Vitamin D and Reduced Risk of Breast Cancer: A Population-Based Case-Control Study The effect of various vitamin D supplementation regimens in breast cancer patients Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Calcium plus vitamin D supplementation and the risk of colorectal cancer. Monthly High-Dose Vitamin D Supplementation and Cancer Risk: A Post Hoc Analysis of the Vitamin D Assessment Randomized Clinical Trial Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial Interaction between current vitamin D supplementation and menopausal hormone therapy use on breast cancer risk: evidence from the E3N cohort. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease Postmenopausal breast cancer risk and interactions between body mass index, menopausal hormone therapy use, and vitamin D supplementation: Evidence from the E3N cohort. Serum Vitamin D and Risk of Breast Cancer within Five Years The D-Health Trial: A randomized trial of vitamin D for prevention of mortality and cancer. Vitamin D and calcium intakes and breast cancer risk in pre- and postmenopausal women. Calcium, vitamin D, dairy products, and risk of colorectal cancer in the Cancer Prevention Study II Nutrition Cohort (United States) The Effect of Calcium plus Vitamin D on Risk for Invasive Cancer: Results of the Women's Health Initiative (WHI) Calcium Plus Vitamin D Randomized Clinical Trial Vitamin D3 supplementation at 4000 international units per day for one year results in a decrease of positive cores at repeat biopsy in subjects with low-risk prostate cancer under active surveillance. Total and cancer mortality after supplementation with vitamins and minerals: follow-up of the Linxian General Population Nutrition Intervention Trial.
Background : Vitamin D , antiproliferative and proapoptotic in breast cancer cell lines , can reduce the development of mammary tumors in carcinogen-exposed rats . Current evidence in humans is limited with some suggestion that vitamin D – related factors may reduce the risk of breast cancer . We conducted a population -based case-control study to assess the evidence for a relationship between sources of vitamin D and breast cancer risk . Methods : Women with newly diagnosed invasive breast cancer were identified from the Ontario Cancer Registry . Women without breast cancer were identified through r and omly selected residential telephone numbers . Telephone interviews were completed for 972 cases and 1,135 controls .  Odds ratios ( OR ) and 95 % confidence intervals ( CI ) for vitamin D – related variables were estimated using unconditional logistic regression with adjustment for potential confounders . Results : Reduced breast cancer risks were associated with increasing sun exposure from ages 10 to 19 ( e.g. , OR , 0.65 ; 95 % CI , 0.50 - 0.85 for the highest quartile of outdoor activities versus the lowest ; P for trend = 0.0006 ) . Reduced risk was also associated with cod liver oil use ( OR , 0.76 ; 95 % CI , 0.62 - 0.92 ) and increasing milk consumption ( OR , 0.62 95 % CI 0.45 - 0.86 for ≥10 glasses per week versus none ; P for trend = 0.0004 ) . There was weaker evidence for associations from ages 20 to 29 and no evidence for ages 45 to 54 . Conclusion : We found strong evidence to support the hypothesis that vitamin D could help prevent breast cancer . However , our results suggest that exposure earlier in life , particularly during breast development , maybe most relevant . These results should be confirmed . ( Cancer Epidemiol Biomarkers Prev 2007;16(3):422–9 Vitamin D deficiency in the patients treated for breast cancer is associated with numerous adverse effects ( bone loss , arthralgia , and falls ) . The first aim of this study was to assess vitamin D status , determined by 25-OH vitamin D levels , among women diagnosed with breast cancer according to demographic/ clinical variables and bone mineral density ( BMD ) . The second aim of this study was to evaluate the effect of daily low-dose and weekly high-dose vitamin D supplementation on 25-OH vitamin D levels . This retrospective study included 224 women diagnosed with stage 0–III breast cancer who received treatment at the James P. Wilmot Cancer Center at the University of Rochester Medical Center . Total 25-OH vitamin D levels ( D2 + D3 ) were determined at baseline for all participants . Vitamin D deficiency was defined as a 25-OH vitamin D level < 20 ng/ml , insufficiency