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All, I'm not sure if many people around here still do dairy, especially high fat dairy. But if you do, you might want to think again, and not just for the sake of the animals, but for the sake of your heart. This new study  analyzed the data from over 200K people in the Health Care Professionals and Nurses Health Studies followed for 20-30 years. The good news? Dairy fat intake was associated with a slightly lower cardiovascular disease risk than other forms of animal fat. The bad news? Replacing 5% of energy from PUFA for 5% more dairy fat resulted in a 24% increase in your risk of cardiovascular disease. Replacing dairy with whole grains was even better (28% lower risk of CVD). Here is a graph showing the estimated impact of substituting various other foods in place of dairy fat on risk of cardiovascular disease overall (A), as well as broken down by coronary heart disease (B) vs. stroke (C ): The authors summarize as follows: To our knowledge, this is the first large-scale prospective study to examine dairy fat intake and its replacement with other types of fat in relation to CVD risk... These results support current recommendations to replace animal fats, including dairy fat, with vegetable sources of fats and polyunsaturated fat (both n–6 and n–3) in the prevention of CVD. Sorry to be the bearer of bad news, cheese lovers. Whom I kidding, no I'm not... --Dean ------------  Am J Clin Nutr. 2016 Aug 24. pii: ajcn134460. [Epub ahead of print] Dairy fat and risk of cardiovascular disease in 3 cohorts of US adults. Chen M(1), Li Y(2), Sun Q(3), Pan A(4), Manson JE(5), Rexrode KM(5), Willett WC(6), Rimm EB(6), Hu FB(7). Full text: http://sci-hub.cc/10.3945/ajcn.116.134460 BACKGROUND: Few prospective studies have examined dairy fat in relation to cardiovascular disease (CVD). OBJECTIVE: We aimed to evaluate the association between dairy fat and incident CVD in US adults. DESIGN: We followed 43,652 men in the Health Professionals Follow-Up Study (1986-2010), 87,907 women in the Nurses' Health Study (1980-2012), and 90,675 women in the Nurses' Health Study II (1991-2011). Dairy fat and other fat intakes were assessed every 4 y with the use of validated food-frequency questionnaires. RESULTS: During 5,158,337 person-years of follow-up, we documented 14,815 incident CVD cases including 8974 coronary heart disease cases (nonfatal myocardial infarction or fatal coronary disease) and 5841 stroke cases. In multivariate analyses, compared with an equivalent amount of energy from carbohydrates (excluding fruit and vegetables), dairy fat intake was not significantly related to risk of total CVD (for a 5% increase in energy from dairy fat, the RR was 1.02; 95% CI: 0.98, 1.05), coronary heart disease (RR: 1.03; 95% CI: 0.98, 1.09), or stroke (RR: 0.99; 95% CI: 0.93, 1.05) (P > 0.05 for all). In models in which we estimated the effects of exchanging different fat sources, the replacement of 5% of energy intake from dairy fat with equivalent energy intake from polyunsaturated fatty acid (PUFA) or vegetable fat was associated with 24% (RR: 0.76; 95% CI: 0.71, 0.81) and 10% (RR: 0.90; 95% CI: 0.87, 0.93) lower risk of CVD, respectively, whereas the 5% energy intake substitution of other animal fat with dairy fat was associated with 6% increased CVD risk (RR: 1.06; 95% CI: 1.02, 1.09). CONCLUSIONS: The replacement of animal fats, including dairy fat, with vegetable sources of fats and PUFAs may reduce risk of CVD. Whether the food matrix may modify the effect of dairy fat on health outcomes warrants further investigation. © 2016 American Society for Nutrition. DOI: 10.3945/ajcn.116.134460 PMID: 27557656
