Serum 25-Hydroxy Vitamin D and Prostate Cancer Risk in a Large Nested Case–Control Study (original) (raw)
Related papers
Purpose Circulating 25-hydroxyvitamin D (25(OH)D) may protect against prostate and other cancers. Few epidemiology studies have measured 25(OH)D on all participants , weakening the evidence-base through reduced statistical power and the potential for bias. We developed a score to predict individual 25(OH)D based on potential predictors, including sun exposure, nutrient intake, and vitamin D pathway genes, providing a method of substituting missing values. We assessed the usefulness of predicted 25(OH)D by comparison with multiple imputation of 25(OH)D levels. Methods Amongst 1,091 controls from a population-based case–control study (ProtecT), we quantified relationships of sun exposure, demographic, clinical, anthropologic, nutrient, and genetic data with circulating 25(OH)D and constructed several prediction scores from subsets of these measures. We investigated associations of three prostate cancer risk factors (PSA level, BMI, family history of prostate cancer) with 25(OH)D levels in sensitivity analyses based upon participants with measured 25(OH)D only and based upon the addition of all participants with missing 25(OH)D levels substituted by prediction score values or by multiple imputation. Results Our score accounted for 27.7% of the variation in measured 25(OH)D. Associations with risk factors of prostate cancer were consistent across the different estimates of 25(OH)D. However, standard deviations for the prediction score did not incorporate extra error from prediction. Multiple imputation of missing 25(OH)D values predicted a more realistic range of 25(OH)D. Conclusion In epidemiological studies of cancer risk associated with vitamin D, multiple imputation of missing 25(OH)D is preferable to prediction scores, as a wider range of 25(OH)D levels are imputed and appropriate confidence intervals calculated.
Serum Vitamin D Concentration and Prostate Cancer Risk: A Nested Case-Control Study
JNCI Journal of the National Cancer Institute, 2008
Vitamin D is a prohormone that can be supplied from dietary sources and generated endogenously from sunlight exposure ( 1 ). The primary circulating form of vitamin D is 25-hydroxyvitamin D [25(OH)D]. Prostate and renal cells can convert 25(OH)D to 1,25dihydroxyvitamin D [1,25(OH) 2 D], which influences the expression of many proteins that are involved in cellular differentiation, proliferation, and apoptosis ( 2 ). Although 1,25(OH) 2 D is the biologically active form of vitamin D, serum 25(OH)D is considered to be the better biomarker of vitamin D status because it reflects endogenous and exogenous vitamin D sources ( 1 ).
Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland)
Cancer causes & control : CCC, 2000
The aim was to evaluate the association between serum vitamin D (25-hydroxyvitamin D) level and risk of prostate cancer. The nested case-control study was based on a 13-year follow-up of about 19,000 middle-aged men who attended the first screening visit within the Helsinki Heart Study and were free of clinically verified prostate cancer at baseline. Through record linkage with the files of the Finnish Cancer Registry, 149 prostate cancer cases were identified in the cohort. They were matched (1:4) to probability density sampled controls for age, time of sample retrieval, and residence. Serum levels of 25-hydroxyvitamin D (25-VD) at entry were measured for cases and controls. The relative risks of prostate cancer were derived using conditional logistic regression analysis. Prostate cancer risk, analyzed by quartiles of the 25-VD levels, was inversely related to 25-VD. Men with 25-VD concentration below the median had an adjusted relative risk (OR) of 1.7 compared to men with 25-VD l...
2012
Epidemiological studies suggest that vitamin D protects against prostate cancer, although evidence is limited and inconsistent. We investigated associations of circulating total 25-hydroxyvitamin D (25(OH)D) with prostate specific antigen-detected prostate cancer in a case-control study nested within the prostate testing for cancer and treatment (ProtecT) trial. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) quantifying the association between circulating total 25(OH)D and prostate cancer. In case-only analyses, we used unconditional logistic regression to quantify associations of total 25(OH)D with stage (advanced vs. localized) and Gleason grade (high-grade (!7) vs. low-grade (<7)). Predetermined categories of total 25(OH)D were defined as: high: !30 ng/mL; adequate: 20 -<30 ng/mL; insufficient: 12 -<20 ng/mL; deficient: <12 ng/mL. Fractional polynomials were used to investigate the existence of any U-shaped relationship. We included 1,447 prostate cancer cases (153 advanced, 469 high-grade) and 1,449 healthy controls. There was evidence that men deficient in vitamin D had a 2-fold increased risk of advanced versus localized cancer (OR for deficient vs. adequate total 25(OH)D 5 2.33, 95% CI: 1.26, 4.28) and high-grade versus low-grade cancer (OR for deficient vs. adequate total 25(OH)D 5 1.78, 95% CI: 1.15, 2.77). There was no evidence of a linear association between total 25(OH)D and prostate cancer (p 5 0.44) or of an increased risk of prostate cancer with high and low vitamin D levels. Our study provides evidence that lower 25(OH)D concentrations were associated with more aggressive cancers (advanced versus localized cancers and high-versus low-Gleason grade), but there was no evidence of an association with overall prostate cancer risk.
