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

Karagianni, Fani; Njauw, Ching‐Ni Jenny; Kypreou, Katerina P.; Stergiopoulou, Aravela; Plaka, M.; Polydorou, Dorothea; Chasapi, Vasiliki; Pappas, Leontios; Stratigos, Ioannis A.; Champsas, Gregory; Panagiotou, Peter; Gogas, Helen; Evangelou, Evangelos; Stratigos, Alexander J.; Stefanaki, Irene

doi:10.2340/00015555-2969

Cited by 8 publications

(8 citation statements)

References 37 publications

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“…The results showed that case and control groups did not display in vivo 35 A study analyzed an Australian population of 1,109 melanoma patients, but no CDK4 variants were found (18). However, prior studies reported that CDK4 variants frequencies are approximately between 2-15% in Greek (19), Latvian (20), and other populations (5). Germline variants (500C>G and 540C>T) in the CDKN2A 3'UTR gene have been found in approximately 12-31% of cutaneous melanomas and healthy controls, respectively (21)(22)(23), as well as associated with a risk of developing other types of cancer (24).…”

Section: Discussionmentioning

confidence: 94%

3’UTR-CDKN2A and CDK4 Germline Variants Are Associated With Susceptibility to Cutaneous Melanoma

Tovar-Parra

Gil‐Quiñones

Nova

et al. 2021

In Vivo

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Background/Aim: Genetic variations of the CDKN2A and CDK4 gene have been associated to melanoma development. In the present study we investigated the potential associations of CDKN2A and CDK4 gene variants in a colombian population diagnosed with melanoma. Materials and Methods: DNA was extracted from whole blood samples from 85 patients diagnosed with cutaneous melanoma and 166 healthy controls. CDKN2A and CDK4 genes were genotyped using a high-resolution melting assay. Results: A similar distribution of CDKN2A variants 500C>G and 540C>T was found among cases (12% and 31% respectively) and controls (15% and 31% respectively). The CDKN2A variants were present in 36% of acral lentiginous melanoma and 39.47% of lentigo maligna. The haplotype analysis showed an association with susceptibility in the development of melanoma. Conclusion: The presence of haplotype 500G/540C in males is associated with an increased risk of melanoma in a colombian population, especially in subjects with a family history of cancer.

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Section: Discussionmentioning

confidence: 94%

3’UTR-CDKN2A and CDK4 Germline Variants Are Associated With Susceptibility to Cutaneous Melanoma

Tovar-Parra

Gil‐Quiñones

Nova

et al. 2021

In Vivo

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“…p.V126D variant has been previously detected in North American patients with familiar history of melanoma; however, in this study, the variant was detected in patients and healthy controls without familiar history of melanoma [ 39 ]. Similarly, the p.A148T variant was detected in patients and controls; this variant has been reported in the different population as Brazilian [ 40 ], Australian [ 18 ], Israeli [ 41 ], and Greek [ 5 ].…”

Section: Discussionmentioning

confidence: 83%

“…The incidence and mortality rate has increased in recent years, with 26% in the mortality rates as reported by Globocan [ 2 , 3 ]. The etiology of melanoma is driven by the interaction between environmental factors (UV radiation) [ 4 ]; phenotypic features (red or blond hair, blue or green eyes, light skin phototypes, freckles, multiple melanocytic nevi, and the presence of nevus clinically atypical) [ 5 ]; and genotypic features such as mutations, single nucleotide polymorphisms (SNPs), and family history of melanoma [ 6 ]. SNPs have been used as markers to identify genetic susceptibility to develop any disease [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

CDKN2A Polymorphism in Melanoma Patients in Colombian Population: A Case-Control Study

