Skin Cancer Awareness and Preventive Behaviors in Rural Communities of Western Greece

Background: Cutaneous melanoma is the most aggressive skin cancer, responsible for most skin cancer-related deaths.About 10% of melanomas are heritable, occurring in familial settings or as part of cancer syndromes.Genetic testing primarily targets high-risk genes, with CDKN2A mutations accounting for ~20% of familial melanoma cases.Mutations in CDK4, BAP1, and telomere-related genes, such as POT1 and TERT, contribute an additional ~5% of inherited melanomas.Methods: We analysed blood DNA from 108 melanoma patients using a gene panel including CDKN2A, CDK4, and telomere-related genes (POT1, TERT).The cohort included patients with a family history of melanoma, early-onset disease (<40 years), or multiple primary melanomas.Patients with variants in telomere-related genes underwent telomere length measurement using qPCR, with -globin as a reference gene.Additional age-and sex-matched melanoma patients without familial history or mutations in analysed genes (n=54) and healthy controls were included (n=56) in the study.Telomere length was calculated using the 2^-CT method (CT =2^(CT -globin -CT tel ).In statistical analyses we used one-way ANOVA and t-tests.Results: Telomere-related gene variants were detected in 11 patients.A POT1 nonsense variant (p.Leu153*) was found in a patient with a family history of brain, breast, and lung cancers.A POT1 splice donor variant (c.546+1G>A) was identified in a 28year-old patient with lung and breast cancers in the family.A POT1 variant (p.Gly404Val) was found in a patient with familial pancreatic cancer.Seven early-onset melanoma patients (<40 years) had TERT variants: p.Ala279Thr (n=4), p.Ala1062Thr (n=2), and p. His815Arg (n=1), previously linked to esophageal, lung, and blood cancers.No significant differences in telomere length were observed between patients with variants in telomere-related genes, primary melanoma patients, and controls.However, patients with POT1 variants (c.546+1G>A and p.Leu153*) showed longer telomeres.CT values for c.546+1G>A were 0.295 vs. 0.168 in non-mutated melanoma patients and 0.169 in controls, and for p.Leu153*, 0.325 vs. 0.209 and 0.184, respectively.Conclusions: Genetic variants in telomere-related genes were not statistically significant associated with telomere length, likely due to the small cohort size.However, longer telomeres in POT1 mutation carriers suggest potential telomere dysregulation, warranting further studies.