as 20–31 ng/ml , and sufficiency as ≥32 ng/ml . BMD was assessed during the period between 3 months before and 6 months following the baseline vitamin D assessment . Based on the participants ’ baseline levels , they received either no supplementation , low-dose supplementation ( 1,000 IU/day ) , or high-dose supplementation ( ≥50,000 IU/week ) , and 25-OH vitamin D was reassessed in the following 8–16 weeks . Approximately 66.5 % had deficient/insufficient vitamin D levels at baseline . Deficiency/insufficiency was more common among non-Caucasians , women with later-stage disease , and those who had previously received radiation therapy ( P < 0.05 ) . Breast cancer patients with deficient/insufficient 25-OH vitamin D levels had significantly lower lumbar BMD ( P = 0.03 ) . Compared to the no-supplementation group , weekly high-dose supplementation significantly increased 25-OH vitamin D levels , while daily low-dose supplementation did not significantly increase levels . Vitamin D deficiency and insufficiency were common among women with breast cancer and associated with reduced BMD in the spine . Clinicians should carefully consider vitamin D supplementation regimens when treating vitamin D deficiency/insufficiency in breast cancer patients BACKGROUND Vitamin D has potent anticancer properties , especially against digestive-system cancers . Many human studies have used geographic residence as a marker of solar ultraviolet B and hence vitamin D exposure . Here , we considered multiple determinants of vitamin D exposure ( dietary and supplementary vitamin D , skin pigmentation , adiposity , geographic residence , and leisure-time physical activity-to estimate sunlight exposure ) in relation to cancer risk in the Health Professionals Follow-Up Study . METHODS Among 1095 men of this cohort , we quantified the relation of these six determinants to plasma  25-hydroxy-vitamin D [ 25(OH)D ] level by use of a multiple linear regression model . We used results from the model to compute a predicted 25(OH)D level for each of 47,800 men in the cohort based on these characteristics . We then prospect ively examined this variable in relation to cancer risk with multivariable Cox proportional hazards models . RESULTS From 1986 through January 31 , 2000 , we documented 4286 incident cancers ( excluding organ-confined prostate cancer and nonmelanoma skin cancer ) and 2025 deaths from cancer . From multivariable models , an increment of 25 nmol/L in predicted 25(OH)D level was associated with a 17 % reduction in total cancer incidence ( multivariable relative risk [ RR ] = 0.83 , 95 % confidence interval [ CI ] = 0.74 to 0.92 ) , a 29 % reduction in total cancer mortality ( RR = 0.71 , 95 % CI = 0.60 to 0.83 ) , and a 45 % reduction in digestive-system cancer mortality ( RR = 0.55 , 95 % CI = 0.41 to 0.74 ) . The absolute annual rate of total cancer was 758 per 100,000 men in the bottom decile of predicted 25(OH)D and 674 per 100,000 men for the top decile ; these respective rates were 326 per 100,000 and 277 per 100,000 for total cancer mortality and 128 per 100,000 and 78 per 100,000 for digestive-system cancer mortality . Results were similar when we controlled further for body mass index or physical activity level . CONCLUSIONS Low levels of vitamin D may be associated with increased cancer incidence and mortality in men , particularly for digestive-system cancers . The vitamin D supplementation necessary to achieve a 25(OH)D increment of 25 nmol/L may be at least 1500 IU/day BACKGROUND Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers . However , interventional studies to test this effect are lacking . OBJECTIVE The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk  of all types . DESIGN This was a 4-y , population -based , double-blind , r and omized placebo-controlled trial . The primary outcome was fracture incidence , and the principal secondary outcome was cancer incidence . The subjects were 1179 community-dwelling women r and omly selected from the population of healthy postmenopausal women aged > 55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were r and omly assigned to receive 1400 - 1500 mg supplemental calcium/d alone ( Ca-only ) , supplemental calcium plus 1100 IU vitamin D3/d ( Ca + D ) , or placebo . RESULTS When analyzed by intention to treat , cancer incidence was lower in the Ca + D women than in the placebo control