Dataset Information

Association of vitamin D receptor gene variants, adiposity and colon cancer.

ABSTRACT: Vitamin D receptor (VDR) gene variants have been variably associated with risk of colon cancer in epidemiologic studies. We sought to further clarify the relationship between colon cancer and three single-nucleotide polymorphisms (SNPs) in the VDR gene (Cdx-2, FokI and TaqI) in a population-based case-control study of 250 incident cases and 246 controls. Colon cancer cases were more frequently homozygous for the Cdx-2 A allele (9.2 versus 4.1%, P = 0.06). Cdx-2 AA homozygotes were at increased risk with an unadjusted odds ratio (OR) of 2.47 [95% confidence interval (CI): 1.13-5.37, P = 0.022]; adjustment for age, sex, body mass index (BMI), non-steroidal anti-inflammatory use and family history of colorectal cancer yielded an OR of 2.27 (CI: 0.95-5.41, P = 0.065). Carriers of the FokI TT genotype were also at increased risk with an adjusted OR of 1.87 (CI: 1.03-3.38, P = 0.038). Haplotype analyses showed significant increased colon cancer risk for carriers of the Cdx-2-FokI A-T haplotype and the FokI-TaqI T-G haplotype. The three-SNP Cdx-2-FokI-TaqI (A-T-G) haplotype showed a similar association with an adjusted OR of 3.63 (CI: 1.01-13.07). A strong positive association was observed for the Cdx-2 variant among individuals with low BMI or low waist circumference. Our results suggest that genetic variation at the VDR locus, in particular Cdx-2 and FokI SNPs, may influence colon cancer risk and these associations may be modified by adiposity.

SUBMITTER: Ochs-Balcom HM

PROVIDER: S-EPMC2722851 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Association of vitamin D receptor gene variants, adiposity and colon cancer.

Ochs-Balcom Heather M HM Cicek Mine S MS Thompson Cheryl L CL Tucker Thomas C TC Elston Robert C RC J Plummer Sarah S Casey Graham G Li Li L

Carcinogenesis 20080714 9

Vitamin D receptor (VDR) gene variants have been variably associated with risk of colon cancer in epidemiologic studies. We sought to further clarify the relationship between colon cancer and three single-nucleotide polymorphisms (SNPs) in the VDR gene (Cdx-2, FokI and TaqI) in a population-based case-control study of 250 incident cases and 246 controls. Colon cancer cases were more frequently homozygous for the Cdx-2 A allele (9.2 versus 4.1%, P = 0.06). Cdx-2 AA homozygotes were at increased r ...[more]

PMID: 18628249

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Project description:BACKGROUND:Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-age women. Multiple susceptible gene as well as environmental factors and their interaction each other are contributed to the PCOS risk. Several case-control studies have researched the associations of the vitamin D receptor gene (VDR) polymorphisms with PCOS susceptibility, but the jury is still out. Here, we carried out a meta-analysis to clarify polymorphisms between ApaI (C/A) (rs7975232), BsmI (G/A) (rs1544410), FokI (C/T) (rs10735810), TaqI (T/C) (rs731236) and Tru9I (G/A) (rs757343) in the VDR gene and PCOS susceptibility based on relative lager sample size. METHODS:English database of PubMed and Embase, and Chinese database of Wanfang and China National Knowledge Infrastructure (CNKI) databases were retrivaled for the relationship between VDR gene variates and PCOS susceptibility published before 31th, May 2018. Crude odds ratios (ORs) and its 95% confidence intervals (95% CIs) in different comparisons were used to detected the strength of the association. All the statistical analyses of the present meta-analysis were performed by STATA version 12.0 software. RESULTS:Totally, 3587 (PCOS group 1922; control group 1665) participants from 13 studies were included which met our inclusion criteria. A statistically significant association between VDR ApaI (rs7975232) polymorphism and PCOS susceptibility (C vs. A: OR?=?1.19, 95%CI?=?1.06~1.34, P?=?0.004) was found in the overall population. After stratified by ethnicity, we showed that there is a significant association between VDR ApaI (rs7975232) polymorphism and susceptibility to PCOS in the Asian (C vs. A: OR?=?1.21, 95%CI?=?1.04~1.42, P?=?0.016) population, but this association was not found in the Caucasian population. Additionally, a significant relationship between VDR BsmI (rs1544410) variates with PCOS susceptibility in the Asian (G vs. A: OR?=?1.27, 95%CI?=?1.06~1.53, P?=?0.011) population, but this association was not found in the Caucasian population. We didn't find any association between VDR FokI (rs2228570), VDR TaqI (rs731236), VDR Tru9I (rs757343) and PCOS susceptibility in the overall and the subgroup populations. CONCLUSIONS:Our findings demonstrated that VDR ApaI (rs7975232) and VDR BsmI (rs1544410) polymorphisms are correlated with susceptibility to PCOS in the Asian population and VDR TaqI (rs731236), VDR FokI (rs2228570), VDR Tru9I (rs757343) did not reveal a relationship with the PCOS susceptibility.

Project description:Vitamin D deficiency has been associated with a multitude of disorders including diabetes, defective insulin secretion as well as rickets and poor bone health. Vitamin D is also a concern during childhood and adolescence and has been reported in girls from South Brazil. We determined the prevalence of vitamin D deficiency in girls from South Brazil and investigated whether the genotypic distribution of the BsmI, ApaI and TaqI polymorphisms of the VDR gene and their haplotypes were associated with vitamin D levels.Cross-sectional study including 234 apparently healthy girls aged 7 to 18 years. Height and weight were measured for calculation of body mass index (BMI) percentiles for age. Plasma levels of 25-hydroxyvitamin D [25(OH)D] were assessed. Participants were genotyped for ApaI (rs7975232), TaqI (rs731236), and BsmI (rs1544410) SNPs.The median and interquartile range (25-75%) of BMI percentile was 62.0 (33.3 - 84.9). The frequency of overweight/obesity was 24.9%. Circulating levels of 25(OH)D (? 30 ng/mL) were adequate in 9.4%; insufficient in 54.3% (20-29 ng/mL); and deficient in 36.3% (< 20 ng/mL). Genotype frequencies were GG = 47.0%, GA = 41.5%, and AA = 11.5% for BsmI; GG = 16.7%, GT = 52.6%, and TT = 30.8% for ApaI; TT = 46.2%, TC = 44.9% and CC = 9.0% for TaqI. Genotypes with no gene variance (ancestral wild genotype) of BsmI (GG vs. GA + AA, two-tailed Student's t-test p < 0.001), ApaI (GG vs. GT + TT, two-tailed Student's t-test p = 0.031) and TaqI (TT vs. TC + CC, two-tailed Student's t-test p = 0.005) SNPs and the GGT haplotype (two-tailed Student's t-test p = 0.036) were significantly associated with lower 25(OH)D levels.25-hydroxyvitamin D deficiency and insufficiency were highly prevalent in this sample. The BsmI, ApaI and TaqI wild variants of the VDR gene, as well as the GGT haplotype, were associated with lower vitamin D levels, suggesting that VDR gene polymorphisms could be linked to higher susceptibility to vitamin D deficiency in a sub-population of children and adolescents.

Dataset Information

Association of vitamin D receptor gene variants, adiposity and colon cancer.

Publications

Association of vitamin D receptor gene variants, adiposity and colon cancer.

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