title: Vitamin D receptor gene polymorphisms in relation to the risk of colorectal cancer in the Polish population.
abstract: The protective effect of vitamin D against several cancers including colorectal cancer is modulated by the vitamin D receptor (VDR) and its ligand, the active form of vitamin D. VDR response has been found to play a role in various genes encoding proteins involved in crucial cellular pathways. Single nucleotide polymorphisms (SNPs) of the VDR gene that modulate its activity are located in the promoter region, exons 2-9, and their vicinity and also in the 3'UTR region. Some of them have been previously studied in relation to cancer susceptibility and prognosis. The aim of our study was to investigate four polymorphisms, BsmI, ApaI, TaqI, and FokI, of the VDR gene in Polish patients with sporadic colorectal cancer and to evaluate their association with susceptibility to cancer. We found a significant association between the BsmI genotype and cancer (individuals with the bb genotype are more susceptible to cancer compared to those with other genotypes, p = 0.025, Fisher's exact test for 2 × 2 table). Also, the TT genotype at TaqI and the AA genotype at ApaI are correlated with a higher risk of cancer (p = 0.00071 and p = 1.0 × 10(-5), respectively). We found relatively strong linkage disequilibrium between the TaqI and ApaI loci (T with A and t with a, respectively). Both of these loci are associated with cancer. We do not observe any such association for the FokI polymorphism. In conclusion, a small modification in VDR expression may play a role in such a multipathway process as tumorigenesis.
authors.affiliation: Genetics Department, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Laczmanska
authors.forename: Lukasz
authors.initials: L
authors.lastname: Laczmanski
authors.forename: Marek
authors.initials: M
authors.lastname: Bebenek
authors.forename: Pawel
authors.initials: P
authors.lastname: Karpinski
authors.forename: Halina
authors.initials: H
authors.lastname: Czemarmazowicz
authors.forename: David
authors.initials: D
authors.lastname: Ramsey
authors.forename: Andrzej
authors.initials: A
authors.lastname: Milewicz
authors.forename: Maria M
authors.initials: MM
authors.lastname: Sasiadek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011044:Poland; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*; D012306:Risk
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human