subjects ( P < 0.03 ) . With the use of logistic regression , the unadjusted relative risks ( RR ) of incident cancer in the Ca + D and Ca-only groups were 0.402 ( P = 0.01 ) and 0.532 ( P = 0.06 ) , respectively . When analysis was confined to cancers diagnosed after the first 12 mo , RR for the Ca + D group fell to 0.232 ( CI : 0.09 , 0.60 ; P < 0.005 ) but did not change significantly for the Ca-only group . In multiple logistic regression models , both treatment and serum 25-hydroxyvitamin D concentrations were significant , independent predictors of cancer risk . CONCLUSIONS Improving calcium and vitamin D nutritional status substantially reduces  all-cancer risk in postmenopausal women . This trial was registered at clinical trials.gov as NCT00352170 BACKGROUND Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials . However , r and omized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking . METHODS We conducted a r and omized , double-blind , placebo-controlled trial involving 36,282 postmenopausal women from 40 Women 's Health Initiative centers : 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [ corrected ] twice daily ( 1000 mg of elemental calcium and 400 IU of vitamin D3 ) and 18,106 received a matching placebo for an average of 7.0 years . The incidence of pathologically confirmed colorectal cancer was the design ated secondary outcome . Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study . RESULTS The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo ( 168 and 154 cases ; hazard ratio , 1.08 ; 95 percent confidence interval , 0.86 to 1.34 ; P=0.51 ) , and the tumor characteristics were similar in the two groups . The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups . There were no significant treatment interactions with baseline characteristics . CONCLUSIONS Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer  among postmenopausal women . The long latency associated with the development of colorectal cancer , along with the seven-year duration of the trial , may have contributed to this null finding . Ongoing follow-up will assess the longer-term effect of this intervention . ( Clinical Trials.gov number , NCT00000611 . ) Importance Previous r and omized clinical trials have reported inconsistent results on the effect of vitamin D supplementation on cancer incidence . Objective To examine whether high-dose vitamin D supplementation received monthly , without calcium , is associated with a reduction in  cancer incidence and cancer mortality in the general population . Design , Setting , and Participants This is a post hoc analysis of data from the Vitamin D Assessment ( ViDA ) study , a r and omized , double-blind , placebo-controlled trial that recruited participants from family practice s and community groups in Auckl and , New Zeal and , from April 5 , 2011 , through November 6 , 2012 , with follow-up completed December 31 , 2015 . Participants were adult community residents aged 50 to 84 years . Of 47 905 adults invited from family practice s and 163 from community groups , 5110 participants were r and omized to receive vitamin D3 ( n = 2558 ) or placebo ( n = 2552 ) . Two participants withdrew consent , and all others ( n = 5108 ) were included in the primary analysis . Data analysis was by intention to treat . Interventions Oral vitamin D3 , in an initial bolus dose of 200 000 IU and followed by monthly doses of 100 000 IU , or placebo for a median of 3.3 years ( range , 2.5 - 4.2 years ) . Main Outcomes and Measures Post hoc primary outcome was the number of all primary invasive and in situ malignant neoplasms ( excluding nonmelanoma skin cancers ) diagnosed from r and omization until the study medication was discontinued on July 31 , 2015 . Results Of the 5108 participants included in the analysis , the mean ( SD ) age was 65.9 ( 8.3 ) years , 58.1 % were male , and 4253 ( 83.3 % ) were of European or another race/ethnicity , with the remainder being Polynesian or South Asian .  