***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: Genetic variation in vitamin D – related genes has not been investigated comprehensively and findings are equivocal . We studied the association between polymorphisms across the entire vitamin D receptor ( VDR ) gene and genes encoding for vitamin D activating enzyme 1-α-hydroxylase ( CYP27B1 ) and deactivating enzyme 24-hyroxylase ( CYP24A1 ) and prostate cancer risk among middle-aged men using a population -based case-control study design . DNA sample s and survey data were obtained from incident cases ( n = 630 ) , 40 to 64 years old , identified through the Seattle-Puget Sound Surveillance , Epidemiology , and End Results cancer registry from 1993 to 1996 and from r and om controls ( n = 565 ) of similar age without a history of prostate cancer . We selected and genotyped tag single-nucleotide polymorphisms to predict common variants across VDR ( n = 22 ) , CYP27B1 ( n = 2 ) , and CYP24A1 ( n = 14 ) . Haplotypes of VDR and CYP24A1 were not associated with prostate cancer risk . In the genotype analysis , homozygotes at two VDR loci ( rs2107301 and rs2238135 ) were associated with a 2- to 2.5-fold higher risk of prostate cancer compared with the homozygote common allele [ odds ratio , 2.47 ( 95 % confidence interval , 1.52 - 4.00 ; P = 0.002 ) and 1.95 ( 95 % confidence interval , 1.17 - 3.26 ; P = 0.007 ) , respectively ; P value corrected for multiple comparisons for VDR = 0.002 ] . We found no evidence that the two associated VDR single-nucleotide polymorphisms were modified by age at diagnosis , prostate cancer aggressiveness , first-degree family history of prostate cancer , or vitamin D intake . Genotypes of CYP27B1 and CYP24A1 were not associated with prostate cancer risk . Our findings suggest that polymorphisms in the VDR gene may be associated with prostate cancer risk and , therefore , that the vitamin D pathway might have an etiologic role in the development of prostate cancer . ( Cancer Epidemiol Biomarkers Prev 2007;16(10):1990–9 Introduction The involvement of vitamin D receptor ( VDR ) , which is a key mediator in the vitamin D pathway , in breast cancer etiology has long been of interest . Methods We examined the association between polymorphisms in the 3 ' end of the VDR gene , specifically BsmI and Poly(A ) , and breast cancer risk within a large , population -based , case-control study of breast cancer . Cases ( n = 1,631 ) were Caucasian and African-American women , aged 35 to 64 years , who were diagnosed with incident , invasive breast cancer between July 1994 and April 1998 . Control individuals ( n = 1,435 ) were women without breast cancer ascertained through r and om digit dialing .  Results Accounting for age , study site , and sampling weights , we observed a significantly increased risk for breast cancer among Caucasian , postmenopausal carriers of the bb genotype of BsmI ( odds ratio = 1.53 , 95 % confidence interval = 1.04 to 2.27 ) . However , no associations with the bb genotype were observed in African-American women . Overall , there were no significant associations between the Poly(A ) genotype and breast cancer risk in either racial group . Smoking status ( ever/never ) modified the association between both the BsmI and Poly(A ) genotypes and breast cancer risk . The respective associations between these genotypes and breast cancer risk did not significantly vary by oral contraceptive use , hormone replacement therapy , or body mass index . Conclusion Our results provide additional support for an increased risk for breast cancer  in postmenopausal Caucasian women with the BsmI bb genotype and shed light on possible differential effects by menopausal status and race PURPOSE Substantial experimental and epidemiological data indicate that 1,25-dihydroxyvitamin D3 ( calcitriol ) has potent antiproliferative effects on human prostate cancer cells . We performed an open label , nonr and omized pilot trial to determine whether calcitriol therapy is safe and efficacious for early recurrent prostate cancer . Our hypothesis was that calcitriol therapy slows the rate of rise of prostate specific antigen ( PSA ) compared with the pretreatment rate . MATERIAL S AND METHODS After primary treatment with radiation or surgery recurrence was indicated by rising serum PSA levels documented