***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 : Vitamin D , from diet and sunlight exposure , may be associated with reduced breast-cancer risk . This study investigated if c and i date gene variants in vitamin D pathways are associated with breast cancer risk , or modify the associations between breast cancer and vitamin D exposure . Methods : Breast cancer cases aged 25 to 74 years were identified from the Ontario Cancer Registry ( histopathologically confirmed and diagnosed 2002–2003 ) and population -based controls were identified through r and om digit dialing of Ontario households .  Saliva ( DNA ) was available for 1,777 cases and 1,839 controls .  Multivariate logistic regression was used to evaluate associations between 19 single nucleotide polymorphisms ( SNP ) in vitamin D related genes , including vitamin D binding protein ( GC ) , vitamin D receptor ( VDR ) , and cytochrome P450 type 24A1 ( CYP24A1 ) . Statistical interactions were assessed using the likelihood ratio test . Results : Some SNPs were found to be significantly associated with breast cancer risk . For example , breast cancer risk was associated with the GC rs7041 TT genotype ( age-adjusted odds ratio ( OR ) = 1.23 ; 95 % CI : 1.01 , 1.51 ) and inversely with the VDR Fok1 ( rs2228570 ) ff genotype ( OR = 0.71 ; 95 % CI : 0.57 , 0.88 ) . Few significant gene-environment interactions were observed between dietary vitamin D and genetic variants . Conclusion : Our study suggests certain vitamin D related genetic variants may influence breast-cancer risk and we found limited evidence that genetic variants modify the associations between vitamin D exposure and breast cancer risk . Impact : Variation in vitamin D-related genotypes may help to explain inconsistent results from previous epidemiologic studies and may lead to targeted prevention strategies . Cancer Epidemiol Biomarkers Prev ; 20(8 ) ; 1708–17 . © 2011 AACR Background Higher sunlight exposure is correlated with lower incidence of breast cancer in ecological studies , but findings from prospect i ve studies regarding the association of circulating levels of vitamin D with the risk of breast cancer have been null . The objective of this study was to examine the relation between plasma levels of vitamin D  and the risk of postmenopausal breast cancer . Methods We conducted a nested case – control study within the Multiethnic Cohort Study of five race/ethnic groups ( white , African-American , Native Hawaiian , Japanese , and Latino ) from Hawaii and Los Angeles between 2001 and 2006 . Pre-diagnostic plasma levels of 25-hydroxyvitamin D2 [ 25(OH)D2 ] , 25-hydroxyvitamin D3 [ 25(OH)D3 ] and 25(OH)D ( sum of 25(OH)D2 and 25(OH)D3 )  were examined among 707 postmenopausal breast cancer cases and matched controls . Results Using conditional logistic regression models , 20 ng/mL increases of plasma 25(OH)D3 ( odds ratio ( OR ) 0.28 ; 95 % confidence interval ( CI ) 0.14 - 0.56 ) and 25(OH)D ( OR 0.43 ; 95 % CI 0.23 - 0.80 ) were inversely associated with breast cancer risk among white women , but not among women in other race/ethnic groups . Using two-segmented , piecewise-linear logistic regression models , the change-points of the ORs , either for 25(OH)D3 or for 25(OH)D , were detected as 20 ng/mL among whites . Conclusions Circulating 25(OH)D3 and 25(OH)D were associated with a reduced risk of  postmenopausal breast cancer among whites , but not in other ethnic groups , who reside in low latitude regions Background : Calcium , vitamin D , and dairy products are highly correlated factors , each with potential roles in breast carcinogenesis . Few prospect i ve studies have examined these relationships in postmenopausal women . Methods : Participants in the Cancer Prevention Study II Nutrition Cohort completed a detailed question naire on diet , vitamin and mineral supplement use , medical history , and lifestyle in 1992 to 1993 . After exclusion of women with a history of cancer and incomplete dietary data , 68,567 postmenopausal women remained for analysis . During follow-up through August 31 , 2001 , we identified 2,855 incident cases of breast cancer . Multivariate-adjusted rate ratios ( RR ) were calculated using Cox proportional hazards models . Results : Women with the highest intake of dietary calcium ( > 1,250 mg/d ) were at a lower risk of breast cancer than those reporting ≤500 mg/d [ RR , 0.80 ; 95 % confidence interval ( 95 % CI ) , 0.67 - 0.95 ; Ptrend = 0.02 ] ; however , neither use of supplemental calcium nor vitamin D intake was associated with risk . Consumption starting at two or more servings of dairy products per day was likewise inversely associated with risk ( RR , 0.81 ; 95 % CI , 0.69 - 0.95 ; Ptrend = 0.002 , compared with < 0.5 servings/d ) . The associations were slightly stronger in women with estrogen receptor – positive tumors comparing highest to lowest intake : dietary calcium  ( RR , 0.67 ; 95 % CI , 0.51 - 0.88 ; Ptrend = 0.004 ) ; dairy products ( RR , 0.73 ; 95 % CI , 0.57 - 0.93 ; Ptrend = 0.0003 ) , and dietary vitamin D ( RR , 0.74 ; 95 % CI , 0.59 - 0.93 ; Ptrend = 0.006 ) . Conclusions : Our results support the hypothesis that dietary calcium and /or some other components in dairy products may modestly reduce risk of postmenopausal breast cancer . The stronger inverse associations among estrogen receptor – positive tumors deserve further study . ( Cancer Epidemiol Biomarkers Prev 2005;14(12):2898–904 Purpose Prior prospect i ve studies , including our own , have evaluated total plasma 25-hydroxyvitamin D [ 25(OH)D ] and breast cancer risk with inconsistent results . However , recent studies suggest that some vitamin D functions may be more relevant to the unbound ( free ) fraction of 25(OH)D. Vitamin D binding protein ( DBP ) influences the free 25(OH)D levels and thus possibly the biological activities of vitamin D. Methods We conducted a case – control study nested within the Nurses ’ Health Study II to evaluate the association of plasma free 25(OH)D and DBP with breast cancer risk in predominantly premenopausal women .  Plasma sample s were assayed for 25(OH)D and DBP in 584 case – control pairs .  Free 25(OH)D levels were calculated based on plasma levels of total 25(OH)D , DBP , and a constant value representing average albumin levels . Conditional logistic regression was used to estimate relative risks ( RRs ) and 95 % confidence intervals ( CIs ) . Results We found no association between plasma calculated free 25(OH)D and risk of breast cancer overall ( highest vs. lowest quartile RR 1.21 , 95 % CI 0.83–1.77 , trend test p value = 0.50 ) . No association was observed for plasma DBP as well ( highest vs. lowest quartile RR 0.95 , 95 % CI 0.67–1.36 , trend test p value = 0.96 ) . Results were similar by tumor hormone receptor status . Neither the total nor the calculated free 25(OH)D and breast cancer association substantially varied by plasma DBP levels . Conclusions Our study does not support an important role of either calculated circulating free 25(OH)D or circulating DBP levels in breast cancer risk among predominantly premenopausal women Several lines of evidence suggest that vitamin D may reduce incidence of breast cancer , but few epidemiologic studies have addressed the relation of plasma vitamin D metabolites to the risk of this disease . We prospect ively examined the relationship between plasma levels of 25-hydroxyvitamin D [ 25(OH)D ] and 1,25-dihydroxyvitamin D [ 1,25(OH)2D ] and  risk of breast cancer  in a case-control study nested within the Nurses ' Health Study cohort .  Blood sample s were collected from study participants in 1989 - 1990 . Breast cancer cases developing between blood collection and June 1 , 1996 , were matched to cancer-free controls on the basis of age , menopausal status , and other factors . Stored plasma sample s from 701 cases and 724 controls were available for metabolite analysis . Cases had a lower mean 25(OH)D level than controls ( P = 0.01 ) , but mean 1,25(OH)2D levels were similar ( P = 0.49 ) . High levels of both metabolites were associated with a nonsignificant lower risk of breast cancer . Women in the highest quintile of 25(OH)D had a relative risk of 0.73 ( 95 % confidence interval = 0.49 - 1.07 ; Ptrend = 0.06 ) compared with those in