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author:("Peris, petty")
1.  On the Interplay of Telomeres, Nevi and the Risk of Melanoma 
PLoS ONE  2012;7(12):e52466.
The relationship between telomeres, nevi and melanoma is complex. Shorter telomeres have been found to be associated with many cancers and with number of nevi, a known risk factor for melanoma. However, shorter telomeres have also been found to decrease melanoma risk. We performed a systematic analysis of telomere-related genes and tagSNPs within these genes, in relation to the risk of melanoma, dysplastic nevi, and nevus count combining data from four studies conducted in Italy. In addition, we examined whether telomere length measured in peripheral blood leukocytes is related to the risk of melanoma, dysplastic nevi, number of nevi, or telomere-related SNPs. A total of 796 cases and 770 controls were genotyped for 517 SNPs in 39 telomere-related genes genotyped with a custom-made array. Replication of the top SNPs was conducted in two American populations consisting of 488 subjects from 53 melanoma-prone families and 1,086 cases and 1,024 controls from a case-control study. We estimated odds ratios for associations with SNPs and combined SNP P-values to compute gene region-specific, functional group-specific, and overall P-value using an adaptive rank-truncated product algorithm. In the Mediterranean population, we found suggestive evidence that RECQL4, a gene involved in genome stability, RTEL1, a gene regulating telomere elongation, and TERF2, a gene implicated in the protection of telomeres, were associated with melanoma, the presence of dysplastic nevi and number of nevi, respectively. However, these associations were not found in the American samples, suggesting variable melanoma susceptibility for these genes across populations or chance findings in our discovery sample. Larger studies across different populations are necessary to clarify these associations.
doi:10.1371/journal.pone.0052466
PMCID: PMC3531488  PMID: 23300679
2.  MC1R variants predisposing to concomitant primary cutaneous melanoma in a monozygotic twin pair 
BMC Medical Genetics  2012;13:81.
Background
Concomitant primary cutaneous melanoma in monozygotic twins has been reported in only two pairs but in neither of them genetic analysis was performed. Two high-penetrance susceptibility genes, CDKN2A and CDK4 and one low-penetrance gene, MC1R, are well-defined genetic risk factors for melanoma. MITF has been recently identified as a novel intermediate risk melanoma-predisposing gene.
Case presentation
We describe the extraordinary occurrence of a primary cutaneous invasive melanoma in two 44-year-old identical, female twins, on the same body site within 30 days of each other and report for the first time the genetic analysis of melanoma susceptibility genes in both twins. Data on characteristics of the twins were collected through a standardized questionnaire and skin examination. Exons 1α, 1β, 2 and 3 of CDKN2A, exon 2 of CDK4, the entire open reading frame of MC1R and the recently described MITF c.952 G > A (p.Glu318Lys) variant were investigated by direct sequencing. Sequencing analysis of the high-penetrance susceptibility genes showed no changes in CDKN2A and in exon 2 of the CDK4 gene. Both patients were heterozygous for the same CDKN2A UTR c.*29C > G variant. Interestingly, the same two heterozygous variants of the MC1R were identified in both twins: the c.451C > T (p.Arg151Cys) and the c.456C > A (p.Tyr152*) variants. Neither patient showed the c.952 G > A (p.Glu318Lys) substitution in the MITF gene.
Conclusions
Identification of two high-risk MC1R variants in our identical twins in the absence of CDKN2A and CDK4 mutations highlights the contribution of low penetrance genes, such as MC1R, in melanoma susceptibility.
doi:10.1186/1471-2350-13-81
PMCID: PMC3483249  PMID: 22978401
Melanoma; Monozygotic twins; CDKN2A; CDK4; MC1R; MITF; Genetic susceptibility
3.  The IL23R R381Q Gene Variant Protects against Immune-Mediated Diseases by Impairing IL-23-Induced Th17 Effector Response in Humans 
PLoS ONE  2011;6(2):e17160.
