Start codon polymorphisms in the vitamin D receptor and colorectal cancer risk

Wang

et al. 2015

Tohoku J. Exp. Med.

Vitamin D is a potential protective agent against cancer, and its activity is mediated mainly by vitamin D receptor (VDR). The FokI polymorphism (rs10735810) represents a T-to-C transition (ATG to ACG) in exon 2 of the VDR gene, and this ATG represents the translation-initiation codon, encoded by the f allele. The FokI polymorphism results in the generation of a protein shortened by three amino acids, translated from the downstream ATG codon (the F allele). We investigated the relationship between the FokI polymorphism and gastric cancer in a Chinese Han population. A total of 187 patients and 212 healthy controls were enrolled. The FokI polymorphism was detected by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. The f allele frequency was higher in patients than that in controls (51.6% and 43.6%, P < 0.05). Multivariate logistics regression analysis revealed patients with the f allele (Ff + ff) showed a higher risk of gastric cancer [odds ratio (95% confidence interval) 2.73 (1.13~4.32)]. Patients with the f allele (Ff + ff) also presented a poorly differentiated type of gastric cancer (P < 0.05) and higher levels of C-reactive protein on admission than the FF group (5.5 ± 2.4 mg/L vs. 3.4 ± 1.3 mg/L, P < 0.05). Here, we show an association between the VDR FokI polymorphism and the susceptibility to gastric cancer, which may be helpful for early detection of high-risk individuals with the f allele for gastric cancer. Conversely, the F allele may be a protective factor against gastric cancer.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

FokI Polymorphism of the Vitamin D Receptor Gene Is Associated with Susceptibility to Gastric Cancer: A Case-Control Study

Wang

et al. 2015

Tohoku J. Exp. Med.

Asian Pacific Journal of Cancer Prevention

“…If the initiating translation starts from this alternative site (thymine variant), it results in the generation of a longer VDR protein of 427 amino acids (Kostner et al, 2009). The polymorphisms in this area have been studied singly and in combination with other polymorphisms of VDR in a number of malignant and non malignant conditions (Chiu et al, 2001;Malecki et al, 2003;Park et al, 2006;Kadyska et al, 2007;Hubner et al, 2008;Neyestani et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Association of a VDR Gene Polymorphism with Risk of Colorectal Cancer in Kashmir

Rasool

Kadla²,

Khan³

et al. 2013

Roles of the vitamin D receptor in etiology of cancers, including colorectal cancer, have been repeatedly stressed in different parts of the world. A case control study aimed to evaluate the relationship between the two was therefore initiated in Kashmir, known both for its increasing incidence of gastrointestinal cancers and deficiency of micro-nutrients especially vitamin D. The study included a total of 617 subjects (312 colorectal cancer cases and 305 controls), with sampling carried out over a period of 5 years. DNA samples from the blood of the subjects were analyzed for start codon Fok I VDR polymorphism. We obtained a 1.3 fold increased risk among individuals homozygous for f variants as compared to subjects homozygous for F allele (odds ratio OR 1.3, 95%CI, 0.861-1.65). Our study also showed statistically significant results when dwelling and tumor location characteristics were stratified with Fok I polymorphism, all of which suggests a possible role of Fok I polymorphism in the etiology of CRC in Kashmir

Cancer Epidemiology, Biomarkers &Amp; Prevention

“…18). Each of the candidate SNPs were previously found associated with the risk of breast (19)(20)(21), colon (22,23), or prostate cancers (24)(25)(26) that are malignancies with possible etiologic similarities to ovarian cancer (27). The rs10735810 (FokI) is a coding nonsynonymous SNP in the translational initiation codon that has been reported to have functional significance in several in vitro studies with C (often called ''F'' allele) more effective than the T (or ''f'') allele in transactivation of the vitamin D signal (28)(29)(30).…”

Section: Introductionmentioning

confidence: 99%

Vitamin D ReceptorGene Polymorphisms and Epithelial Ovarian Cancer Risk

Lurie

Wilkens

Thompson

et al. 2007

Epidemiologic and laboratory studies support a role for the vitamin D endocrine system in ovarian carcinogenesis. The association of ovarian cancer risk with polymorphisms in the vitamin D receptor (VDR) gene, including rs10735810 (Fok I), rs11568820 (Cdx -2), rs1544410 (BsmI), rs7975232 (ApaI), rs731236 (TaqI), and BsmI-ApaI-TaqI combined genotypes, was examined among 313 women with epithelial ovarian carcinoma and 574 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. The associations of VDR polymorphisms with risk were generally inconsistent across ethnic groups. Among Caucasian women (72 cases, 148 controls), heterozygous and homozygous ApaI A allele carriers were at increased ovarian carcinoma risk compared with homozygous carriers of the ApaI a allele (OR 2.8, 95% CI 1.2-7.0 and OR 3.4, 95% CI 1.3-9.1; P trend = 0.02). Caucasian heterozygous carriers of FokI f allele were also at increased risk of ovarian carcinoma compared with homozygous carriers of the common allele (OR 2.5, 95% CI 1.3-4.8; P trend = 0.04). Among Japanese women (94 cases, 173 controls), ovarian cancer risk was significantly decreased (OR 0.5, 95% CI 0.3-0.9) among Cdx-2 A allele heterozygotes compared with homozygote G allele carriers (P trend = 0.03). Compared with the bbaaTT BsmI-ApaI-TaqI genotype, bbaATT and BBAAtt genotypes were associated with increased ovarian cancer risk in Caucasian women (OR 4.2, 95% CI 1.3-13.1 and OR 5.2, 95% CI 1.6-17.5), but not in Japanese women (OR 1.1, 95% CI 0.6-1.9 and OR 2.3, 95% CI:0.4-12.3). This investigation provides some evidence that polymorphisms in the VDR gene might influence ovarian cancer susceptibility. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2566 -71)