2009
Results from the majority of studies show little association between circulating concentrations of vitamin D and prostate cancer risk, a finding that has not been demonstrated in a wider European population, however. The authors examined whether vitamin D concentrations were associated with prostate cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (1994-2000). Serum concentrations of 25-hydroxyvitamin D were measured in 652 prostate cancer cases matched to 752 controls from 7 European countries after a median follow-up time of 4.1 years. Conditional logistic regression models were used to calculate odds ratios for prostate cancer risk in relation to serum 25-hydroxyvitamin D after standardizing for month of blood collection and adjusting for covariates. No significant association was found between 25-hydroxyvitamin D and risk of prostate cancer (highest vs. lowest quintile: odds ratio ¼ 1.28, 95% confidence interval: 0.88, 1.88; P for trend ¼ 0.188). Subgroup analyses showed no significant heterogeneity by cancer stage or grade, age at diagnosis, body mass index, time from blood collection to diagnosis, or calcium intake. In summary, the results of this large nested case-control study provide no evidence in support of a protective effect of circulating concentrations of vitamin D on the risk of prostate cancer. prostatic neoplasms; serum; vitamin D; 25-hydroxyvitamin D 2
Plasma levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and the risk of prostate cancer
The Journal of Steroid Biochemistry and Molecular Biology, 2004
In the US, prostate cancer (PCa) has the highest incidence rate of all cancers in males, with few known modifiable risk factors. Some studies support an association between the Vitamin D metabolites, 1,25-dihydroxyvitamin D (1␣,25(OH) 2 D 3) and/or 25-hydroxyvitamin D (25(OH)D 3), and prostate cancer, while others have yielded conflicting results. 1␣,25(OH) 2 D 3 has anti-proliferative and pro-differentiating effects in prostate cancer cell lines, and levels of circulating 25(OH)D 3 may be important as PCa cells possess 1-␣-hydroxylase activity. Using a nested case-control design, we evaluated whether plasma levels of 25(OH)D 3 and 1␣,25(OH) 2 D 3 were associated with prostate cancer risk in participants from the Nutritional Prevention of Cancer (NPC) trial. With 83 cases and 166 matched controls, we calculated the adjusted odds ratios for increasing plasma levels of 25(OH)D 3 and 1␣,25(OH) 2 D 3. Compared to the lowest tertile of plasma 25(OH)D 3 levels, the adjusted odds ratios were 1.71 (0.68-4.34) and 0.75 (0.29-1.91); the corresponding odds ratios for 1␣,25(OH) 2 D 3 were 1.44 (0.59-3.52) and 1.06 (0.42-2.66). Given the pivotal effects of the Vitamin D receptor on gene transcription, it is likely that the anti-carcinogenic effects of Vitamin D that have previously been described are related to the activity and expression of the Vitamin D receptor and should be investigated further.
CONTEXT AND OBJECTIVE: Prostate, colorectal and lung cancers are common in men. In this study, we aimed to determine whether vitamin D status is associated with the incidence of these cancers in older men. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: 4208 older men aged 70-88 years in Perth, Western Australia. MAIN OUTCOME MEASURES: Plasma 25-hydroxyvitamin D [25(OH)D] concentration was measured by immunoassay. New diagnoses of prostate, colorectal and lung cancers were determined via electronic record linkage. RESULTS: During a mean follow-up of 6.7±1.8 years, there were 315, 117 and 101 new diagnoses of prostate, colorectal and lung cancer. In multivariate competing risks proportional hazards models, every 10 nmol/l decrease in 25(OH)D concentration was associated with a 4% reduction in prostate cancer incidence (sub-hazard ratio [SHR] 0.96, 95% confidence interval [CI] 0.92-1.00). Every halving of 25(OH)D concentration was associated with a 21% reduction in incident prostate cancer in multivariate analysis (SHR 0.79, 95% CI 0.63-0.99). Following exclusion of prostate cancer cases diagnosed within 3 years of blood sampling, low 25(OH)D <50 nmol/l was associated with lower incident prostate cancer, and higher 25(OH)D >75 nmol/l was associated with higher incidence, when compared to the reference range 50-75 nmol/l, respectively (p = 0.027). Significant associations were also observed when 25(OH)D was modeled as a quantitative variable. No associations were observed between plasma 25(OH)D concentration with incidence of colorectal or lung cancer. CONCLUSION: Lower levels of vitamin D may reduce prostate cancer risk in older men. By contrast, levels of vitamin D did not predict incidence of colorectal or lung cancers. Further studies are needed to determine whether a causal relationship exists between vitamin D and prostate cancer in ageing men.
