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Melanoma: HELP
Articles by Irene Stefanaki
Based on 11 articles published since 2008
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Between 2008 and 2019, I. Stefanaki wrote the following 11 articles about Melanoma.
 
+ Citations + Abstracts
1 Review Non-genetic risk factors for cutaneous melanoma and keratinocyte skin cancers: An umbrella review of meta-analyses. 2016

Belbasis, Lazaros / Stefanaki, Irene / Stratigos, Alexander J / Evangelou, Evangelos. ·Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece. · Department of Dermatology, Andreas Sygros Hospital, University of Athens Medical School, Athens, Greece. · Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. Electronic address: vangelis@cc.uoi.gr. ·J Dermatol Sci · Pubmed #27663092.

ABSTRACT: BACKGROUND: Skin cancers have a complex disease mechanism, involving both genetic and non-genetic risk factors. Numerous meta-analyses have been published claiming statistically significant associations between non-genetic risk factors and skin cancers without applying a thorough methodological assessment. OBJECTIVE: The present study maps the literature on the non-genetic risk factors of skin cancers, assesses the presence of statistical biases and identifies the associations with robust evidence. METHODS: We searched PubMed up to January 20, 2016 to identify systematic reviews and meta-analyses of observational studies that examined associations between non-genetic factors and skin cancers. For each meta-analysis, we estimated the summary effect size by random-effects and fixed-effects models, the 95% confidence interval and the 95% prediction interval. We also assessed the between-study heterogeneity (I RESULTS: Forty-four eligible papers were identified and included a total of 85 associations. Twenty-one associations were significant at P<10 CONCLUSION: The majority of meta-analyses on non-genetic risk factors for skin cancers suffered from large between-study heterogeneity and small-study effects or excess significance bias. The associations with convincing and highly suggestive evidence were mainly focused on skin photosensitivity and phenotypic characteristics.

2 Review Comprehensive field synopsis and systematic meta-analyses of genetic association studies in cutaneous melanoma. 2011

Chatzinasiou, Foteini / Lill, Christina M / Kypreou, Katerina / Stefanaki, Irene / Nicolaou, Vasiliki / Spyrou, George / Evangelou, Evangelos / Roehr, Johannes T / Kodela, Elizabeth / Katsambas, Andreas / Tsao, Hensin / Ioannidis, John P A / Bertram, Lars / Stratigos, Alexander J. ·Department of Dermatology, University of Athens Medical School, Andreas Sygros Hospital, Dragoumi 5, Athens 161 21, Greece. ·J Natl Cancer Inst · Pubmed #21693730.

ABSTRACT: BACKGROUND: Although genetic studies have reported a number of loci associated with cutaneous melanoma (CM) risk, a comprehensive synopsis of genetic association studies published in the field and systematic meta-analysis for all eligible polymorphisms have not been reported. METHODS: We systematically annotated data from all genetic association studies published in the CM field (n = 145), including data from genome-wide association studies (GWAS), and performed random-effects meta-analyses across all eligible polymorphisms on the basis of four or more independent case-control datasets in the main analyses. Supplementary analyses of three available datasets derived from GWAS and GWAS-replication studies were also done. Nominally statistically significant associations between polymorphisms and CM were graded for the strength of epidemiological evidence on the basis of the Human Genome Epidemiology Network Venice criteria. All statistical tests were two-sided. RESULTS: Forty-two polymorphisms across 18 independent loci evaluated in four or more datasets including candidate gene studies and available GWAS data were subjected to meta-analysis. Eight loci were identified in the main meta-analyses as being associated with a risk of CM (P < .05) of which four loci showed a genome-wide statistically significant association (P < 1 × 10(-7)), including 16q24.3 (MC1R), 20q11.22 (MYH7B/PIGU/ASIP), 11q14.3 (TYR), and 5p13.2 (SLC45A2). Grading of the cumulative evidence by the Venice criteria suggested strong epidemiological credibility for all four loci with genome-wide statistical significance and one additional gene at 9p23 (TYRP1). In the supplementary meta-analyses, a locus at 9p21.3 (CDKN2A/MTAP) reached genome-wide statistical significance with CM and had strong epidemiological credibility. CONCLUSIONS: To the best of our knowledge, this is the first comprehensive field synopsis and systematic meta-analysis to identify genes associated with an increased susceptibility to CM.