All, On the CR email list Al recently posted a series of studies, included below [1-3], showing that higher levels of serum vitamin D were associated with increased risk of prostate cancer. But the most recent such study Al posted , found the opposite - increased vitamin D level was associated with a decreased risk of prostate cancer. What the authors of  suggest in the discussion (included below) is that there may be a U-shaped curve between serum vitamin D and prostate cancer risk, with the 'sweet spot' being in the neighborhood of 20-30 ng/ml (or equiv. 50-75 nmol/l) range. The bottom line suggested by  appears to be that we want to have sufficient Vitamin D, but not too much, in order to avoid prostate cancer. Of course, men get a lot of their vitamin D from D-fortified dairy products, which may be driving some of this apparent positive association between vitamin D level and prostate cancer, since this recent meta-analysis  found: High intakes of dairy products, milk, low-fat milk, cheese, and total, dietary, and dairy calcium, but not supplemental or nondairy calcium, may increase total prostate cancer risk. So it is possible that higher levels of vitamin D are a marker for higher intake of dairy products in the general population, which may be driving the development of prostate cancer. --Dean --------------  Plasma 25-hydroxyvitamin D and prostate cancer risk: the multiethnic cohort. Park SY, Cooney RV, Wilkens LR, Murphy SP, Henderson BE, Kolonel LN. Eur J Cancer. 2010 Mar;46(5):932-6. doi: 10.1016/j.ejca.2009.12.030. Epub 2010 Feb 8. PMID: 20064705 Free PMC Article http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834847/ file:///C:/Documents%20and%20Settings/user/My%20Documents/Downloads/nihms169878%20(1).pdf Abstract 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. Keywords: 25-hydroxyvitamin D, multiethnic cohort, nested case-control study, plasma, prostate neoplasms ---------  Circulating levels of 25-hydroxyvitamin D and prostate cancer prognosis. Holt SK, Kolb S, Fu R, Horst R, Feng Z, Stanford JL. Cancer Epidemiol. 2013 Oct;37(5):666-70. doi: 10.1016/j.canep.2013.07.005. Epub 2013 Aug 20. PMID: 23972671 PMC Article http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864767/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864767/pdf/nihms517958.pdf Abstract OBJECTIVES: Ecological, in vitro, and in vivo studies demonstrate a link between vitamin D and prostate tumor growth and aggressiveness. The goal of this study was to investigate whether plasma concentration of vitamin D is associated with survivorship and disease progression in men diagnosed with prostate cancer. MATERIALS AND METHODS: We conducted a population-based cohort study of 1476 prostate cancer patients to assess disease recurrence/progression and prostate cancer-specific mortality (PCSM) risks associated with serum levels of 25(OH) vitamin D [25(OH)D]. RESULTS: There were 325 recurrence/progression and 95 PCSM events during an average of 10.8 years of follow-up. Serum levels of 25(OH)D were not associated with risk of recurrence/progression or mortality. Clinically deficient vitamin D levels were associated with an increased risk of death from other causes. CONCLUSIONS: We did not find evidence that serum vitamin D levels measured after diagnosis affect prostate cancer prognosis. Lower levels of vitamin D were associated with risk of non-prostate cancer mortality. KEYWORDS: 1,25(OH)(2)D; 1,25-dihydroxyvitamin D(3); 25(OH) vitamin D; 25(OH)D; ADT; BMI; Cohort studies; Epidemiologic studies; FFQ; HR; Humans; Male; Mortality; PCSM; PCa; PH; PSA; Prognosis; Prostatic neoplasms; Vitamin D/blood*; androgen deprivation therapy; body mass index; food frequency questionnaire; hazard ratio; proportional hazards; prostate cancer; prostate cancer-specific mortality; prostate specific antigen ----------  In older men, lower plasma 25-hydroxyvitamin D is associated with reduced incidence of prostate, but not colorectal or lung cancer. Wong YY, Hyde Z, McCaul KA, Yeap BB, Golledge J, Hankey GJ, Flicker L. PLoS One. 2014 Jun 20;9(6):e99954. doi: 10.1371/journal.pone.0099954. eCollection 2014. Erratum in: PLoS One. 2014;9(9):e109511. PMID: 24949795 Free PMC Article http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065010/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065010/pdf/pone.0099954.pdf Abstract 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. ----------  A prospective study of plasma 25-hydroxyvitamin D concentration and prostate cancer risk. Deschasaux