You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Vitamin D receptor gene polymorphisms, particularly the novel A-1012G promoter polymorphism, are associated with vitamin D3 responsiveness and non-familial susceptibility in psoriasis
Abstract 1:
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


Title 2:
A novel polymorphism in the 1A promoter region of the vitamin D receptor is associated with altered susceptibilty and prognosis in malignant melanoma
Abstract 2:
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 %


Title 3:
Vitamin D receptor (VDR) and parathyroid hormone messenger ribonucleic acid levels correspond to polymorphic VDR alleles in human parathyroid tumors.
Abstract 3:
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
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