3 Article MelaNostrum: a consensus questionnaire of standardized epidemiologic and clinical variables for melanoma risk assessment by the melanostrum consortium. 2018

Stratigos, Alexander J / Fargnoli, Maria Concetta / De Nicolo, Arcangela / Peris, Ketty / Puig, Susana / Soura, Efthymia / Menin, Chiara / Calista, Donato / Ghiorzo, Paola / Mandala, Mario / Massi, Daniela / Rodolfo, Monica / Del Regno, Laura / Stefanaki, Irene / Gogas, Helen / Bataille, Veronique / Tucker, Margaret A / Whiteman, David / Nagore, Eduardo / Landi, Maria Teresa. ·First Department of Dermatology, National and Kapodistrian University of Athens School of Medicine, Andreas Sygros Hospital, Athens, Greece. · Department of Dermatology, University of L'Aquila, L'Aquila, Italy. · Cancer Genomics Program, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy. · Institute of Dermatology, Catholic University, Rome, Italy. · Dermatology Department, Melanoma Unit, Hospital Clinic de Barcelona, Universitat de Barcelona, Barcelona, Spain. · Instituto de Investigacion Biomedica August Pi i Sunyer (IDIBAPS), Barcelona, Spain. · Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain. · Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy. · Dermatology Unit, Maurizio Bufalini Hospital, Cesena, Italy. · Department of Internal Medicine and Medical Specialties, University of Genoa and Genetics of Rare Cancers, University Hospital Policlinico San Martino-IRCCS, Genoa, Italy. · Unit of Melanoma, Department of Oncology and Hematology, Papa Giovanni XXIII Cancer Center Hospital, Bergamo, Italy. · Department of Surgery and Translational Medicine, University of Florence, Florence, Italy. · Immunotherapy Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Department of Internal Medicine, Laikon Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece. · Department of Twin Research and Genetic Epidemiology, Kings College, London, UK. · Human Genetics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. · Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia. · Department of Dermatology, Instituto Valenciano de Oncología, València, Spain. ·J Eur Acad Dermatol Venereol · Pubmed #30098061.

ABSTRACT: BACKGROUND: Many melanoma observational studies have been carried out across different countries and geographic areas using heterogeneous assessments of epidemiologic risk factors and clinical variables. AIM: To develop a consensus questionnaire to standardize epidemiologic and clinical data collection for melanoma risk assessment. METHODS: We used a stepwise strategy that included: compilation of variables from case-control datasets collected at various centres of the MelaNostrum Consortium; integration of variables from published case-control studies; consensus discussion of the collected items by MelaNostrum members; revision by independent experts; addition of online tools and image-based charts; questionnaire testing across centres and generation of a final draft. RESULTS: We developed a core consensus questionnaire (MelanoQ) that includes four separate sections: A. general and demographic data; B. phenotypic and ultraviolet radiation exposure risk factors and lifestyle habits; C. clinical examination, medical and family history; and D. diagnostic data on melanoma (cases only). Accompanying online tools, informative tables, and image-based charts aid standardization. Different subsections of the questionnaire are designed for self-administration, patient interviews performed by a physician or study nurse, and data collection from medical records. CONCLUSIONS: The MelanoQ questionnaire is a useful tool for the collection and standardization of epidemiologic and clinical data across different studies, centres, cultures and languages. This will expedite ongoing efforts to compile high-quality data for pooled analyses or meta-analyses and offer a solid base for the design of clinical, epidemiologic and translational studies on melanoma.

