Taq gene polymorphism among Jordanian population. The aim of this study is screen Taq VDR gene polymorphism, C to T base substitution in exon 9 among Jordanian CRC patients, to determine 25-hydroxyl vitamin D serum level among CRC patients and to compare them with healthy control
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