Mean ( SD ) baseline deseasonalized 25-hydroxyvitamin D concentration was 26.5 ( 9.0 ) ng/mL. In a r and om sample of 438 participants , the mean follow-up 25-hydroxyvitamin D concentration consistently was greater than 20 ng/mL higher in the vitamin D group than in the placebo group . The primary outcome of cancer comprised 328 total cases of cancer ( 259 invasive and 69 in situ malignant neoplasms ) and occurred in 165 of 2558 participants ( 6.5 % ) in the vitamin D group and 163 of 2550 ( 6.4 % ) in the placebo group , yielding an adjusted hazard ratio of 1.01 ( 95 % CI , 0.81 - 1.25 ; P = .95 ) . Conclusions and Relevance High-dose vitamin D supplementation prescribed monthly for up to 4 years without calcium may not prevent cancer . This study suggests that daily or weekly dosing for a longer period may require further study . Trial Registration anzctr.org.au Identifier : Importance Evidence suggests that low vitamin D status may increase the risk of cancer . Objective To determine if dietary supplementation with vitamin D3 and calcium reduces the risk of  cancer among older women . Design , Setting , and Participants A 4-year , double-blind , placebo-controlled , population -based r and omized clinical trial in 31 rural counties ( June 24 , 2009 , to August 26 , 2015—the final date of follow-up ) . A total of 2303 healthy postmenopausal women 55 years or older were r and omized , 1156 to the treatment group and 1147 to the placebo group . Duration of treatment was 4 years . Interventions The treatment group ( vitamin D3 + calcium group ) received 2000 IU/d of vitamin D3 and 1500 mg/d of calcium ; the placebo group received identical placebos . Main Outcomes and Measures The primary outcome was the incidence of all-type cancer ( excluding nonmelanoma skin cancers ) , which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling . Results Among 2303 r and omized women ( mean age , 65.2 years [ SD , 7.0 ] ; mean baseline serum 25-hydroxyvitamin D level , 32.8 ng/mL [ SD , 10.5 ] ) , 2064 ( 90 % ) completed the study . At year 1 , serum 25-hydroxyvitamin D levels were 43.9 ng/mL in the vitamin D3 + calcium group and 31.6 ng/mL in the placebo group . A new diagnosis of cancer was confirmed in 109 participants , 45 ( 3.89 % ) in the vitamin D3 + calcium group and 64 ( 5.58 % ) in the placebo group ( difference , 1.69 % [ 95 % CI , −0.06 % to 3.46 % ] ; P = .06 ) . Kaplan-Meier incidence over 4 years was 0.042 ( 95 % CI , 0.032 to 0.056 ) in the vitamin D3 + calcium group and 0.060 ( 95 % CI , 0.048 to 0.076 ) in the placebo group ; P = .06 . In unadjusted Cox proportional hazards regression , the hazard ratio was 0.70 ( 95 % CI , 0.47 to 1.02 ) . Adverse events potentially related to the study included renal calculi ( 16 participants in the vitamin D3 + calcium group and 10 in the placebo group ) , and elevated serum calcium levels ( 6 in the vitamin D3 + calcium group and 2 in the placebo group ) . Conclusions and Relevance Among healthy postmenopausal older women with a mean baseline serum 25-hydroxyvitamin D level of 32.8 ng/mL , supplementation with vitamin D3 and calcium compared with placebo did not result in a significantly lower risk of all-type cancer at 4 years . Further research is necessary to assess the possible role of vitamin D in cancer prevention . Trial Registration clinical trials.gov Identifier : BACKGROUND Experimental studies suggest protective effects of vitamin D on breast carcinogenesis , particularly on estrogen receptor-positive tumors . Epidemiologic data are less conclusive . OBJECTIVE Our objective was to investigate the association between postmenopausal breast cancer risk and current or past vitamin D supplementation overall and according to the use of menopausal hormone therapy ( MHT ) . DESIGN Between 1995 and 2008 , 2482 invasive breast cancer cases were diagnosed among 57,403 postmenopausal women from the E3N prospect i ve cohort during 581,085 person-years .  Vitamin D supplementation was assessed from biennially self-administered question naires sent in 1995 , 2000 , 2002 , and 2005 and from medico-administrative data on drug reimbursements since 2004 . Multivariable HRs for primary invasive breast cancer and 95 % CIs were estimated by using Cox models . RESULTS A decreased postmenopausal breast cancer risk was associated with current ( HR : 0.82 ; 95 % CI : 0.69 , 0.97 ) but not past ( HR : 1.10 ; 95 % CI : 0.92 , 1.31 ) vitamin D supplementation ( P-homogeneity = 0.02 ) . The association with current vitamin D supplementation  differed according to MHT use : ever users ( HR : 0.74 ; 95 % CI : 0.60 , 0.90 ) and never users ( HR : 1.13 ; 95 % CI : 0.89 , 1.56 ) ; P-homogeneity = 0.02 . CONCLUSIONS In this observational study , current vitamin D supplementation , mostly taken daily and combined with calcium , was associated