on at least 3 occasions . Seven subjects completed 6 to 15 months of calcitriol therapy , starting with 0.5 microg . calcitriol daily and slowly increasing to a maximum dose of 2.5 microg . daily depending on individual calciuric and calcemic responses . Each subject served as his own control , comparing the rate of PSA rise before and after calcitriol treatment . RESULTS As determined by multiple regression analysis , the rate of PSA rise during versus before calcitriol therapy significantly decreased in 6 of 7 patients , while in the remaining man a deceleration in the rate of PSA rise did not reach statistical significance . Overall the decreased rate of PSA rise was statistically significant ( p = 0.02 Wilcoxon signed rank test ) . Dose dependent hypercalciuria limited the maximal calcitriol therapy given ( range 1.5 to 2.5 microg . daily ) . CONCLUSIONS This pilot study provides preliminary evidence that calcitriol effectively slows the rate of PSA rise in select cases , although dose dependent calciuric side effects limit its clinical usefulness . The development of calcitriol analogues with decreased calcemic side effects is promising , since such analogues may be even more effective for treating prostate cancer The association of Taq 1 and Fok 1 restriction fragment length polymorphisms of the vitamin D receptor with occurrence and outcome of malignant melanoma ( MM ) , as predicted by tumour ( Breslow ) thickness , has been reported previously . We now report a novel adenine – guanine substitution −1012 bp relative to the exon 1a transcription start site ( A-1012 G ) , found following screening by single-str and ed conformational polymorphism of this promoter region . There was a total of 191 MM cases , which were stratified according to conventional Breslow thickness groups , cases being r and omly selected from each group to form a distribution corresponding to the known distribution of Breslow thickness in our area , and this population ( n=176 ) was compared to 80 controls . The A allele was over-represented in MM patients and , with GG as reference , odds ratio ( OR ) for AG was 2.5 , 95 % confidence interval ( CI ) 1.1–5.7 , ( P=0.03 ) and AA 3.3 , CI 1.4–8.1 , ( P=0.007 ) . The outcome was known in 171 of 191 patients and the A allele was related to the development of metastasis , the Kaplan – Meier estimates of the probability of metastasis at 5 years being : GG 0 % ; AG 9 % , CI 4–16 % ; AA 21 % , CI 12–36 % ; ( P=0.008 ) , and to thicker Breslow thickness groups ( P=0.04 ) . The effect on metastasis was independent of tumour thickness and A-1012 G may have predictive potential , additional to Breslow thickness . Neither the Fok 1 nor Taq 1 variants ( f and t ) were significantly related to the development of metastasis , although there was a strong relationship of fftt with the thickest Breslow thickness group ( P=0.005 ) . There was an interaction between the A-1012 G and Fok 1 polymorphisms ( P=0.025 ) and the Fok 1 variant enhanced the effect of the A allele of the A-1012 G polymorphism on metastasis , the probability of metastasis for AAff at 5 years follow-up being 57 % , CI 24–92 % We examined whether selected polymorphisms in 11 c and i date genes and serum levels of insulin-like growth factor I ( IGF-I ) help predict the presence of prostate cancer among patients prescreened with prostate-specific antigen ( PSA ) and digital rectal exam ( DRE ) .  We studied 1031 consecutive men who underwent one or more prostate biopsies because of an elevated PSA level ( > 4 ng/ml ) or an abnormal DRE . Eleven c and i date genes were examined , including the and rogen receptor , SRD5A2 , CYP17 , CYP3A4 , vitamin D receptor , PSA , GST-T1 , GST-M1 , GST-P1 , IGF-I , and IGF binding protein 3 . We also measured serum IGF-I levels before biopsy . Of the 1031 men , 483 had cancer on any biopsy ( cases ) and 548 men had no cancer ( controls ) . Age , ethnicity , total PSA , and DRE result were strongly predictive of the presence of prostate cancer . The mean IGF-I level for cases ( 119.4 ng/ml ) was lower than for controls ( 124.4 ng/ml , P = 0.05 ) and were not predictive for the presence of prostate cancer . We found no associations between the and rogen receptor , SRD5A2 , CYP17 , CYP3A4 , vitamin D receptor , GST-M1 , GST-P1 , and IGF binding protein 