***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 Objective Low serum 25(OH)D levels are associated with cardiovascular risk factors , and also predict future myocardial infa rct ion ( MI ) , type 2 diabetes ( T2DM ) , cancer and all-cause mortality . Recently several single nucleotide polymorphisms ( SNPs ) associated with serum 25-hydroxyvitamin D ( 25(OH)D ) level have been identified . If these relations are causal one would expect a similar association between these SNPs and health . Methods DNA was prepared from subjects who participated in the fourth survey of the Tromsø Study in 1994–1995 and who were registered with the endpoints MI , T2DM , cancer or death as well as a r and omly selected control group . The endpoint registers were complete up to 2007–2010 . Genotyping was performed for 17 SNPs related to the serum 25(OH)D level . Results A total of 9528 subjects were selected for genetic analyses which were successfully performed for at least one SNP in 9471 subjects . Among these , 2025 were registered with MI , 1092 with T2DM , 2924 with cancer and 3828 had died . The mean differences in serum 25(OH)D levels between SNP genotypes with the lowest and highest serum 25(OH)D levels varied from 0.1 to 7.8 nmol/L. A genotype score based on weighted risk alleles regarding low serum 25(OH)D levels was established . There was no consistent association between the genotype score or individuals SNPs and MI , T2DM , cancer , mortality or risk factors for disease . However , for rs6013897 genotypes ( located at the 24-hydroxylase gene ( CYP24A1 ) ) there was a significant association with breast cancer ( P<0.05 ) . Conclusion Our results do not support nor exclude a causal relationship between serum 25(OH)D levels and MI , T2DM , cancer or mortality , and our observation on breast cancer needs confirmation . Further genetic studies are warranted , particularly in population s with vitamin D deficiency . Trial Registration Clinical Trials.gov Sun exposure is associated with lower death rates for pancreatic cancer in some ecological studies . Skin exposure to UVB light induces cutaneous production of precursors to 25-hydroxyvitamin D [ 25(OH)D ] . Pancreatic islet and duct cells express 25(OH)D(3)-1alpha-hydroxylase that generates the biologically active 1,25(OH)(2 ) vitamin D form . Thus , 25(OH)D concentrations could affect pancreatic function and possibly pancreatic cancer etiology . We conducted a prospect i ve nested case-control study in the Alpha-Tocopherol , Beta-Carotene Cancer Prevention cohort of male Finnish smokers , ages 50 to 69 years at baseline , to test whether more adequate vitamin D status , as determined by prediagnostic serum 25(OH)D concentrations , was associated with lower pancreatic cancer risk . Two hundred incident exocrine pancreatic cancer cases that occurred between 1985 and 2001 ( up to 16.7 years of follow-up ) were matched by age and date of blood draw to 400 controls who were alive and free of cancer at the time the case was diagnosed .  Odds ratios ( OR ) and 95 % confidence intervals ( 95 % CI ) were calculated using conditional logistic regression . Higher vitamin D concentrations were associated with a 3-fold increased risk for pancreatic cancer ( highest versus lowest quintile , > 65.5 versus < 32.0 nmol/L : OR , 2.92 ; 95 % CI , 1.56 - 5.48 , P(trend ) = 0.001 ) that remained after excluding cases diagnosed early during follow-up . Contrary to expectations , subjects with higher prediagnostic vitamin D status had an increased pancreatic cancer risk compared with those with lower status . Our findings need to be replicated in other population s and caution is warranted in their interpretation and implication . Our results are intriguing and may provide clues that further the underst and ing of the etiology of this highly fatal cancer Prospect i ve epidemiologic data on the association between vitamin D and mortality are limited , particularly in Asian population s. Among subjects in Linxian , China , the authors aim ed to test whether baseline serum 25-hydroxyvitamin D ( 25(OH)D ) concentrations in a prospect i ve cohort were associated with all-cause mortality and cause-specific mortality rates over 24 years of follow-up ( 1986 - 2010 ) .  Serum 25(OH)D concentrations  were measured in 1,101 subjects  using an immunoassay .  