with a decreased postmenopausal breast cancer risk in MHT users . These findings should be confirmed before considering vitamin D supplementation to partly balance the MHT-associated increased breast cancer risk BACKGROUND It is unclear whether supplementation with vitamin D reduces the risk of cancer or cardiovascular disease , and data from r and omized trials are limited . METHODS We conducted a nationwide , r and omized , placebo‐controlled trial , with a two‐by‐two factorial design , of vitamin D3 ( cholecalciferol ) at a dose of 2000 IU per day and marine n‐3 ( also called omega‐3 ) fatty acids at a dose of 1 g per day for the prevention of cancer and cardiovascular disease among men 50 years of age or older and women 55 years of age or older in the United States . Primary end points were invasive cancer of any type and major cardiovascular events ( a composite of myocardial infa rct ion , stroke , or death from cardiovascular causes ) . Secondary end points included site‐specific cancers , death from cancer , and additional cardiovascular events . This article reports the results of the comparison of vitamin D with placebo . RESULTS A total of 25,871 participants , including 5106 black participants , underwent r and omization . Supplementation with vitamin D was not associated with a lower risk of either of the primary end points . During a median follow‐up of 5.3 years , cancer was diagnosed in 1617 participants ( 793 in the vitamin D group and 824 in the placebo group ; hazard ratio , 0.96 ; 95 % confidence interval [ CI ] , 0.88 to 1.06 ; P=0.47 ) . A major cardiovascular event occurred in 805 participants ( 396 in the vitamin D group and 409 in the placebo group ; hazard ratio , 0.97 ; 95 % CI , 0.85 to 1.12 ; P=0.69 ) . In the analyses of secondary end points , the hazard ratios were as follows : for death from cancer ( 341 deaths ) , 0.83 ( 95 % CI , 0.67 to 1.02 ) ; for breast cancer , 1.02 ( 95 % CI , 0.79 to 1.31 ) ; for prostate cancer , 0.88 ( 95 % CI , 0.72 to 1.07 ) ; for colorectal cancer , 1.09 ( 95 % CI , 0.73 to 1.62 ) ; for the exp and ed composite end point of major cardiovascular events plus coronary revascularization , 0.96 ( 95 % CI , 0.86 to 1.08 ) ; for myocardial infa rct ion , 0.96 ( 95 % CI , 0.78 to 1.19 ) ; for stroke , 0.95 ( 95 % CI , 0.76 to 1.20 ) ; and for death from cardiovascular causes , 1.11 ( 95 % CI , 0.88 to 1.40 ) . In the analysis of death from any cause ( 978 deaths ) , the hazard ratio was 0.99 ( 95 % CI , 0.87 to 1.12 ) . No excess risks of hypercalcemia or other adverse events were identified . CONCLUSIONS Supplementation with vitamin D did not result in a lower incidence of invasive cancer or cardiovascular events than placebo . ( Funded by the National Institutes of Health and others ; VITAL Clinical Trials.gov number , NCT01169259 . Experimental studies suggest protective effects of vitamin D on breast carcinogenesis , but epidemiological evidence is not conclusive . Body mass index ( BMI ) has been shown to modulate the effect of supplementation on the vitamin D status , but its potential influence on the relationship with breast cancer risk has been little studied . We investigated a potential interaction between BMI and vitamin D supplementation  on breast cancer risk while considering an already reported interaction between vitamin D supplementation and menopausal hormone therapy ( MHT ) use . Vitamin D supplementation was prospect ively investigated in 57,403 postmenopausal women from the French E3N cohort including 2,482 incident breast cancer cases diagnosed between 1995 and 2008 .  Multivariable hazard ratios ( HR ) for primary invasive breast cancer and 95 % confidence intervals ( CI ) were estimated using Cox models . Among MHT ever users , vitamin D supplementation was associated with decreased breast cancer risk , similarly across BMI strata ( Phomogeneity = 0.83 ) . Among MHT never users , ever vitamin D supplementation was associated with increased postmenopausal breast cancer risk in women with baseline BMI < 25 kg/m(2 ) ( HR = 1.51 , 95 % CI : 1.13 , 2.02 ) , but not in women with higher BMI ( 0.98 , 95 % CI : 0.62 , 1.56 ) , Phomogeneity = 0.12 . In conclusion , our findings suggest that vitamin D supplementation may reduce the excess breast cancer risk in MHT users , but draw attention on a potential risk in postmenopausal women not exposed to high exogenous or endogenous