Plasma 25-hydroxyvitamin D and prostate cancer risk: The Multiethnic Cohort
European Journal of Cancer, 2010
The purpose of this study was to examine the relationship of plasma 25-hydroxyvitamin D (25(OH) D) concentrations to prostate cancer within a large multiethnic cohort in Hawaii and California using a nested case-control design. The study included 329 incident prostate cancer cases of African American, Native Hawaiian, Japanese, Latino, and White ancestry, and 656 controls matched on age, race/ethnicity, date/time of blood collection, and fasting status. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). No association with prostate cancer risk was found in an analysis based on quartiles of 25(OH)D. When clinically defined cutpoints were used, there was no increased risk for the lowest 25(OH)D concentration (OR for <20 vs. 30-<50 ng/ml = 1.10, 95% CI = 0.68-1.78), while there was a suggestive increased risk for higher concentrations (OR for ≥50 ng/ml = 1.52, 95% CI = 0.92-2.51). The findings from this prospective study of men in the Multiethnic Cohort do not support the hypothesis that vitamin D lowers the risk of prostate cancer. Further follow-up is warranted to determine whether the findings are consistent across ethnic groups.
Vitamin D and prostate cancer risk: a review of the epidemiological literature
Prostate Cancer and Prostatic Diseases, 2009
Prostate cancer is the most commonly diagnosed cancer in the United States. Prostate cells contain vitamin D receptors as well as enzymes necessary for vitamin D metabolism. Vitamin D metabolites have an antiproliferative and a pro-differentiating effect on prostate cancer cell lines in vitro and in vivo. As a result, there has been an emerging interest in the potential role of vitamin D in the etiology of prostate cancer. This review summarizes all available epidemiological literature on the association between dietary vitamin D, circulating levels of vitamin D and sunlight exposure in relation to prostate cancer risk. To place these studies in context, we also provide some background information on vitamin D, such as its dietary sources, metabolism, optimal levels, hypovitaminosis and relationship with the prostate.
Circulating 25-hydroxyvitamin D, vitamin D-binding protein and risk of prostate cancer
International Journal of Cancer, 2012
We recently reported a significant positive association between 25-hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, and prostate cancer risk. To further elucidate this association, we examined the influence of vitamin D binding protein (DBP), the primary transporter of vitamin D compounds in the circulation. Prediagnostic serum concentrations of DBP were assayed for 950 cases and 964 matched controls with existing 25(OH)D measurements within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI), and statistical tests were two-sided. Serum DBP modified the association between serum 25(OH)D and prostate cancer, with higher risk for elevated 25(OH)D levels observed primarily among men having DBP concentrations above the median (OR=1.81, 95% CI 1.18-2.79 for highest vs. lowest quintile, ptrend = 0.001) compared to those with DBP below the median (OR=1.22, 95% CI 0.81-1.84, ptrend 0.97; p-interaction = 0.04). Serum DBP was not associated with prostate cancer risk overall (OR=0.96, 95% CI 0.70-1.33 for highest vs. lowest quintile); however, high serum DBP was associated with significantly decreased risk of prostate cancer in men with lower (<median) 25(OH)D concentrations (OR=0.59, 95% CI 0.38-0.90 for highest vs. lowest quintile, p-trend = 0.003) and increased risk in men with higher 25(OH)D concentrations (OR = 1.47, 95% CI 0.98-2.20, p-trend 0.10, p-interaction = 0.02). Our data suggest that the primary vitamin D carrier protein, DBP, modulates the impact of vitamin D status on prostate cancer.