M, Souberbielle JC, Latino-Martel P, Sutton A, Charnaux N, Druesne-Pecollo N, Galan P, Hercberg S, Le Clerc S, Kesse-Guyot E, Ezzedine K, Touvier M. Br J Nutr. 2016 Jan;115(2):305-14. doi: 10.1017/S0007114515004353. Epub 2015 Nov 16. PMID: 26568368 Abstract Mechanistic hypotheses suggest that vitamin D and the closely related parathyroid hormone (PTH) may be involved in prostate carcinogenesis. However, epidemiological evidence is lacking for PTH and inconsistent for vitamin D. Our objectives were to prospectively investigate the association between vitamin D status, vitamin D-related gene polymorphisms, PTH and prostate cancer risk. A total of 129 cases diagnosed within the Supplémentation en Vitamines et Minéraux Antioxydants cohort were included in a nested case-control study and matched to 167 controls (13 years of follow-up). 25-Hydroxyvitamin D (25(OH)D) and PTH concentrations were assessed from baseline plasma samples. Conditional logistic regression models were computed. Higher 25(OH)D concentration was associated with decreased risk of prostate cancer (ORQ4 v. Q1 0·30; 95 % CI 0·12, 0·77; P trend=0·007). PTH concentration was not associated with prostate cancer risk (P trend=0·4) neither did the studied vitamin D-related gene polymorphisms. In this prospective study, prostate cancer risk was inversely associated with 25(OH)D concentration but not with PTH concentration. These results bring a new contribution to the understanding of the relationship between vitamin D and prostate cancer, which deserves further investigation. KEYWORDS: 1; 25(OH)2D 1; 25(OH)D 25-hydroxyvitamin D; 25-Hydroxyvitamin D; 25-dihydroxyvitamin D; 25-dihydroxyvitamin D3 24-hydroxylase; CYP24A1 1; CaSR Ca-sensing receptor; GC vitamin D-binding globulin; MAF minor allele frequency; Nested case–control studies; PTH parathyroid hormone; Parathyroid hormone; Prostate cancer risk; RXR retinoid X receptor; SNP; SU.VI.MAX Supplémentation en Vitamines et Minéraux Antioxydants; VDR vitamin D receptor; gc-globulin or group-specific component Vitamin D is a prohormone synthesised in the skin from UVB exposure and absorbed from scarce dietary sources. It is first converted to 25-hydroxyvitamin D (25(OH)D) – its main circulating form – and then to 1,25-dihydroxyvitamin D (1,25(OH)2D) – its biologically active form. As 25(OH)D-to-1,25(OH)2D conversion and 1,25(OH)2D signalling can take place directly in prostate tissues(1), vitamin D is thought to play a role in the prevention of prostate cancer through pro-differentiation, pro-apoptosis, anti-proliferative and growth control activities, as suggested by experimental studies(2–4). However, so far, epidemiological evidence regarding the relationship between 25(OH)D concentration and prostate cancer risk has been inconsistent. On the basis of a dose–response meta-analysis that involved fifteen prospective studies, the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR)(5), as part of the Continuous Update Project 2014 on prostate cancer, stated that the level of proof for the association between 25(OH)D concentration and prostate cancer risk was still ‘limited-no conclusion’. Most of the studies included in this meta-analysis observed null results. Besides, vitamin D is primarily involved in Ca homoeostasis: 1,25(OH)2D increases Ca concentration through enhanced intestinal Ca absorption, reabsorption of Ca from kidneys and bone resorption. Renal 25(OH)D-to-1,25(OH)2D conversion is induced by parathyroid hormone (PTH) secretion in response to low Ca concentration. 