hormones , i.e. non-overweight MHT-non users , especially in the present context of increasing vitamin D supplement use and decreasing MHT use Background : Vitamin D is an environmental and dietary agent with known anticarcinogenic effects , but protection against breast cancer has not been established . Objective : We evaluated the association between baseline serum 25-hydroxyvitamin D [ 25(OH)D ] levels , supplemental vitamin D use , and breast cancer incidence over the subsequent 5 y of follow-up . Methods : From 2003–2009 , the Sister Study enrolled 50,884 U.S. women 35–74 y old who had a sister with breast cancer but had never had breast cancer themselves . Using liquid chromatography – mass spectrometry , we measured 25(OH)D in serum sample s from 1,611 women who later developed breast cancer and from 1,843 r and omly selected cohort participants . We estimated hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for the risk of developing breast cancer using Cox proportional hazards models . Results : We found that 25(OH)D levels > 38.0 ng/mL were associated with a 21 % lower breast cancer hazard ( highest versus lowest quartile : adjusted HR=0.79 ; CI : 0.63 , 0.98 ) . Analysis of the first 5 y of follow-up for all 50,884 Sister Study participants showed that self-reported vitamin D supplementation ≥4 times/wk was associated with an 11 % lower hazard [ HR=0.89 ( CI : 0.81 , 0.99 ) ] . These associations were particularly strong among postmenopausal women [ HR=0.72 ( CI : 0.57 , 0.93 ) and HR=0.83 ( CI : 0.74 , 0.93 ) , respectively ] . Conclusions : In this cohort of women with elevated risk , high serum 25(OH)D levels  and regular vitamin D supplement use were associated with lower rates of incident , postmenopausal breast cancer over 5 y of follow-up . These results may help to establish clinical benchmarks for 25(OH)D levels ; in addition , they support the hypothesis that vitamin D supplementation is useful in breast cancer prevention . BACKGROUND Vitamin D , specifically serum 25(OH)D has been associated with mortality , cancer and multiple other health endpoints in observational studies , but there is a paucity of clinical trial evidence sufficient to determine the safety and effectiveness of population -wide supplementation . We have therefore launched the D-Health Trial , a r and omized trial of vitamin D supplementation for prevention of mortality and cancer . Here we report the methods and describe the trial cohort . METHODS The D-Health Trial is a r and omized placebo-controlled trial , with planned intervention for 5years and a further 5years of passive follow-up through linkage with health and death registers . Participants aged 65 - 84years were recruited from the general population of Australia . The intervention is monthly oral doses of 60,000IU of cholecalciferol or matching placebo . The primary outcome is all-cause mortality . Secondary outcomes are total cancer incidence and colorectal cancer incidence . RESULTS We recruited 21,315 participants to the trial between February 2014 and May 2015 . The participants in the two arms of the trial were well-balanced at baseline . Comparison with Australian population statistics shows that the trial participants were less likely to report being in fair or poor health , to be current smokers or to have diabetes than the Australian population . However , the proportion overweight or with health conditions such as arthritis and angina was similar . CONCLUSIONS Observational data can not be considered sufficient to support interventions delivered at a population level . Large-scale r and omized trials such as the D-Health Trial are needed to inform public health policy and practice BACKGROUND Some evidence suggests that vitamin D may reduce  breast cancer risk . Despite the biological interaction between vitamin D and calcium , few studies have evaluated their joint effects on breast cancer risk . OBJECTIVE The objective was to evaluate the associations and potential interaction between vitamin D and calcium ( from food and supplements ) and breast cancer risk in a population -based case-control study . DESIGN Breast cancer cases aged 25 - 74 y ( diagnosed 2002 - 2003 ) were identified through the Ontario Cancer Registry . Controls were identified by using r and om digit dialing ; 3101 cases and 3471 controls completed epidemiologic and food-frequency question naires . Adjusted