***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: Psoriasis is a genetically determined disease characterized by hyperproliferation and disordered maturation of the epidermis . Th1 lymphocytes are implicated in its pathogenesis . The vitamin D receptor ( VDR ) is a c and i date modifying gene , having immunosuppressive effects and being involved in anti-proliferative and pro-differentiation pathways in keratinocytes . There is suggestive evidence that the A allele of the A-1012 G polymorphism is associated with down-regulation of the Th1 response , via GATA-3 . The F and T alleles of Fok1 and Taq1 have been associated with increased VDR activity . The present study aim ed to test the hypothesis that the A allele of A-1012 G is protective for occurrence and severity of psoriasis and enhances therapeutic response to  vitamin D analogues and that these effects would be additive to those of Fok1 and Taq1 . The study group comprised 206 psoriasis patients who had received topical calcipotriol treatment and 80 controls .  There was no significant linkage disequilibrium between any pair of the three polymorphic sites ( P=0.3–0.8 ) . The A , F and T alleles were positively associated with calcipotriol response : AA genotype ( compared to AG/GG ) , odds ratio (OR)=2.18 ( P=0.04 ) ; TT , OR=1.97 ( P=0.03 ) ; AAFF genotype combination , OR=4.11 ( P=0.03 ) ; AATT , OR=5.64 ( P=0.005 ) ; and FFTT , OR=3.22 ( P=0.01 ) . Comparing patients without , to patients with , a family history of psoriasis , the A allele was under represented ( P=0.01 ) and the AAFF genotype combination even more so ( compared to residual genotypes ) ( OR=0.24 ; P=0.005 ) . AAFF was also under-represented in patients without a family history compared to controls ( OR=0.31 ; P=0.04 ) . There were no associations of family history with Fok1 and Taq1 . There were no associations of severity of psoriasis with any polymorphism . In conclusion , the A-1012 G , Fok1 and Taq1 VDR polymorphisms were associated with response to calcipotriol . A-1012 G and Fok1 were associated with susceptibility to non-familial psoriasis 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 % Calcitriol , via its receptor ( VDR ) is a main regulator of PTH secretion and parathyroid cell proliferation . Recently , marked overrepresentation of the polymorphic VDR alleles b , a , and T was found in patients with primary hyperparathyroidism ( pHPT ) , which suggests pathogenic importance in the disease . Using the ribonuclease protection assay , relative VDR and PTH messenger ribonucleic acid ( mRNA ) levels of parathyroid adenomas from 42 patients with sporadic pHPT were related to these VDR polymorphisms . The tumors of patients homozygous for the b , a , or T alleles demonstrated significantly lower VDR and higher PTH mRNA levels than those exhibiting the BB , AA , or tt genotypes ( P < 0.0001 - 0.02 ) , whereas heterozygotes had intermediate values . A similar discrepancy was found when comparing the baT and non-baT haplotypes ( 0.042 + /- 0.005 vs. 0.064 + /- 0.004 for VDR ; 34.4 + /- 3.7 vs. 21.6 + /- 2.2 for PTH ; both P < 0.005 ) . The lower VDR mRNA levels associated with the b , a , and T alleles may affect the calcitriol-mediated control of parathyroid function and thereby contribute to the development of sporadic pHPT 
    Output:
    
In conclusion , data summarized in this review support the concept that the vitamin D endocrine system ( VDES ) is of importance for pathogenesis and progression of MM and other types of skin cancer