Tovar-Parra

Gutiérrez-Castañeda

Gil‐Quiñones

et al. 2020

BioMed Research International

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Introduction. Melanoma is the most aggressive type of skin cancer, with poor prognosis in advanced stages. The incidence and mortality rates have increased in recent years. Single nucleotide polymorphisms p.R24P, p.M53I, p.G101W, p.V126D, and p.A148T in the CDKN2A (HGNC ID: 1787) gene have been associated with the development of melanoma in different populations; however, this association has not been studied in Colombia. Methods. Cutaneous melanoma patients and healthy controls (85 cases and 166 controls) were included in this study. These subjects were screened through HRM-qPCR assay and detected variants in exon 1 and 2 of CDKN2A gene and confirmed with Sanger sequencing. Chi-square test was used to compare allele and genotype distributions between cases and controls. Odds ratio (OR) with 95% confidence interval (CI) was calculated to determine the association between polymorphisms and haplotypes with melanoma susceptibility. Statistical and haplotype analyses were performed using Stata® and R-Studio®. Results. Fifty-four percent of women were identified both in cases and controls. The frequencies of melanoma subtypes were 36,47% lentigo maligna, 24,71% acral lentiginous, 23,53% superficial extension, and 15,29% nodular. Variants in the CDKN2A gene were 11.76% in cases and 8.43% in controls. The most frequent was p.A148T in 5.88% of cases and in 4.82% of controls. GGTTG haplotype showed statistically significant differences between cases and controls ( p value = 0.04). Conclusion. CDKN2A polymorphisms p.G101W, p.R24P, p.M53I, and A148T are not associated with melanoma susceptibility in the Colombian population; further studies regarding genetic interaction and additive effects between more variants are required.

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“…Although the low number of Greek families might have contributed to amplifying these differences, the mutation rates identified in our families are consistent with those previously reported in each country, excluding reports of higher frequency due to founder effects. 15,[43][44][45][46][47][48] A higher impact of genetic risk factors has been suggested in the Greek low incidence population. 48 A high number of affected members, early age at diagnosis and MPM are considered predictors of CDKN2A variation.…”

Section: Discussionmentioning

confidence: 99%

High‐ and intermediate‐risk susceptibility variants in melanoma families from the Mediterranean area: A multicentre cohort from the MelaNostrum Consortium

Pellegrini,

Cardelli,

Ghiorzo

et al. 2023

Acad Dermatol Venereol

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BackgroundMost of large epidemiological studies on melanoma susceptibility have been conducted on fair skinned individuals (US, Australia and Northern Europe), while Southern European populations, characterized by high UV exposure and dark‐skinned individuals, are underrepresented.ObjectivesWe report a comprehensive pooled analysis of established high‐ and intermediate‐penetrance genetic variants and clinical characteristics of Mediterranean melanoma families from the MelaNostrum Consortium.MethodsPooled epidemiological, cinical and genetic (CDKN2A, CDK4, ACD, BAP1, POT1, TERT, and TERF2IP and MC1R genes) retrospective data of melanoma families, collected within the MelaNostrum Consortium in Greece, Italy and Spain, were analyzed. Univariate methods and multivariate logistic regression models were used to evaluate the association of variants with characteristics of families and of affected and unaffected family members. Subgroup analysis was performed for each country.ResultsWe included 839 families (1365 affected members and 2123 unaffected individuals). Pathogenic/likely pathogenic CDKN2A variants were identified in 13.8% of families. The strongest predictors of melanoma were ≥2 multiple primary melanoma cases (OR 8.1;95%CI 3.3‐19.7), >3 affected members (OR 2.6; 95%CI 1.3‐5.2) and occurrence of pancreatic cancer (OR 4.8; 95%CI 2.4‐9.4) in the family (AUC 0.76, 95%CI 0.71‐0.82). We observed low frequency variants in POT1 (3.8%), TERF2IP (2.5%), ACD (0.8%) and BAP1 (0.3%). MC1R common variants (≥2 variants and ≥2 RHC variants) were associated with melanoma risk (OR 1.4;95%CI 1.0‐2.0 and OR 4.3;95%CI 1.2‐14.6, respectively).ConclusionsVariants in known high‐penetrance genes explain nearly 20% of melanoma familial aggregation in Mediterranean areas. CDKN2A melanoma predictors were identified with potential clinical relevance for cancer risk‐assessment.

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

Cited by 8 publications

References 37 publications

3’UTR-CDKN2A and CDK4 Germline Variants Are Associated With Susceptibility to Cutaneous Melanoma

3’UTR-CDKN2A and CDK4 Germline Variants Are Associated With Susceptibility to Cutaneous Melanoma

CDKN2A Polymorphism in Melanoma Patients in Colombian Population: A Case-Control Study

High‐ and intermediate‐risk susceptibility variants in melanoma families from the Mediterranean area: A multicentre cohort from the MelaNostrum Consortium

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