1,25(OH)2D exerts in turn a negative feedback on PTH secretion(6–8). Vitamin D and PTH are thus closely related. To our knowledge, only one prospective study has investigated the association between PTH concentration and prostate cancer risk, with null result(9). Several genes involved in vitamin D metabolism, in particular signalling (vitamin D receptor (VDR) and retinoid X receptor (RXR)), transportation (vitamin D-binding protein, also known as gc-globulin or group-specific component (GC)) and degradation (1,25-dihydroxyvitamin D3 24-hydroxylase (CYP24A1)), or in Ca homoeostasis (Ca-sensing receptor (CaSR)) could also play a role in prostate cancer aetiology(2). Recent meta-analyses found null associations between VDR BsmI, FokI and Cdx2 polymorphisms and prostate cancer risk(10–12). The epidemiological literature dealing with polymorphisms of other genes (GC, CYP24A1, RXR and CaSR) in relation to prostate cancer risk is scarce(13–16). Thus, our objective was to prospectively investigate the associations between prostate cancer risk and vitamin D status (25(OH)D concentration), plasma PTH concentration and polymorphisms of genes involved in vitamin D metabolism. Methods Subjects The Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) study was initially designed as a double-blind placebo-controlled trial (Trial Registration clinicaltrials.gov Identifier: NCT00272428) with purpose to assess the influence of a daily supplementation with nutritional doses of antioxidants (single capsule of a combination of ascorbic acid (120 mg), vitamin E (30 mg), ß-carotene (6 mg), Se (100 µg) and Zn (20 mg) or placebo) on the incidence of CVD and cancers(17). A total of 13 017 participants were enrolled in 1994–1995 for an 8-year-intervention trial and followed up for health events until September 2007. Participants were advised against taking any self-prescribed supplements (vitamin D and others) during the trial. ... Results A total of 129 prostate cancer cases diagnosed within the SU.VI.MAX cohort were included in this study. Mean age at diagnosis was 63·0 years and mean baseline-to-diagnosis time was 8·3 years. Of the cases, 49·2 % had a Gleason’s score =/>7. A total of 167 controls were randomly selected and matched to the cases. Table 1 summarises the characteristics of prostate cancer cases and controls. Compared with controls, prostate cancer cases were more likely to have a lower vitamin D status at baseline and to be better educated. Severe vitamin D deficiency (<10 ng/ml) was observed for 14·0 % of cases and 13·8 % of controls, and vitamin D insufficiency (<20 ng/ml) was observed for 62·8 % of cases and 54·5 % of controls, with no statistically significant difference between cases and controls. A seasonal fluctuation of vitamin D status was observed in controls with decreasing vitamin D status from October to March (shortening days) and increasing vitamin D status in April–May (extending days). All studied SNP respected the Hardy–Weinberg’s equilibrium (P>0·05). The repartition of subjects across the different genotypes was in accordance with that observed in European reference populations (CSHL-HapMap-CEU and 1000GENOMES-phase_1_EUR) for all SNP (P>0·05). 25(OH)D concentration was inversely associated with prostate cancer risk (ORper 1 ng/ml 0·96; 95 % CI 0·93, 1·00; Ptrend=0·04; ORQ4 v. Q1 0·30; 95 % CI 0·12, 0·77; Ptrend=0·007; OR<20 v. =/>20 ng/ml 0·44; 95 % CI 0·23, 0·85; P=0·01, Table 2; ORper 30 nmol/l 0·64; 95 % CI 0·42, 0·97; Ptrend=0·04, data not tabulated). Using the quartile coding this inverse association was observed in particular for cases with a Gleason’s score <7 (sixty-nine cases/ninety controls, ORQ4 v. Q1 0·03; 95 % CI 0·003, 0·40; Ptrend=0·02; data not tabulated), whereas it was not significant for cases with a Gleason’s score =/>7 (sixty cases/seventy-seven controls, ORQ4 v. Q1 0·96; 95 % CI 0·23, 4·05; Ptrend=0·5; data not tabulated). However, using the continuous 25(OH)D variable or the 20 ng/ml cut-off, these associations were not significant in both Gleason’s subgroups. Exclusion of cases diagnosed during the first 5 years of follow-up provided similar results (109 cases/140 controls, ORper 1 ng/ml 0·96; 95 % CI 0·93, 1·00; Ptrend=0·04; ORQ4 v. Q1 0·33; 95 % CI 0·12, 0·86; Ptrend=0·01; OR<20 v. =/>20 ng/ml 0·45; 95 % CI 0·23, 0·89; P=0·02; data not tabulated). No interaction was observed between 25(OH)D concentration and the intervention group of the SU.VI.MAX trial (Pinteraction>0·1 for all codings). Associations between 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) plasma concentrations, and prostate cancer risk, from conditional logistic regression, Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort, France (1994–2007) (Odds ratios and 95 % confidence intervals) Table 2 Associations between 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) plasma concentrations, and prostate cancer risk, from conditional logistic regression, Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort, France (1994–2007) (Odds ratios and 95 % confidence intervals) % confidence intervals) -------------------------------------------------- - === - ===Quartiles*===Insufficiency - === Per 1 unit increment===Q1 Q2 Q3 Q4 <20 ng/ml =/>20 ng/ml - === OR 95 % CI Ptrend===OR OR 95 % CI OR 95 % CI OR 95 % CI Ptrend OR OR 95 % CI P -------------------------------------------------- 25(OH)D (ng/ml) Cases/controls 129/167 42/32 31/43 25/49 31/43 81/91 48/76 Model 1† 0·96 0·93, 1·00 0·04 1·00 0·44 0·19, 1·04 0·18 0·07, 0·49 0·30 0·12, 0·77 0·007 1·00 0·44 0·23, 0·85 0·01 Cases/controls 96/123 27/20 23/35 20/35 26/33 57/66 39/57 Model 2† 0·95 0·91, 1·00 0·06 1·00 0·35 0·12, 1·07 0·13 0·04, 0·49 0·25 0·08, 0·81 0·02 1·00 0·43 0·19, 1·00 0·05 Cases/controls 96/123 27/20 23/35 20/35 26/33 57/66 39/57 Model 3† 0·96 0·91, 1·01 0·08 1·00 0·33 0·11, 1·03 0·12 0·03, 0·46 0·28 0·08, 0·95 0·03 1·00 0·43 0·18, 1·01 0·05 -------------------------------------------------- PTH (pg/ml) Cases/controls 129/167 31/43 34/40 34/40 30/44 Model 1† 0·97 0·94, 1·01 0·1 1·00 0·90 0·40, 2·05 0·95 0·40, 2·27 0·66 0·28, 1·55 0·4 Cases/controls 96/123 20/35 30/26 27/30 19/32 Model 2† 0·96 0·91, 1·01 0·09 1·00 1·72 0·60, 4·90 1·95 0·62, 6·18 0·77 0·25, 2·36 0·6 Cases/controls 96/123 20/35 30/26 27/30 19/32 Model 3† 0·96 0·91, 1·01 0·1 1·00 1·63 0·56, 4·77 2·25 0·67, 7·59 0·81 0·25, 2·62 0·8 -------------------------------------------------- Q, quartiles. * Model 1: cut-offs for quartiles of 25(OH)D plasma concentration (ng/ml) and PTH plasma concentration (pg/ml) were, respectively, 12·9/18·2/24·7 and 20·9/26·0/30·6. Models 2 and 3 are restricted to men who provided at least three valid 24 h-dietary records (ninety-six cases/123 controls): cut-offs for quartiles of 25(OH)D plasma concentration (ng/ml) and PTH plasma concentration (pg/ml) were, respectively, 13·7/18·5/25·2 and 20·9/25·9/30·2. † Model 1 was adjusted for age at baseline (continuous, matching factor), intervention group of the initial SU.VI.MAX trial (antioxidants/placebo, matching factor), month of blood draw (October–November/December–January/February–March/April–May), educational level (primary/secondary/superior), physical activity (irregular/<1 h/d walking equivalent/=/>1 h/d walking equivalent), alcohol intake (g/d, continuous), smoking status (never/former/current), height (cm, continuous), BMI (kg/m², continuous, matching factor), family history of prostate cancer (yes/no) and baseline serum prostate-specific antigen concentration (<3/=/>3 ng/l). Model 2 corresponds to model 1 further adjusted for energy intake (without alcohol) (continuous, kJ/d (kcal/d)), dietary intakes of Ca intake (continuous, mg/d) and dairy products (continuous, g/d), plasma Se (continuous, µmol/l) and Alpha-tocopherol (continuous, µmol/l) concentrations. Model 3 corresponds to model 2 with further mutual adjustment for 25(OH)D and PTH plasma concentrations (continuous). Plasma PTH concentration was not associated with prostate cancer risk (ORQ4 v. Q1 0·66; 95 % CI 0·28, 1·55; Ptrend=0·4) (Table 2). This result was similar (124 cases/157 controls) after removing participants with possibly abnormal PTH values that may suggest potential hyperparathyroidism (i.e. PTH=/>50·8 pg/ml if 25(OH)D<20 ng/ml, PTH=/>45·5 pg/ml if 20 ng/ml</=25(OH)D<30 ng/ml and PTH=/>45·3 pg/ml if 25(OH)D=/>30 ng/ml, as previously recommended(22)). Dietary Ca intake was not associated with prostate cancer risk (ninety-six cases/123 controls, ORQ4 v. Q1 0·83; 95 % CI 0·20, 3·43; Ptrend=0·5, data not tabulated), nor did dietary intake of vitamin D (ninety-six cases/123 controls, ORQ4 v. Q1 1·05; 95 % CI 0·40, 2·81; Ptrend=0·7, data not tabulated). All results were similar when models were further adjusted for dietary variables (although some of the results were only borderline significant due