odds ratios ( ORs ) and 95 % CIs were estimated by using multivariate logistic regression . RESULTS Vitamin D and calcium intakes from food only and total combined intakes ( food and supplements ) were not associated with breast cancer risk , although the mean intake of vitamin D was low . Vitamin D supplement intake > 10 microg/d ( 400 IU/d ) compared with no intake was associated with a reduced risk of breast cancer ( adjusted OR : 0.76 ; 95 % CI : 0.59 , 0.98 ) . No categories of calcium supplement intake were significantly associated with reduced breast cancer risk , but a significant inverse trend was observed ( P = 0.04 ) . There were no significant interactions involving vitamin D , calcium , or menopausal status . CONCLUSIONS No associations were found between overall vitamin D or calcium intake and breast cancer risk .  Vitamin D from supplements was independently associated with reduced breast cancer risk . Further research is needed to investigate the effects of higher doses of vitamin D and calcium supplements Objective : Calcium , vitamin D , and dairy product intake may reduce the risk of colorectal cancer . We therefore examined the association between these factors and risk of colorectal cancer in a large prospect i ve cohort of United States men and women . Methods : Participants in the Cancer Prevention Study II Nutrition Cohort completed a detailed question naire on diet , medical history , and lifestyle in 1992–93 . After excluding participants with a history of cancer or incomplete dietary information , 60,866 men and 66,883 women remained for analysis . During follow-up through 31 August 1997 we documented 421 and 262 cases of incident colorectal cancers among men and women , respectively . Multivariate-adjusted rate ratios ( RR ) were calculated using Cox proportional hazards models . Results :  Total calcium  intake ( from diet and supplements ) was associated with marginally lower colorectal cancer risk in men and women ( RR = 0.87 , 95 % CI 0.67–1.12 , highest vs lowest quintiles , p trend = 0.02 ) . The association was strongest for calcium from supplements ( RR = 0.69 , 95 % CI 0.49–0.96 for ≥500 mg/day vs none ) . Total vitamin D intake ( from diet and multivitamins ) was also inversely associated with risk of colorectal cancer , particularly among men ( RR = 0.71 , 95 % CI 0.51–0.98 , p trend = 0.02  ) .  Dairy product intake was not related to overall risk . Conclusions : Our results support the hypothesis that calcium modestly reduces risk of colorectal cancer . Vitamin D was associated with reduced risk of colorectal cancer only in men In the Women 's Health Initiative ( WHI ) trial of calcium plus vitamin D ( CaD ) , we examined the treatment effect on incidence and mortality for all invasive cancers . Postmenopausal women ( N = 36,282 ) were r and omized to 1,000 mg of elemental calcium with 400 IU vitamin D3 or placebo . Cox models estimated risk of cancer incidence and mortality . After 7.0 yr , 1,306 invasive cancers were diagnosed in the supplement and 1,333 in the placebo group [ hazard ratio ( HR ) = 0.98 ; CI = 0.90 , 1.05 , unweighted P = 0.54 ] . Mortality did not differ between supplement ( 315 , annualized% = .26 ) and placebo [ ( 347 , 0.28 % ; P = 0.17 ; HR = 0.90 ( 0.77 , 1.05 ) ] . Significant treatment interactions on incident cancer were found for family history of cancer , personal total intake of vitamin D , smoking , and WHI dietary trial r and omized group . Calcium/vitamin D supplementation did not reduce invasive cancer incidence or mortality . Supplementation lowered cancer risk in the WHI healthy diet trial arm and in women without a first-degree relative with cancer . The interactions are only suggestive given multiple testing considerations . The low vitamin D dose provided , limited adherence , and lack of serum 25(OH)D values should be considered when interpreting these findings CONTEXT We wanted to investigate vitamin D in low-risk prostate cancer . OBJECTIVES The objective of the study was to determine whether vitamin D(3 ) supplementation at 4000 IU/d for 1 yr is safe and would result in a decrease in serum levels of prostate-specific antigen ( PSA ) or in the rate of progression . DESIGN In this open-label clinical trial ( Investigational New Drug 77,839 ) , subjects were followed up until repeat biopsy . SETTING All subjects were enrolled through the Medical University of South