Circulating vitamin D metabolites, polymorphism in vitamin D receptor, and colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev 13(4), 546-52

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH/DHHS, 6120 Executive Boulevard, EPS 3024, Rockville, MD 20852, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 05/2004; 13(4):546-52.
Source: PubMed


Vitamin D is a potential agent for the prevention of colorectal cancer possibly through mechanisms mediated by the vitamin D receptor (VDR). We investigated the association of circulating vitamin D metabolites and a genetic variant of the VDR gene with advanced colorectal adenoma, a precursor lesion of colorectal cancer.
Cases with advanced adenoma of the distal large bowel and gender- and ethnicity-matched controls with a negative sigmoidoscopy were randomly selected from participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. Genotype analysis of the VDR TaqI polymorphism was completed on 763 cases and 774 controls. Serum levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were measured in a subset of 394 cases and 397 controls.
Serum levels of 25(OH)D were inversely associated with advanced adenoma risk in women but not in men. Comparing those in the highest quintile with those in the lowest quintile, the risk for advanced adenoma decreased by 73% in women [odds ratio (OR) = 0.27, 95% confidence interval (95% CI) = 0.11-0.69; P for trend = 0.0002], while the risk did not decrease in men (OR = 1.10, 95% CI = 0.60-2.05; P for trend = 0.85). In women, 25(OH)D levels were significantly higher in current users of hormone replacement therapy (HRT) than in former or never HRT users. Neither serum 1,25(OH)(2)D nor VDR TaqI genotype was associated with advanced adenoma risk.
Higher serum 25(OH)D levels were associated with decreased adenoma risk. Serum 1,25(OH)(2)D and VDR TaqI genotype were not associated with adenoma risk.

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    • "Our meta-analysis of colorectal adenoma also showed no association with FokI or BsmI polymorphisms. Previous studies have reported inconsistent findings for other VDR polymorphisms in relation to colorectal adenoma or cancer [14,23,24,42-45]. "
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    ABSTRACT: Growing evidence suggests an elevated risk for colorectal neoplasia among individuals with low levels of vitamin D, the biological actions of which are mediated by the vitamin D receptor (VDR). To investigate the association among vitamin D status, VDR polymorphisms (FokI, and BsmI), and colorectal adenoma, we conducted a meta-analysis of nine studies of circulating levels of 25-hydroxyvitamin D (25(OH)D) and five studies of FokI or BsmI polymorphisms in relation to colorectal adenomas. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model. A total of 3398 colorectal adenomas for 25(OH)D and 1754 colorectal adenomas for VDR were included in the meta-analysis. We identified a significant inverse association between colorectal adenoma (combined RR, 0.93; 95% CI, 0.87-0.98 per 10 ng/mL increase in 25(OH)D levels). When we examined FokI and BsmI polymorphisms in the meta-analysis, we found no association for either FokI (combined RR, 1.00; 95% CI, 0.95-1.06) or BsmI (combined RR, 0.99; 95% CI, 0.93-1.05) in the additive model. These data suggest an inverse association between circulating 25(OH)D levels and colorectal adenoma risk.
    Nutrition research and practice 10/2011; 5(5):464-70. DOI:10.4162/nrp.2011.5.5.464 · 1.44 Impact Factor
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    • "Because only 43–63% of CRA are found in the distal colon and rectum (Fedirko et al., 2010; Haug et al., 2010; Takahashi et al., 2010), use of sigmoidoscopy may result in a certain misclassification regarding the presence or absence of adenomas. Studies using colonoscopy might be prone to find a stronger association between 25(OH)D and incident, sporadic CRA (Fedirko et al., 2010; Miller et al., 2007; Peters et al., 2004; Takahashi et al., 2010). Therefore, it is possible that studies based on sigmoidoscopy underestimate effects of serum vitamin D on incident, sporadic CRA. "
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    ABSTRACT: To perform a systematic review and meta-analysis of human studies on the association between serum 25 hydroxyvitamin D (25(OH)D) and incident, sporadic colorectal adenoma (CRA) and CRA recurrence. Relevant studies among humans were identified by systematically searching Ovid Medline, EMBASE, and ISI Web of Knowledge databases and by cross-referencing. Due to the heterogeneity across studies in categorizing serum vitamin D levels, all results were recalculated for an increase of serum 25(OH)D by 20 ng/ml. Summary odds ratios (ORs) were calculated using meta-analysis methods. Overall, 10 original studies were included. Specific results for incident CRA according to serum 25(OH)D were reported in 8 studies, and for CRA recurrence in 2 studies, respectively. In meta-analyses, summary ORs (95% confidence intervals) regarding incident and recurrent CRA, and both outcomes combined were 0.82 (0.69-0.97), 0.87 (0.56-1.35), and 0.84 (0.72-0.97), respectively, for an increase of 25(OH)D by 20 ng/ml. No publication bias was found. Our results support suggestions that serum 25(OH)D levels are inversely associated with CRA risk.
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    • "Details of these studies of colorectal adenoma, non-Hodgkins lymphoma (NHL) and prostate, breast, and pancreatic cancer are described elsewhere [8] [9] [10] [11] [12]. Briefly, we included 399 controls used for a study of colorectal adenoma (matched to cases by gender and race) [10], 286 controls used for a study of non-Hodgkin lymphoma [11], 713 controls used for a study of prostate cancer (matched to cases by age, time since screening, and year of follow-up) [8], 932 controls used for a study of breast cancer (matched to cases by age and year of blood draw) [9], and 350 used for a study of pancreatic cancer (matched to cases by age, gender, race and date of blood draw) [12]. Of these controls, 59 were included in more than one study; thus, in total 2621 control subjects from PLCO were included in this present data analysis. "
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    ABSTRACT: The aim of this study was to investigate modifiable predictors of vitamin D status in healthy individuals, aged 55-74, and living across the USA. Vitamin D status [serum 25-hydroxyvitamin D (25(OH)D)] was measured along with age and season at blood collection, demographics, anthropometry, physical activity (PA), diet, and other lifestyle factors in 1357 male and 1264 female controls selected from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort. Multivariate linear and logistic regression analyses were used to identify associations with vitamin D status. Three%, 29% and 79% of the population had serum 25(OH)D levels<25, <50 and <80 nmol/L, respectively. The major modifiable predictors of low vitamin D status were low vitamin D dietary and supplement intake, body mass index (BMI) >30 kg/m2, physical inactivity (PA) and low milk and calcium supplement intake. In men, 25(OH)D was determined more by milk intake on cereal and in women, by vitamin D and calcium supplement and menopausal hormone therapy (MHT) use. Thus targeting an increase in vigorous activity and vitamin D and calcium intake and decreasing obesity could be public health interventions independent of sun exposure to improve vitamin D status in middle-aged Americans.
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