to loss of statistical power: ninety-six cases/123 controls), dietary Ca and mutual adjustments for 25(OH)D and PTH. Two-way interactions between 25(OH)D, PTH and dietary Ca intake were not statistically significant (all P>0·1, data not shown). No association was observed between the ten studied vitamin D-related SNP and prostate cancer risk in the codominant (Table 3), dominant and recessive models (data not tabulated). No interaction was observed between the SNP and 25(OH)D concentration (all P>0·1, data not shown). As no association was detected between the ten SNP and prostate cancer with a P value threshold of 0·05, no association was detected after adjustment for multiple testing (Bonferroni correction) (data not shown). Associations between SNP of genes involved in vitamin D metabolism and prostate cancer risk, from conditional logistic regression, Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort, France (1994–2007) (Odds ratios and 95 % confidence intervals) Discussion In this prospective study, plasma 25(OH)D concentration was inversely associated with prostate cancer risk. No association was detected for plasma PTH concentration or the studied SNP. We observed an inverse association between 25(OH)D concentration and prostate cancer risk. Recently, a high v. low meta-analysis by Xu et al.(27) (summary ORhigh v. low 1·17; 95 % CI 1·05, 1·30) and a dose–response meta-analysis by the WCRF(5) (summary RRper 30 nmol/l 1·04; 95 % CI 1·00, 1·07) suggested an increased risk. However, in a previous study by Tuohimaa et al.(28), both high and low 25(OH)D concentrations were associated with increased prostate cancer risk: increased risk was observed for 25(OH)D concentration =/>32 or <15·6 ng/ml compared with 16–23·6 ng/ml. This U-shaped association is supported by the evidence of non-linearity observed in the WCRF dose–response meta-analysis(5). In our study, the range of 25(OH)D concentrations observed (95th percentile=36·3 ng/ml) may be positioned in the left part of this U-shaped curve, which may explain why a decreased prostate cancer risk was observed for 25(OH)D=/>20 ng/ml (insufficiency) or =/>18·2 ng/ml (median) compared with 25(OH)D<20 or <12·9 ng/ml (quartile 1 (Q1)), respectively. Consistently, a recent study by Kristal et al.(29) observed a decreased prostate cancer risk associated with 25(OH)D concentrations between 23·3 and 29·2 ng/ml (3rd quintile) compared with 25(OH)D<17·7 ng/ml (1st quintile). In contrast, some studies observing an increased risk may involve 25(OH)D concentrations situated in the right part of the U-shaped curve. For example, Brandstedt et al.(9) observed an increased risk for 25(OH)D concentrations=/>34 ng/ml compared with 25(OH)D concentrations</=27·2 ng/ml, and Meyer et al.(30) observed an increased risk for 25(OH)D concentrations=/>28 ng/ml compared with 25(OH)D concentrations between 20 and 28 ng/ml. Studies observing non-significant results may involve middle-range concentrations (such as the study by Skaaby et al.(31)). However, this point remains unclear as some studies that involved high 25(OH)D concentrations observed non-significant results(32,33), and some other studies observed a significant direct association between prostate cancer risk and 25(OH)D concentrations, even at relatively low levels(34). Thus, further studies are needed that take into account the distribution of 25(OH)D concentrations in the studied population and its position in the potential U-shaped curve. In addition, it has been suggested that large seasonal fluctuations of vitamin D status may also contribute to explain the positive association between 25(OH)D concentration and prostate cancer risk in some studies(35), adding to the complexity of this relationship. In the SU.VI.MAX cohort (Touvier et al.