4 Article CDKN2A/CDK4 Status in Greek Patients with Familial Melanoma and Association with Clinico-epidemiological Parameters. 2018

Karagianni, Fani / Njauw, Ching-Ni / Kypreou, Katerina P / Stergiopoulou, Aravela / Plaka, Michaela / Polydorou, Dorothea / Chasapi, Vasiliki / Pappas, Leontios / Stratigos, Ioannis A / Champsas, Gregory / Panagiotou, Peter / Gogas, Helen / Evangelou, Evangelos / Tsao, Hensin / Stratigos, Alexander J / Stefanaki, Irene. ·1st Department of Dermatology, Andreas Sygros Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. ·Acta Derm Venereol · Pubmed #29774366.

ABSTRACT: Approximately 5-10% of melanoma cases occur in a familial context. CDKN2A/CDK4 were the first high-penetrance melanoma genes identified. The aims of this study were to evaluate CDKN2A/CDK4 variants in Greek familial melanoma patients and to correlate the mutational status with specific clinico-epidemiological characteristics. A cross-sectional study was conducted by genotyping CDKN2A/CDK4 variants and selected MC1R polymorphisms in 52 melanoma-prone families. Descriptive statistics were calculated and comparisons were made using the χ2 test, Fisher's exact test and Student's t-test for statistical analysis, as appropriate. CDKN2A variants were detected in 46.2% of melanoma-prone families, while a CDK4 variant was found in only one family. This study confirmed that, in the Greek population, the age at melanoma diagnosis was lower in patients carrying a variant in CDKN2A compared with wild-type patients. No statistically significant associations were found between CDKN2A mutational status and MC1R polymorphisms.

5 Article Inherited susceptibility to melanoma: insights from a high-risk Austrian cohort. 2016

Stefanaki, I / Stratigos, A J. ·Department of Dermatology, University of Athens School of Medicine, Andreas Sygros Hospital for Skin and Venereal Diseases, 5 I. Dragoumi Street, Athens, 161 21,, Greece. · Department of Dermatology, University of Athens School of Medicine, Andreas Sygros Hospital for Skin and Venereal Diseases, 5 I. Dragoumi Street, Athens, 161 21,, Greece. alstrat@hol.gr. ·Br J Dermatol · Pubmed #27317282.

ABSTRACT: -- No abstract --

6 Article Prediction of Melanoma Risk in a Southern European Population Based on a Weighted Genetic Risk Score. 2016

Kypreou, Katerina P / Stefanaki, Irene / Antonopoulou, Kyriaki / Karagianni, Fani / Ntritsos, Georgios / Zaras, Alexios / Nikolaou, Vasiliki / Kalfa, Iro / Chasapi, Vasiliki / Polydorou, Dorothea / Gogas, Helen / Spyrou, George M / Bertram, Lars / Lill, Christina M / Ioannidis, John P A / Antoniou, Christina / Evangelou, Evangelos / Stratigos, Alexander I. ·1st Department of Dermatology, Andreas Syggros Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. · Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece, GR. · Blood Donation Unit, Laikon Hospital, Athens, Greece. · Department of Internal Medicine, University of Athens, Laikon Hospital, Athens, Greece. · Biomedical Informatics Unit, Biomedical Research Foundation, Academy of Athens, Athens, Greece. · Platform for Genome Analytics, Institutes of Neurogenetics & Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany; School of Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom. · Institute of Neurogenetics, University of Lübeck, Lübeck, Germany. · Stanford Prevention Research Center, Department of Medicine and Department of Health Research and Policy, Stanford University School of Medicine, and Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, USA. · Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece, GR; Department of Epidemiology and Biostatistics, Imperial College London, St. Mary's Campus, London, United Kingdom. · 1st Department of Dermatology, Andreas Syggros Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: alstrat@hol.gr. ·J Invest Dermatol · Pubmed #27015455.