IL-23 and Th17 cells are key players in tissue immunosurveillance and are implicated in human immune-mediated diseases. Genome-wide association studies have shown that the IL23R R381Q gene variant protects against psoriasis, Crohn's disease and ankylosing spondylitis. We investigated the immunological consequences of the protective IL23R R381Q gene variant in healthy donors. The IL23R R381Q gene variant had no major effect on Th17 cell differentiation as the frequency of circulating Th17 cells was similar in carriers of the IL23R protective (A) and common (G) allele. Accordingly, Th17 cells generated from A and G donors produced similar amounts of Th17 cytokines. However, IL-23-mediated Th17 cell effector function was impaired, as Th17 cells from A allele carriers had significantly reduced IL-23-induced IL-17A production and STAT3 phosphorylation compared to G allele carriers. Our functional analysis of a human disease-associated gene variant demonstrates that IL23R R381Q exerts its protective effects through selective attenuation of IL-23-induced Th17 cell effector function without interfering with Th17 differentiation, and highlights its importance in the protection against IL-23-induced tissue pathologies.
doi:10.1371/journal.pone.0017160
PMCID: PMC3043090  PMID: 21364948
4.  MC1R Variants Increase Risk of Melanomas Harboring BRAF Mutations 
Melanocortin-1 receptor (MC1R) variants have been associated with BRAF (v-raf murine sarcoma viral oncogene homolog B1) mutations in non-CSD (chronic solar-damaged) melanomas in an Italian and an American population. We studied an independent Italian population of 330 subjects (165 melanoma patients and 165 controls) to verify and estimate the magnitude of this association and to explore possible effect modifiers. We sequenced MC1R in all subjects and exon 15 of BRAF in 92/165 melanoma patients. Patients with MC1R variants had a high risk of carrying BRAF mutations in melanomas (odds ratio (OR) = 7.0, 95% confidence interval (CI) = 2.1–23.8) that increased with the number of MC1R variants and variants associated with red hair color. Combining these subjects with the originally reported Italian population (513 subjects overall), MC1R variant carriers had a 5- to 15-fold increased risk of BRAF-mutant melanomas based on carrying one or two variants (P<0.0001, test for trend), and regardless of signs of chronic solar damage. In contrast, no association with BRAF-negative melanomas was found (OR = 1.0, 95% CI = 0.6–1.6). No characteristics of subjects or melanomas, including age, nevus count, pigmentation, and melanoma thickness or location on chronically or intermittently sun-exposed body sites, substantially modified this association, although results could be affected by the small numbers in some categories. This study confirms that the known MC1R–melanoma risk association is confined to subjects whose melanomas harbor BRAF mutations.
doi:10.1038/jid.2008.67
PMCID: PMC2835495  PMID: 18368129
5.  A cost–utility analysis of etanercept for the treatment of moderate-to-severe psoriasis in Italy 
Introduction:
Biologic therapies have proven efficacious for patients with moderate-to-severe psoriasis. However, their economic value compared with standard of care in Italy has not been explored. This study estimates the cost-effectiveness of intermittent therapy with etanercept in patients with moderate-to-severe plaque-type psoriasis in comparison with nonsystemic therapy in Italy.
Methods:
This study employs cost–utility analysis using a Markov model adapted from the British “York model”. It compares the cost per quality-adjusted life-year (QALY) of intermittent etanercept (25 mg twice weekly) versus nonsystemic therapy. Data on efficacy and changes in quality of life were derived from three etanercept clinical trials. Direct costs of treating psoriasis patients, including hospitalizations and dermatology clinic visits, were taken from an Italian cost-of-illness study. Extrapolations were made to evaluate the cost-effectiveness of intermittent etanercept versus nonsystemic therapy over a period of ten years.
Results:
For the group of patients with moderate and severe plaque psoriasis (initial Psoriasis Area and Severity Index [PASI ≥ 10]) the incremental cost-effectiveness ratio (ICER) for etanercept compared with nonsystemic therapy was €33,216/QALY; for the group of patients with severe psoriasis (PASI ≥ 20), the ICER was €25,486/QALY.
Conclusions:
Within the Italian health care system, intermittent etanercept is a cost-effective therapeutic option compared with nonsystemic therapy for the group of patients with moderate and severe plaque psoriasis. For patients with PASI ≥ 20, cost-effectiveness of etanercept is even greater.
PMCID: PMC3169985  PMID: 21935307
cost-utility; cost-effectiveness; psoriasis; etanercept; Markov model
6.  Pruritic, serpiginous eruption in a returning traveller 
doi:10.1503/cmaj.080078
PMCID: PMC2464475  PMID: 18591527
7.  Nucleotide diversity and population differentiation of the Melanocortin 1 Receptor gene, MC1R 
BMC Genetics  2008;9:31.