3 genotypes and prostate cancer risk . The adjusted odds ratios for having prostate cancer for patients with the GST-T1 and IGF-I variant alleles were 1.64 ( 95 % confidence interval , 1.1 - 2.4 ; P = 0.01 ) and 1.70 ( 95 % confidence interval , 1.1 - 2.7 ; P = 0.02 ) , respectively . Nine of 11 c and i date genes were not significantly predictive for prostate cancer in a clinical setting . The GST-T1 and IGF-I polymorphisms demonstrated modest associations with prostate cancer risk . IGF-I levels were not helpful in identifying patients with prostate cancer at the time of biopsy Operating through the vitamin D receptor ( VDR ) , vitamin D inhibits prostate cancer growth and increases insulin-like growth factor binding protein ( IGFBP ) expression , suggesting that the vitamin D and insulin-like growth factor ( IGF ) regulatory systems may operate together to affect prostate cancer . Among 191 newly diagnosed prostate cancer cases and 304 r and omly selected population controls in Shanghai , China , we found no significant association between the BsmI or FokI VDR gene polymorphisms and prostate cancer risk . However , we found that among men with the ff FokI genotype , those in the highest tertile of plasma IGFBP-3 had a decreased risk versus those in the lowest tertile ( odds ratio , 0.14 ; 95 % confidence interval , 0.04 - 0.56 ; P(trend ) < 0.01 ) , whereas among men with the FF and Ff genotypes , IGFBP-3 was not associated with risk . Similarly , IGFBP-1 was inversely associated with prostate cancer risk only among men with the ff FokI genotype ( odds ratio , 0.25 ; 95 % confidence interval , 0.07 - 0.85 ; P(trend ) = 0.02 ) . No such FokI genotype-specific effects were observed for IGF-I or IGF-II . Our findings in a low-risk population suggest that the IGF and vitamin D regulatory systems may interact to affect prostate cancer risk . Larger studies are needed to confirm these findings and clarify the underlying mechanisms Laboratory studies and epidemiological investigations suggest that vitamin D plays a role in the etiology of colorectal adenomas , possibly through a mechanism mediated by the vitamin D receptor ( VDR ) . We conducted a clinic-based case-control study to examine the association between VDR polymorphisms and  colorectal adenomas .  We selectively identified a r and om subset of 393 cases of colorectal adenomas and 406 colonoscopy-negative controls from a clinic-based case-control study conducted in the metropolitan Minneapolis/St . Paul area during 1991 - 1994 . A self-administered question naire was used to collect data on dietary and supplement intake of vitamin D and calcium , as well as on demographics , physical activity , medical information , lifestyle factors , reproductive history , and anthropometry . DNA was extracted from whole blood and assayed for the BsmI VDR polymorphism using an ABI 7700 TaqMan assay .  Adjusted odds ratios ( OR ) and 95 % confidence intervals ( CIs ) were evaluated using logistic regression . Compared with the bb genotype ( 33 % of controls ) , neither the Bb ( 48.8 % of controls ) nor the BB ( 18.2 % of controls ) genotypes was strongly associated with risk of colorectal adenomas ( OR = 0.86 , CI = 0.63 - 1.19 and OR = 0.77 , CI = 0.50 - 1.18 , respectively ) . However , those with the lowest tertile of vitamin D intake and the BB genotype had a lower risk of colorectal adenoma ( OR = 0.24 , CI = 0.08 - 0.76 ) than those with the highest tertile of intake and the b 
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Obviously , at present it is still not possible to make any definitive statements about the importance of the VDR genotype for cancer occurrence .
Moreover , it is often noticed that the same VDR polymorphism has a different effect depending on the type of cancer , or may be only decisive for more or less aggressive staging of the tumour .
After careful evaluation of the actual literature , it can be summarized that data indicating an association of VDR polymorphisms and cancer risk are strongest for breast cancer ( Bsm1 , Fok1 ) , prostate cancer ( Fok1 ) and malignant melanoma ( MM ) ( Fok1 ) .
Data indicating an association of VDR polymorphisms and cancer prognosis are strongest for prostate cancer ( Fok1 ) , breast cancer ( Bsm1 , Taq1 ) , MM ( Bsm1 ) and renal cell carcinoma ( Taq1 )