the lowest quintile . For 1,25(OH)2D , the comparable relative risk was 0.76 ( 95 % confidence interval = 0.52 - 1.11 ; Ptrend = 0.39 ) . For both metabolites , the association was stronger in women ages 60 years and older , but results were not statistically significant . Our findings suggest that high levels of 25(OH)D , and perhaps 1,25(OH)2D , may be modestly associated with reduced risk of breast cancer Introduction Experimental evidence indicates vitamin D may play an important role in breast cancer etiology but epidemiologic evidence to date is inconsistent . Vitamin D comes from dietary intake and sun exposure and plasma levels of 25-hydroxyvitamin D ( 25(OH)D ) are considered the best measure of vitamin D status . Methods We conducted a prospect i ve nested case-control study within the Nurses ' Health Study II ( NHSII ) . Plasma sample s collected in 1996 to 1999 were assayed for 25(OH)D  in 613 cases , diagnosed after blood collection and before 1 June 2007 , and in 1,218 matched controls .  Multivariate relative risks ( RR ) and 95 % confidence intervals ( CI ) were calculated by conditional logistic regression , adjusting for several breast cancer risk factors . Results No significant association was observed between plasma 25(OH)D levels and breast cancer risk ( top vs. bottom quartile multivariate RR = 1.20 , 95 % CI ( 0.88 to 1.63 ) , P-value , test for trend = 0.32 ) . Results were similar when season-specific quartile cut points were used . Results did not change when restricted to women who were premenopausal at blood collection or premenopausal at diagnosis . Results were similar between estrogen receptor (ER)+/progesterone receptor (PR)+ and ER-/PR- tumors ( P-value , test for heterogeneity = 0.51 ) . The association did not vary by age at blood collection or season of blood collection , but did vary when stratified by body mass index ( P-value , test for heterogeneity = 0.01 ) . Conclusions Circulating 25(OH)D levels were not significantly associated with breast cancer risk in this predominantly premenopausal population Background Early life exposures , including diet , have been implicated in the etiology of breast cancer . Methods A nested case-control study was conducted among participants in the Nurses ' Health Study who completed a 24-item question naire about diet during high school .  There were 843 eligible cases diagnosed between onset of study ( 1976 ) and before the return of the high school diet question naire ( 1986 ) , who were matched 10:1 with controls on the basis of age . Results Women who had , during adolescence , a higher consumption of eggs , vegetable fat and fiber  had a lower risk of breast cancer , whereas risk of breast cancer was increased among women who consumed more butter . Conclusions A possible association of elements of adolescent diet with risk of breast cancer is reported , but the findings require confirmation in prospect i ve study Background Vitamin D deficiency , which has been linked to an increased risk of colorectal cancer , is particularly common among African Americans . Previous studies of vitamin D status and breast cancer risk , mostly conducted in white women , have had conflicting results . We examined the relationship between predicted  vitamin D status and incidence of breast cancer in a cohort of 59,000 African American women . Methods Participants in the Black Women ’s Health Study have been followed by biennial mail question naires since 1995 , with self-reported diagnoses of cancer confirmed by hospital and cancer registry records . Repeated five-fold cross-validation with linear regression was used to derive the best 25-hydroxyvitamin D ( 25(OH)D ) prediction model based on measured 25(OH)D in plasma specimens obtained from 2856 participants in 2013–2015 and question naire-based variables from the same time frame . In the full cohort , including 1454 cases of incident invasive breast cancer , Cox proportional ha 
    Output:
    
Conclusion : This systematic review suggests a protective relationship between circulating  vitamin D  ( measured as 25(OH ) D ) and breast cancer development in premenopausal women