ABSTRACT: Many single nucleotide polymorphisms (SNPs) have been described as putative risk factors for melanoma. The aim of our study was to validate the most prominent genetic risk loci in an independent Greek melanoma case-control dataset and to assess their cumulative effect solely or combined with established phenotypic risk factors on individualized risk prediction. We genotyped 59 SNPs in 800 patients and 800 controls and tested their association with melanoma using logistic regression analyses. We constructed a weighted genetic risk score (GRSGWS) based on SNPs that showed genome-wide significant (GWS) association with melanoma in previous studies and assessed their impact on risk prediction. Fifteen independent SNPs from 12 loci were significantly associated with melanoma (P < 0.05). Risk score analysis yielded an odds ratio of 1.36 per standard deviation increase of the GRSGWS (P = 1.1 × 10(-7)). Individuals in the highest 20% of the GRSGWS had a 1.88-fold increase in melanoma risk compared with those in the middle quintile. By adding the GRSGWS to a phenotypic risk model, the C-statistic increased from 0.764 to 0.775 (P = 0.007). In summary, the GRSGWS is associated with melanoma risk and achieves a modest improvement in risk prediction when added to a phenotypic risk model.

7 Article Updated field synopsis and systematic meta-analyses of genetic association studies in cutaneous melanoma: the MelGene database. 2015

Antonopoulou, Kyriaki / Stefanaki, Irene / Lill, Christina M / Chatzinasiou, Foteini / Kypreou, Katerina P / Karagianni, Fani / Athanasiadis, Emmanouil / Spyrou, George M / Ioannidis, John P A / Bertram, Lars / Evangelou, Evangelos / Stratigos, Alexander J. ·Department of Dermatology, University of Athens School of Medicine, Andreas Sygros Hospital, Athens, Greece. · Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany; Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. · Center of Systems Biology, Biomedical Research Foundation, Academy of Athens, Athens, Greece. · Department of Medicine, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, California, USA. · Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany; Department of Medicine, School of Public Health, Imperial College London, London, UK. · Department of Hygiene and Epidemiology, Clinical and Molecular Epidemiology Unit, School of Medicine, University of Ioannina, Ioannina, Greece; Department of Epidemiology and Biostatistics, Imperial College London, St Mary's Campus, London, UK. · Department of Dermatology, University of Athens School of Medicine, Andreas Sygros Hospital, Athens, Greece. Electronic address: alstrat@hol.gr. ·J Invest Dermatol · Pubmed #25407435.

ABSTRACT: We updated a field synopsis of genetic associations of cutaneous melanoma (CM) by systematically retrieving and combining data from all studies in the field published as of August 31, 2013. Data were available from 197 studies, which included 83,343 CM cases and 187,809 controls and reported on 1,126 polymorphisms in 289 different genes. Random-effects meta-analyses of 81 eligible polymorphisms evaluated in >4 data sets confirmed 20 single-nucleotide polymorphisms across 10 loci (TYR, AFG3L1P, CDK10, MYH7B, SLC45A2, MTAP, ATM, CLPTM1L, FTO, and CASP8) that have previously been published with genome-wide significant evidence for association (P<5 × 10(-8)) with CM risk, with certain variants possibly functioning as proxies of already tagged genes. Four other loci (MITF, CCND1, MX2, and PLA2G6) were also significantly associated with 5 × 10(-8)Our approach serves as a useful model in analyzing and integrating the reported germline alterations involved in CM.

8 Article A Web-based database of genetic association studies in cutaneous melanoma enhanced with network-driven data exploration tools. 2014

