***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 There is clear evidence that nutrition and lifestyle can modify colorectal cancer risk . However , it is not clear if those factors can affect colorectal cancer treatment , recurrence , survival and quality of life . This paper describes the background and design of the “ COlorectal cancer : Longitudinal , Observational study on Nutritional and lifestyle factors that may influence colorectal tumour recurrence , survival and quality of life ” – COLON – study . The main aim of this study is to assess associations of diet and other lifestyle factors , with colorectal cancer recurrence , survival and quality of life . We extensively investigate diet and lifestyle of colorectal cancer patients at diagnosis and during the following years ; this design paper focusses on the initial exposures of interest : diet and dietary supplement use , body composition , nutrient status ( e.g. vitamin D ) , and composition of the gut microbiota . Methods / Design The COLON study is a multi-centre prospect i ve cohort study among at least 1,000 incident colorectal cancer patients recruited from 11 hospitals in the Netherl and s. Patients with colorectal cancer are invited upon diagnosis . Upon recruitment , after 6 months , 2 years and 5 years , patients fill out food-frequency question naires ; question naires about dietary supplement use , physical activity , weight , height , and quality of life ; and donate blood sample s. Diagnostic CT-scans are collected to assess cross-sectional areas of skeletal muscle , subcutaneous fat , visceral fat and intermuscular fat , and to assess muscle attenuation . Blood sample s are biobanked to facilitate future analyse of biomarkers , nutrients , DNA etc . Analysis of serum 25-hydroxy vitamin D levels , and analysis of metabolomic profiles are scheduled . A subgroup of patients with colon cancer is asked to provide faecal sample s before and at several time points after colon resection to study changes in gut microbiota during treatment . For all patients , information on vital status is retrieved by linkage with national registries . Information on clinical characteristics is gathered from linkage with the Netherl and s Cancer Registry and with hospital data bases . Hazards ratios will be calculated for dietary and lifestyle factors at diagnosis in relation to recurrence and survival . Repeated measures analyses will be performed to assess changes over time in dietary and other factors in relation to recurrence and survival We investigated the association between plasma 25(OH)D and the subsequent  colorectal cancer incidence risk by a nested case – control study in The Japan Public Health Center-based Prospect i ve Study , covering 375 newly diagnosed cases of colorectal cancer from 38 373 study subjects during a 11.5-year follow-up after blood collection . Two controls were matched per case on sex , age , study area , date of blood draw , and fasting time . In a conditional logistic regression model with matched pairs adjusted for smoking , alcohol consumption , body mass index , physical exercise , vitamin supplement use , and family history of colorectal cancer , plasma 25(OH)D was not significantly associated with colorectal cancer in men or in women . However , the lowest category of plasma 25(OH)D was associated with an elevated risk of rectal cancer in both men ( odds ratio ( OR ) , 4.6 ; 95 % confidence interval ( CI ) , 1.0–20 ) and women ( OR , 2.7 , 95 % CI , 0.94–7.6 ) , compared with the combined category of the other quartiles . Our results suggest that a low level of plasma 25(OH)D may increase the risk of rectal cancer Objective To examine the association between pre-diagnostic circulating vitamin D concentration ,  dietary intake of vitamin D and calcium  , and the  risk of colorectal cancer in European population s. Design Nested case-control study . Setting The study was conducted within the EPIC study , a cohort of more than 520 000 participants from 10 western European countries . Participants 1248 cases of incident colorectal cancer , which developed after enrolment into the cohort , were matched to 1248 controls Main outcome measures Circulating vitamin D concentration ( 25-hydroxy-vitamin-D , 25-(OH)D ) was measured by enzyme immunoassay . Dietary and lifestyle data were obtained from question naires . Incidence rate ratios and 95 % confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models , with adjustment for potential dietary and other confounders . Results 25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer ( P for trend < 0.001 ) . Compared with a pre-defined mid-level concentration of 25-(OH)D ( 50.0 - 75.0 nmol/l ) , lower levels were associated with higher colorectal cancer risk ( < 25.0 nmol/l : incidence rate ratio 1.32 ( 95 % confidence interval 0.87 to 2.01 ) ; 25.0 - 49.9 nmol/l : 1.28 ( 1.05 to 1.56 ) , and higher concentrations associated with lower risk ( 75.0 - 99.9 nmol/l : 0.88 ( 0.68 to 1.13 ) ; ≥100.0 nmol/l : 0.77 ( 0.56 to 1.06 ) ) . In analyses by quintile of 25-(OH)D concentration , patients in the highest quintile had a 40 % lower risk of colorectal cancer than did those in the lowest quintile ( P<0.001 ) . Subgroup analyses showed a strong association for colon but not rectal cancer ( P for heterogeneity=0.048 ) .  