(21) and Table 1), seasonal fluctuation of vitamin D status was moderate with the lowest 25(OH)D concentrations observed in late winter/early spring (shorter days), consistently with the existing literature in France(36) and in other countries such as the USA(37–39). The potentially protective role of vitamin D in prostate carcinogenesis observed in our study is supported by mechanistic hypotheses. Indeed, prostate cells can express the 25(OH)D-to-1,25(OH)2D conversion enzyme and the vitamin D receptor(1) and vitamin D is thought to be involved in several cell regulation pathways: pro-differentiation, pro-apoptosis, anti-proliferation and cell growth(2–4). In our study, when 25(OH)D was coded into quartiles, a decreased prostate cancer risk was observed for Gleason’s score <7 but not for Gleason’s score =/>7. However, when using the other codings (continuous and 20 ng/ml cut-off), the association was non-significant in both cancer subgroups. As statistical power was limited in stratified analyses, these results should be considered with caution and further explored in large prospective studies. Thus far, the results regarding potential differences according to prostate cancer stage/grade are unclear, as shown in the WCRF meta-analysis(5), where no difference was observed between advanced/high-grade or non-advanced/low-grade prostate cancers (non-significant results in both groups), or in a recent study by Kristal et al.(29), where a decreased prostate cancer risk was observed whatever the Gleason’s score. The lack of association between the ten studied SNP and prostate cancer risk in our study does not seem to support the protective role of vitamin D in prostate carcinogenesis suggested by our results on plasma 25(OH)D concentration. However, in this study, statistical power was limited in the analyses of SNP, especially for the homozygote mutant genotypes. This could explain the null associations observed. Consistent with our findings, several meta-analyses(10–12) and one recent prospective study(13) found null associations between VDR BsmI, FokI and Cdx2 polymorphisms and prostate cancer risk. Another study (not included in these meta-analyses) observed an increased prostate cancer associated with VDR BsmI GG genotype among men in the first tertile of plasma 25(OH)D concentration. The epidemiological literature dealing with the other studied polymorphisms is scarce. One study(13) observed an increased prostate cancer risk associated with GC rs4588 T allele or GC rs7041 A allele. In SU.VI.MAX(21), these alleles were associated with a lower vitamin D status. Another study(15) observed a decreased lethal prostate cancer risk associated with CaSR rs1801725 among men with low plasma 25(OH)D concentration. To our knowledge, no study has investigated the other selected SNP (CYP24A1 rs4809958, RXR rs7861779 and rs12004589 and CaSR rs4678174) in relation to prostate cancer risk. Besides, other vitamin D-related SNP than the ones included in the present study may also be associated with prostate cancer risk, as observed by Mondul et al.(14), and deserve further investigation. Plasma PTH concentration was not associated with the risk of prostate cancer. To our knowledge, our study was only the second to investigate this relationship, the first one having observed null results(9). In a previous study performed in the SU.VI.MAX cohort(22), we observed an inverse correlation between 25(OH)D and PTH concentrations, with a threshold value for PTH when 25(OH)D was approximately 30 ng/ml. Thus, it could be expected that PTH concentration would decrease as 25(OH)D concentration increases. Mechanistic data are unclear regarding a potential involvement of PTH in prostate carcinogenesis. Although some data have suggested a potential pro-carcinogenic role of PTH(40–42) (potential mitogenic activity in preneoplastic lesions), others support a potential protective role. Indeed, high PTH concentration may decrease growth hormone secretion, thereby decreasing circulating insulin-like growth factor-1 (IGF-1) concentration(43,44); IGF-1 being considered as a potential risk factor for prostate cancer(45,46). Thus, further investigation is needed on the association between PTH concentration and prostate cancer risk. Strengths of our study pertained to its prospective design, long follow-up, simultaneous assessment of 25(OH)D and PTH plasma concentrations, vitamin D-related gene polymorphisms and dietary intakes, and