Athanasiadis, Emmanouil I / Antonopoulou, Kyriaki / Chatzinasiou, Foteini / Lill, Christina M / Bourdakou, Marilena M / Sakellariou, Argiris / Kypreou, Katerina / Stefanaki, Irene / Evangelou, Evangelos / Ioannidis, John P A / Bertram, Lars / Stratigos, Alexander J / Spyrou, George M. ·Center of Systems Biology, Biomedical Research Foundation, Academy of Athens, Soranou Ephessiou 4, 115 27 Athens, GR, Greece, Department of Dermatology, University of Athens, School of Medicine, Andreas Sygros Hospital, Ι. Dragoumi 5, 161 21 Athens, GR, Greece, Department of Vertebrate Genomics, Neuropsychiatric Genetics Group, Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, DE, Germany, Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, DE, Germany, Department of Hygiene and Epidemiology, Clinical and Molecular Epidemiology Unit, School of Medicine, University of Ioannina, 451 10 Ioannina, GR, Greece, Department of Epidemiology and Biostatistics, Imperial College London, St Mary's Campus, Norfolk Place, W2 1PG, London, UK, Department of Medicine Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA, Department of Health Research and Policy, Stanford Prevention Research Center, Stanford University School of Medicine, CA, USA, Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, CA, USA and Department of Medicine, School of Public Health, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London, UK. · Center of Systems Biology, Biomedical Research Foundation, Academy of Athens, Soranou Ephessiou 4, 115 27 Athens, GR, Greece, Department of Dermatology, University of Athens, School of Medicine, Andreas Sygros Hospital, Ι. Dragoumi 5, 161 21 Athens, GR, Greece, Department of Vertebrate Genomics, Neuropsychiatric Genetics Group, Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, DE, Germany, Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, DE, Germany, Department of Hygiene and Epidemiology, Clinical and Molecular Epidemiology Unit, School of Medicine, University of Ioannina, 451 10 Ioannina, GR, Greece, Department of Epidemiology and Biostatistics, Imperial College London, St Mary's Campus, Norfolk Place, W2 1PG, London, UK, Department of Medicine Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA, Department of Health Research and Policy, Stanford Prevention Research Center, Stanford University School of Medicine, CA, USA, Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, CA, USA and Department of Medicine, School of Public Health, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London, UK Center of Systems Biology, Biomedical Research Foundation, Academy of Athens, Soranou Ephessiou 4, 115 27 Athens, GR, Greece, Department of Dermatology, University of Athens, School of Medicine, Andreas Sygros Hospital, Ι. Dragoumi 5, 161 21 Athens, GR, Greece, Department of Vertebrate Genomics, Neuropsychiatric Genetics Group, Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, DE, Germany, Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, DE, Germany, Department of Hygiene and Epidemiology, Clinical and Molecular Epidemio · Center of Systems Biology, Biomedical Research Foundation, Academy of Athens, Soranou Ephessiou 4, 115 27 Athens, GR, Greece, Department of Dermatology, University of Athens, School of Medicine, Andreas Sygros Hospital, Ι. Dragoumi 5, 161 21 Athens, GR, Greece, Department of Vertebrate Genomics, Neuropsychiatric Genetics Group, Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, DE, Germany, Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, DE, Germany, Department of Hygiene and Epidemiology, Clinical and Molecular Epidemiology Unit, School of Medicine, University of Ioannina, 451 10 Ioannina, GR, Greece, Department of Epidemiology and Biostatistics, Imperial College London, St Mary's Campus, Norfolk Place, W2 1PG, London, UK, Department of Medicine Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA, Department of Health Research and Policy, Stanford Prevention Research Center, Stanford University School of Medicine, CA, USA, Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, CA, USA and Department of Medicine, School of Public Health, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London, UK gspyrou@bioacademy.gr. ·Database (Oxford) · Pubmed #25380778.

ABSTRACT: The publicly available online database MelGene provides a comprehensive, regularly updated, collection of data from genetic association studies in cutaneous melanoma (CM), including random-effects meta-analysis results of all eligible polymorphisms. The updated database version includes data from 192 publications with information on 1114 significantly associated polymorphisms across 280 genes, along with new front-end and back-end capabilities. Various types of relationships between data are calculated and visualized as networks. We constructed 13 different networks containing the polymorphisms and the genes included in MelGene. We explored the derived network representations under the following questions: (i) are there nodes that deserve consideration regarding their network connectivity characteristics? (ii) What is the relation of either the genome-wide or nominally significant CM polymorphisms/genes with the ones highlighted by the network representation? We show that our network approach using the MelGene data reveals connections between statistically significant genes/ polymorphisms and other genes/polymorphisms acting as 'hubs' in the reconstructed networks. To the best of our knowledge, this is the first database containing data from a comprehensive field synopsis and systematic meta-analyses of genetic polymorphisms in CM that provides user-friendly tools for in-depth molecular network visualization and exploration. The proposed network connections highlight potentially new loci requiring further investigation of their relation to melanoma risk. Database URL: http://www.melgene.org.