Carolina and the Ralph H. Johnson Veterans Affairs Medical Center , both in Charleston , SC . PATIENTS AND OTHER PARTICIPANTS All subjects had a diagnosis of low-risk prostate cancer . Fifty-two subjects were enrolled in the study , 48 completed 1 yr of supplementation , and 44 could be analyzed for both safety and efficacy objectives . INTERVENTION The intervention included vitamin D(3 ) soft gels ( 4000 IU ) . MAIN OUTCOME MEASURES Adverse events were monitored throughout the study . PSA serum levels were measured at entry and every 2 months for 1 yr . Biopsy procedures were performed before enrollment ( for eligibility ) and after 1 yr of supplementation . RESULTS No adverse events associated with vitamin D(3 ) supplementation were observed . No significant changes in PSA levels were observed . However , 24 of 44 subjects ( 55 % ) showed a decrease in the number of positive cores or decrease in Gleason score ; five subjects ( 11 % ) showed no change ; 15 subjects ( 34 % ) showed an increase in the number of positive cores or Gleason score .  CONCLUSION Patients with low-risk prostate cancer under active surveillance may benefit from vitamin D(3 ) supplementation at 4000 IU/d BACKGROUND The General Population Nutrition Intervention Trial was a r and omized primary esophageal and gastric cancer prevention trial conducted from 1985 to 1991 , in which 29,584 adult participants in Linxian , China , were given daily vitamin and mineral supplements . Treatment with " factor D , " a combination of 50 microg selenium , 30 mg vitamin E , and 15 mg beta-carotene , led to decreased mortality from all causes , cancer overall , and gastric cancer . Here , we present 10-year follow-up after the end of active intervention . METHODS Participants were assessed by periodic data collection , monthly visits by village health workers , and quarterly review of the Linxian Cancer Registry . Hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for the cumulative effects of four vitamin and mineral supplementation regimens were calculated using adjusted proportional hazards models . RESULTS Through May 31 , 2001 , 276 participants were lost to follow-up ; 9727 died , including 3242 from cancer ( 1515 from esophageal cancer and 1199 from gastric cancer ) . Participants who received factor D had lower overall mortality ( HR = 0.95 , 95 % CI = 0.91 to 0.99 ; P = .009 ; reduction in cumulative mortality from 33.62 % to 32.19 % ) and gastric cancer mortality ( HR = 0.89 , 95 % CI = 0.79 to 1.00 ; P = .043 ; reduction in cumulative gastric cancer mortality from 4.28 % to 3.84 % ) than subjects who did not receive factor D. Reductions were mostly attributable to benefits to subjects younger than 55 years . Esophageal cancer deaths between those who did and did not receive factor D were not different overall ; however , decreased 17 % among participants younger than 55 ( HR = 0.83 , 95 % CI = 0.71 to 0.98 ; P = .025 ) but increased 14 % among those aged 55 years or older ( HR = 1.14 , 95 % CI = 1.00 to 1.30 ; P = .047 ) [ corrected ] . Vitamin A and zinc supplementation was associated with increased total and stroke mortality ; vitamin C and molybdenum supplementation , with decreased stroke mortality . CONCLUSION The beneficial effects of selenium , vitamin E , and beta-carotene on mortality were still evident up to 10 years after the cessation of supplementation and were consistently greater in younger participants . Late effects of other supplementation regimens were also observed
There is currently no firm evidence that vitamin D supplementation decreases or increases cancer occurrence in predominantly elderly community-dwelling women .
Vitamin D₃ supplementation  decreased cancer mortality  and vitamin D supplementation  decreased all-cause mortality , but these estimates are at risk of type I errors due to the fact that too few participants were examined , and to risks of attrition bias originating from substantial dropout of participants .
Combined vitamin D₃ and calcium supplements  increased nephrolithiasis , whereas it remains unclear from the included trials whether vitamin D₃ , calcium , or both were responsible for this effect .
BACKGROUND The evidence on whether vitamin D supplementation is effective in decreasing cancers is contradictory .
OBJECTIVES To assess the beneficial and harmful effects of vitamin D supplementation for prevention of cancer in adults .