the consideration of numerous confounding factors. However, limitations should be acknowledged. First, blood Ca concentration was not available in our study. Ca concentration would have provided more information regarding the association between 25(OH)D, PTH, Ca and prostate cancer risk. Dietary Ca intake was available, but intakes within normal range are poorly correlated with blood Ca concentration(47), which is under homoeostatic control. Second, only one plasma 25(OH)D and PTH measurement was available at baseline. Repeated measures could have been of interest to study their evolution across time. Third, although the number of cases was appropriate for the analyses described here, it has limited our ability to perform separate analyses in specific subgroups, in particular regarding genetic polymorphisms or prostate cancer grade. Finally, the observed inverse association between vitamin D status and prostate cancer could be partly explained by reverse causality, considering the long lasting development of this cancer. However, results were similar when excluding cases diagnosed within the first 5 years of follow-up, thus arguing against reverse causality. In this prospective study, the association between vitamin D and prostate cancer risk was addressed through 25(OH)D concentration, polymorphisms of vitamin D-related genes and PTH concentration. Prostate cancer risk was inversely associated with 25(OH)D concentration but not with PTH concentration. These results, supported by mechanistic data, bring a new contribution to the understanding of the relationship between vitamin D and prostate cancer risk and deserve further exploration. ------  Am J Clin Nutr. 2015 Jan;101(1):87-117. doi: 10.3945/ajcn.113.067157. Epub 2014 Nov 19. Dairy products, calcium, and prostate cancer risk: a systematic review and meta-analysis of cohort studies. Aune D(1), Navarro Rosenblatt DA(1), Chan DS(1), Vieira AR(1), Vieira R(1), Greenwood DC(1), Vatten LJ(1), Norat T(1). Author information: (1)From the Department of Public Health and General Practice, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway (DA and LJV); the Department of Epidemiology and Public Health, Imperial College, London, United, Kingdom (DA, DANR, DSMC, ARV, RV, and TN); and the Biostatistics Unit, Centre for Epidemiology and Biostatistics, University of Leeds, Leeds, United Kingdom (DCG). BACKGROUND: Dairy product and calcium intakes have been associated with increased prostate cancer risk, but whether specific dairy products or calcium sources are associated with risk is unclear. OBJECTIVE: In the Continuous Update Project, we conducted a meta-analysis of prospective studies on intakes of dairy products and calcium and prostate cancer risk. DESIGN: PubMed and several other databases were searched up to April 2013. Summary RRs were estimated by using a random-effects model. RESULTS: Thirty-two studies were included. Intakes of total dairy products [summary RR: 1.07 (95% CI: 1.02, 1.12; n = 15) per 400 g/d], total milk [summary RR: 1.03 (95% CI: 1.00, 1.07; n = 14) per 200 g/d], low-fat milk [summary RR: 1.06 (95% CI: 1.01, 1.11; n = 6) per 200 g/d], cheese [summary RR: 1.09 (95% CI: 1.02, 1.18; n = 11) per 50 g/d], and dietary calcium [summary RR: 1.05 (95% CI: 1.02, 1.09; n = 15) per 400 mg/d] were associated with increased total prostate cancer risk. Total calcium and dairy calcium intakes, but not nondairy calcium or supplemental calcium intakes, were also positively associated with total prostate cancer risk. Supplemental calcium was associated with increased risk of fatal prostate cancer. CONCLUSIONS: High intakes of dairy products, milk, low-fat milk, cheese, and total, dietary, and dairy calcium, but not supplemental or nondairy calcium, may increase total prostate cancer risk. The diverging results for types of dairy products and sources of calcium suggest that other components of dairy rather than fat and calcium may increase prostate cancer risk. Any additional studies should report detailed results for subtypes of prostate cancer. © 2015 American Society for Nutrition. PMID: 25527754