9 Article Replication and predictive value of SNPs associated with melanoma and pigmentation traits in a Southern European case-control study. 2013

Stefanaki, Irene / Panagiotou, Orestis A / Kodela, Elisavet / Gogas, Helen / Kypreou, Katerina P / Chatzinasiou, Foteini / Nikolaou, Vasiliki / Plaka, Michaela / Kalfa, Iro / Antoniou, Christina / Ioannidis, John P A / Evangelou, Evangelos / Stratigos, Alexander J. ·Department of Dermatology, University of Athens Medical School, Andreas Sygros Hospital, Athens, Greece. ·PLoS One · Pubmed #23393597.

ABSTRACT: BACKGROUND: Genetic association studies have revealed numerous polymorphisms conferring susceptibility to melanoma. We aimed to replicate previously discovered melanoma-associated single-nucleotide polymorphisms (SNPs) in a Greek case-control population, and examine their predictive value. METHODS: Based on a field synopsis of genetic variants of melanoma (MelGene), we genotyped 284 patients and 284 controls at 34 melanoma-associated SNPs of which 19 derived from GWAS. We tested each one of the 33 SNPs passing quality control for association with melanoma both with and without accounting for the presence of well-established phenotypic risk factors. We compared the risk allele frequencies between the Greek population and the HapMap CEU sample. Finally, we evaluated the predictive ability of the replicated SNPs. RESULTS: Risk allele frequencies were significantly lower compared to the HapMap CEU for eight SNPs (rs16891982--SLC45A2, rs12203592--IRF4, rs258322--CDK10, rs1805007--MC1R, rs1805008--MC1R, rs910873--PIGU, rs17305573--PIGU, and rs1885120--MTAP) and higher for one SNP (rs6001027--PLA2G6) indicating a different profile of genetic susceptibility in the studied population. Previously identified effect estimates modestly correlated with those found in our population (r = 0.72, P<0.0001). The strongest associations were observed for rs401681-T in CLPTM1L (odds ratio [OR] 1.60, 95% CI 1.22-2.10; P = 0.001), rs16891982-C in SCL45A2 (OR 0.51, 95% CI 0.34-0.76; P = 0.001), and rs1805007-T in MC1R (OR 4.38, 95% CI 2.03-9.43; P = 2×10⁻⁵). Nominally statistically significant associations were seen also for another 5 variants (rs258322-T in CDK10, rs1805005-T in MC1R, rs1885120-C in MYH7B, rs2218220-T in MTAP and rs4911442-G in the ASIP region). The addition of all SNPs with nominal significance to a clinical non-genetic model did not substantially improve melanoma risk prediction (AUC for clinical model 83.3% versus 83.9%, p = 0.66). CONCLUSION: Overall, our study has validated genetic variants that are likely to contribute to melanoma susceptibility in the Greek population.

10 Article Comprehensive mutational analysis of CDKN2A and CDK4 in Greek patients with cutaneous melanoma. 2011

Nikolaou, V / Kang, X / Stratigos, A / Gogas, H / Latorre, M C / Gabree, M / Plaka, M / Njauw, C N / Kypreou, K / Mirmigi, I / Stefanaki, I / Tsao, H. ·Department of Dermatology, University of Athens Medical School, 'A. Sygros' Hospital, I Dragoumi 5, 16121 Athens, Greece. ·Br J Dermatol · Pubmed #21801156.