Hazard ratios and 95 % confidence intervals were calculated using Cox regression models that were adjusted for age , sex , tobacco smoking , alcohol drinking , and hypertension . The 25th , 50th , and 75th percentile concentrations of 25(OH)D were 19.6 , 31.9 , and 48.4 nmol/L , respectively . During follow-up , 793 subjects died  , including 279 who died of cerebrovascular accident  , 217 who died of cancer  , and 200 cardiovascular disease deaths . All-cause mortality was not associated with 25(OH)D concentrations using continuous models ( for every 15 nmol/L , hazard ratio = 1.01 , 95 % confidence interval : 0.97 , 1.05 ) or quartile models ( fourth vs. first quartiles , hazard ratio = 1.06 , 95 % confidence interval : 0.87 , 1.30 ; P for trend = 0.731 ) . The authors also found no association with the cause-specific mortality outcomes . Results were similar for men and women . This study showed that prediagnostic serum 25(OH)D concentrations were not associated with all-cause or cause-specific mortality rates in this Chinese population who had low levels of vitamin The beneficial biologic effects attributed to vitamin D suggest a potential to influence overall mortality . Evidence addressing this hypothesis is limited , especially for African Americans who have a high prevalence of vitamin D insufficiency . The authors conducted a nested case-control study within the prospect i ve Southern Community Cohort Study to relate baseline serum levels of 25-hydroxyvitamin D ( 25(OH)D ) with subsequent mortality .  Cases were 1,852 participants who enrolled from 2002 to 2009 and died > 12 months postenrollment . Controls ( n = 1,852 ) were matched on race , sex , age , enrollment site , and blood collection date . The odds ratios for quartile 1 ( < 10.18 ng/mL ) versus quartile 4 ( > 21.64 ng/mL ) levels of 25(OH)D were 1.60 ( 95 % confidence interval ( CI ) : 1.20 , 2.14 ) for African Americans and 2.11 ( 95 % CI : 1.39 , 3.21 ) for non-African Americans . The effects were strongest for circulatory disease death , where quartile 1 versus quartile 4 odds ratios were 2.53 ( 95 % CI : 1.44 , 4.46 ) and 3.25 ( 95 % CI : 1.33 , 7.93 ) for African Americans and non-African Americans , respectively . The estimated odds of total mortality were minimized in the 25(OH)D range of 35 - 40 ng/mL. These findings provide support for the hypothesis that vitamin D status may have an important influence on mortality for both African Americans and non-African Americans Abstract Objective : To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community . Design : R and omised double blind controlled trial of 100 000 IU oral vitamin D3 ( cholecalciferol ) supplementation or matching placebo every four months over five years . Setting and participants : 2686 people ( 2037 men and 649 women ) aged 65 - 85 years living in the general community , recruited from the British doctors register and a general practice register in Suffolk . Main outcome measures : Fracture incidence and total mortality by cause . Results : After five years 268 men and women had incident fractures , of whom 147 had fractures in common osteoporotic sites ( hip , wrist or forearm , or vertebrae ) . Relative risks in the vitamin D group compared with the placebo group were 0.78 ( 95 % confidence interval 0.61 to 0.99 , P=0.04 ) for any first fracture and 0.67 ( 0.48 to 0.93 , P=0.02 ) for first hip , wrist or forearm , or vertebral fracture . 471 participants died . The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 ( 0.74 to 1.06 , P=0.18 ) . Findings were consistent in men and women and in doctors and the general practice population . Conclusion : Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community . What is already known in this topic Vitamin D and calcium supplements are effective in preventing fractures in elderly women Whether isolated vitamin D supplementation prevents fractures is not clear What this paper adds Four monthly oral supplementation with 100 000 IU vitamin D reduces fractures in men and women aged over 65 living in the general community  Total fracture incidence was reduced by 22 % and fractures in major osteoporotic sites by 33 CONTEXT Lower serum 25-hydroxyvitamin D concentrations are associated with greater risks of many chronic diseases across large , prospect i ve community-based studies . Substrate 25-hydroxyvitamin D must be converted to 1,25-dihydroxyvitamin D for full biological activity , and complex metabolic pathways suggest that interindividual variability in vitamin D metabolism may alter the clinical consequences of measured serum 25-hydroxyvitamin D. OBJECTIVE To investigate whether common variation within genes encoding the vitamin D-binding protein , megalin , cubilin , CYP27B1 , CYP24A1 , and the vitamin D receptor ( VDR ) modify associations of low 25-hydroxyvitamin D with major clinical outcomes . DESIGN , SETTING , AND PARTICIPANTS Examination of 141 single-nucleotide polymorphisms in a discovery cohort of 1514 white participants ( who were recruited from 4 US regions ) from the community-based Cardiovascular Health Study . Participants had serum 25-hydroxyvitamin D measurements in 1992 - 1993 and were followed up for a median of 11 years ( through 2006 ) . Replication meta-analyses were conducted across the independent , community-based US Health , Aging , and Body Composition ( n = 922 ; follow-up : 1998 - 1999 through 2005 ) , Italian Invecchiare in Chianti ( n = 835 ; follow-up : 1998 - 2000 through 2006 ) , and Swedish U 
    Output:
    
The meta- analysis suggests a moderate inverse association of 25(OH)D concentration with total cancer incidence and mortality