Greater dietary intake of calcium  was associated with a lower colorectal cancer risk . Dietary vitamin D  was not associated with disease risk . Findings did not vary by sex and were not altered by corrections for season or month of blood donation . Conclusions The results of this large observational study indicate a strong inverse association between levels of pre-diagnostic 25-(OH)D concentration and  risk of colorectal cancer in western European population s. Further r and omised trials are needed to assess whether increases in circulating 25-(OH)D concentration can effectively decrease the risk of colorectal cancer Abstract Objective To evaluate the association between pre-diagnostic circulating vitamin D concentration and the subsequent risk of overall and site specific cancer in a large cohort study . Design Nested case-cohort study within the Japan Public Health Center-based Prospect i ve Study cohort . Setting Nine public health centre areas across Japan . Participants 3301 incident cases of cancer and 4044 r and omly selected subcohort participants .  Exposure Plasma concentration of 25-hydroxyvitamin D measured by enzyme immunoassay . Participants were divided into quarters based on the sex and season specific distribution of 25-hydroxyvitamin D among subcohorts . Weighted Cox proportional hazard models were used to calculate the multivariable adjusted hazard ratios for overall and site specific cancer across categories of 25-hydroxyvitamin D concentration , with the lowest quarter as the reference . Main outcome measure Incidence of overall or site specific cancer . Results Plasma 25-hydroxyvitamin D concentration was inversely associated with the risk of total cancer , with multivariable adjusted hazard ratios for the second to fourth quarters compared with the lowest quarter of 0.81 ( 95 % confidence interval 0.70 to 0.94 ) , 0.75 ( 0.65 to 0.87 ) , and 0.78 ( 0.67 to 0.91 ) , respectively ( P for trend=0.001 ) . Among the findings for cancers at specific sites , an inverse association was found for liver cancer , with corresponding hazard ratios of 0.70 ( 0.44 to 1.13 ) , 0.65 ( 0.40 to 1.06 ) , and 0.45 ( 0.26 to 0.79 ) ( P for trend=0.006 ) . A sensitivity analysis showed that alternately removing cases of cancer at one specific site from total cancer cases did not substantially change the overall hazard ratios . Conclusions In this large prospect i ve study , higher vitamin D concentration was associated with lower risk of total cancer . These findings support the hypothesis that vitamin D has protective effects against cancers at many sites 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 Calcium and vitamin D both appear to have antineoplastic effects in the large bowel . Although these nutrients are inter-related metabolically in bone and in the normal intestine , their potential interactions in large-bowel carcinogenesis are not well understood . METHODS We assessed independent and joint effects of calcium supplementation and vitamin D status on  adenoma recurrence in 803 subjects in a multi-center , placebo-controlled r and omized clinical trial of calcium supplementation for the prevention of colorectal adenoma recurrence . Serum levels of 25-hydroxy [ 25-(OH ) ] vitamin D and 1,25-dihydroxy [ 1,25-(OH)2 ] vitamin D levels were determined , and the Taq I and Fok I polymorphisms in the vitamin D receptor ( VDR ) gene were analyzed by polymerase chain reaction . Risk ratios ( RRs ) for any adenoma recurrence were computed for calcium supplementation within groups defined by serum vitamin D levels and for serum vitamin D levels within treatment groups . Associations of VDR polymorphisms with recurrence risk were also evaluated . All statistical tests were two-sided . RESULTS Among subjects with baseline 25-(OH ) vitamin D levels at or below the median ( 29.1 ng/mL ) , calcium supplementation was not associated with adenoma recurrence , whereas among those with levels above the median , calcium supplementation was associated with a reduced risk ( RR = 0.71 , 95 % confidence interval [ CI ] = 0.57 to 0.89 , P for interaction = .012 ) . Conversely , serum 25-(OH ) vitamin D levels were associated with a reduced risk only among subjects receiving calcium supplements ( RR per 12 ng/mL increase of vitamin D = 0.88 , 95 % CI = 0.77 to 0.99 , P for interaction = .006 ) . VDR polymorphisms were not related to adenoma recurrence and did not modify the associations with vitamin D or calcium . CONCLUSIONS Calcium supplementation and vitamin D status appear to act largely together , not separately , to reduce the risk of colorectal adenoma recurrence . VDR genotype does not appear to be associated with risk 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 . INTER 
    Output:
    
Conclusions The results of this meta‐ analysis indicate that blood circulating vitamin D level is associated with decreased risk of colorectal cancer in Asian countries .
The dose-response meta- analysis shows that the strength of this association among the Asian population is similar to that among the Western population .
Our study suggests that the Asian population should improve nutritional status and maintain a higher level of blood circulating vitamin