ABSTRACT: BACKGROUND: The penetrance of CDKN2A mutations is subject to geographical and latitudinal variation and is presumably dictated by ultraviolet radiation exposure and possibly other co-inherited genetic factors. The frequency of mutations increases with the number of family members affected and the number of primary tumours, and also fluctuates with geography. To date, little is known about the prevalence of CDKN2A mutations in patients with melanoma from Greece. OBJECTIVE: To characterize the frequency of CDKN2A and CDK4 mutations in a hospital-based population of Greek patients with melanoma. METHODS: Three hundred and four consecutive single primary melanoma (SPM), nine familial melanoma (FM) and seven multiple primary melanoma cases (MPM) were assessed for sequence variants in exons 1α, 1β and 2 of CDKN2A and exon 2 of CDK4. RESULTS: Germline CDKN2A mutations were detected in 10 of 304 SPM (3·3%), in four of seven MPM (57%) and in two of nine FM (22%) cases. The most common mutation was a Northern European allele (p16 p.R24P) detected in eight individuals. Five previously unreported CDKN2A variants were also identified: -34G>C, c.41_43delins20bp, c.301G>C (p.G101R), c.301G>A (p.G101E) and c.296_297insGACC. We also describe the first report of a CDK4 p.R24H substitution in a Greek family. CONCLUSIONS: The Greek population appears to harbour a higher prevalence of the CDKN2A mutation than other reported cohorts. This supports the notion that genetic susceptibility may play a stronger influence in a country with a relatively low incidence of melanoma. Furthermore, the identification of Northern European alleles suggests that gene migration may be responsible, in part, for the observed cases in Greece.

11 Article Risk associations of melanoma in a Southern European population: results of a case/control study. 2008

Nikolaou, Vasiliki A / Sypsa, Vana / Stefanaki, Irene / Gogas, Helen / Papadopoulos, Othon / Polydorou, Dorothea / Plaka, Michaela / Tsoutsos, Dimosthenis / Dimou, Anastasia / Mourtzoukou, Eleni / Korfitis, Valantis / Hatziolou, Eftihia / Antoniou, Christina / Hatzakis, Angelos / Katsambas, Andreas / Stratigos, Alexander J. ·Department of Dermatology, University of Athens, Andreas Sygros Hospital, 5 Dragoumi Street, Athens, 10671, Greece. ·Cancer Causes Control · Pubmed #18307049.

ABSTRACT: OBJECTIVES: Limited data exist about the risk factors of melanoma in the Greek population. We investigated the association of melanoma with phenotypic and solar indices in this darker skin population residing in an environment of high ambient ultraviolet radiation. METHODS: Our study included 200 sporadic melanoma cases and 200 age-, sex-matched control subjects. Information on history of sun exposure patterns and cutaneous reaction to sunlight was obtained and a clinical evaluation of pigmentary traits, pigmented lesions, and actinic keratoses was performed. RESULTS: In the multivariate analysis, fair skin (OR: 4.63, for fair skin versus light brown, 95% CI: 1.54-13.92), intermittent sun exposure during childhood (OR: 3.33, >2 weeks/year of sun exposure versus < or =2 weeks/year 95% CI: 1.37-8.09), and outdoor leisure activities (OR: 2.74, 95% CI: 1.28-5.89), but not skin phototype or sunburns, were positively related to the risk of melanoma. In addition to an elevated count of common melanocytic nevi (OR: 6.27, > or =10 nevi versus no nevi, 95% CI: 1.65-23.76) and the presence of clinically atypical nevi (OR: 2.84, 95% CI: 1.16-6.98), solar lentigenes were an independent risk factor of melanoma (OR: 4.33, 95% CI: 1.67-11.22). CONCLUSIONS: Intermittent sun exposure of moderate intensity during childhood/adolescence and outdoor leisural activities, in conjunction with a more resistant skin phenotype to acute sunburns and a strong association with nevi and solar lentigenes was a prominent determinant of melanoma risk in our population.