Background
The melanocortin 1 receptor gene (MC1R) is responsible for normal pigment variation in humans and is highly polymorphic with numerous population-specific alleles. Some MC1R variants have been associated with skin cancer risk.
Results
Allele frequency data were compiled on 55 single nucleotide polymorphisms from seven geographically distinct human populations (n = 2306 individuals). MC1R nucleotide diversity, π, was much higher (10.1 × 10-4) than in other genes for all subjects. A large degree of population differentiation, determined by FST, was also present, particularly between Asia and all other populations, due to the p.R163Q (c.488 G>A) polymorphism. The least amount of differentiation was between the United States, Northern Europe, and Southern Europe. Tajima's D statistic suggested the presence of positive selection in individuals from Europe.
Conclusion
This study further quantifies the degree of population-specific genetic variation and suggests that positive selection may be present in European populations in MC1R.
doi:10.1186/1471-2156-9-31
PMCID: PMC2324112  PMID: 18402696
8.  Carcinoma cuniculatum 
doi:10.1503/cmaj.061463
PMCID: PMC1930171  PMID: 17664446
9.  Analysis of health care and actual needs of patients with psoriasis: a survey on the Italian population 
BMC Public Health  2007;7:59.
Background
Over recent years the public health system has shown increasing interest in patients' views for use as guideline criteria in evaluating the quality of assistance above all for those patients with chronic diseases. Hence the interest in psoriasis, which is a chronic disease frequently associated with diabetes mellitus, hypertension, obesity, and cardiovascular diseases. The aims of our study were to describe clinic characteristics of patients with psoriasis, the quality of the assistance perceived by patients arrived at outpatients clinics and the information received, in order to identify areas in Italy requiring improvement.
Methods
1954 patients, aged between 18 and 85 years, were consecutively enrolled at outpatients clinics across 21 Italian provinces over the period December 2004 – January 2006. A standardized questionnaire was developed in collaboration with an Italian Association of Psoriatic Patients (A.DI.PSO) and tested in a pilot study. The questionnaire was divided into three sections: the first section included social, demographic and individual variables; the second concerned the quality of the assistance perceived by the patients at public dermatologic clinics and the third focused on the need of information requirements of patients with psoriasis. The χ2 test was used to estimate the association between the categorical variables under study. Kruskal-Wallis test was applied to the interval and ordinal variables.
Results
The presence of psoriatic arthritis was reported in 26.0% of patients. Associated chronic diseases included depression (15.4%), hypertension (13.3%), obesity (8.9%) and type 2 diabetes mellitus (7.3%). The study highlighted the need of improvements of health care services at public dermatologic clinics especially in overcoming architectonic barriers and reducing appointment wait-times, particularly in South Italy. However, patients reported a positive relationship with Health System employers due to the confidentiality. This positive impression was confirmed by the observation that dermatologists were considered the best source of information about therapies on psoriasis.
Conclusion
Our study allowed to identify critical aspects which could be tackled through initiatives with the aim of improving these emerged needs.
doi:10.1186/1471-2458-7-59
PMCID: PMC1866239  PMID: 17448249
10.  Assessing the Impact of Efalizumab on Nail, Scalp and Palmoplantar Psoriasis and on Quality of Life: Results from a Multicentre, Open-label, Phase IIIb/IV Trial 
Archives of Drug Information  2009;2(4):66-70.
This post-approval, open-label trial (n = 1266) assessed the efficacy of efalizumab, administered in accordance with the European label at that time, in patients with concomitant nail, scalp or palmoplantar psoriasis. Patients received subcutaneous efalizumab 1.0 mg/kg weekly for up to 20 weeks. By Week 12, an improvement from baseline of 50% or more was observed in 21.4% (181/844) of patients with nail psoriasis, 62.4% (718/1150) of patients with scalp psoriasis, and 51.4% (127/247) of patients with palmoplantar psoriasis. Quality of life improved throughout the trial, with a 50% median improvement in DLQI score after 12 weeks of treatment. Efalizumab showed promising efficacy in the treatment of nail, scalp and palmoplantar psoriasis, which was reflected in improvements in quality of life.
doi:10.1111/j.1753-5174.2009.00023.x
PMCID: PMC2805869  PMID: 20098509
Efalizumab; Nail Psoriasis; Palmoplantar Psoriasis; Quality of Life; Scalp Psoriasis

Results 1-10 (10)