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

Abstract

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.

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

“…A total of 85 melanoma patients and 166 healthy individuals were included in the study. Demographics and clinical characteristics of cases and control groups was reported in previous studies (14).…”

“…After quantitation using UV-Vis spectrometry, DNA samples were stored at -20˚C for future use. PCR conditions were described in the previous study (14). CDKN2A and CDK4 primers are available in Table I.…”

SLC45A2 Germilne Variants in Colombian Population with Melanoma

“…Overall Clinical and demographics characteristics of 85 cutaneous melanoma patients and 166 healthy individual was reported in previous studies [17].…”

“…The two SLC45A2 (p.Glu272Lys rs26722 and p.Phe374Leu rs16891982) variants were studied so that it has been associated with melanoma, 10 samples of cases and 10 samples of controls groups was performed with the Sanger method used to be as a control for after analysis using a Big Dye Terminator and BI PRISM 3130xl Genetic Analyzer (Applied Biosystems®). PCR conditions were described in the previous study and the SCL45A2 primers (p.Glu272Lys 5-CTGCA ⊤ GℂAGCTCTGGAT -3, 5-ℂTCAGGAℂCTℂA ⊤ GTC -3 and p.Phe374Leu 5 -GGAGAGAG ∀ AGAC ⊤ AC ∀ G ∀ T ∀ A -3, 5-TℂACAGAG ⊤ TCTCATCTACGA -3) [17]. All SNPs were genotyped using the Real-Time PCR (qPCR), and analyzed with High-Resolution Melting Analysis (HRM), all conditions were described in the previous study [17, 18].…”

“…PCR conditions were described in the previous study and the SCL45A2 primers (p.Glu272Lys 5-CTGCA ⊤ GℂAGCTCTGGAT -3, 5-ℂTCAGGAℂCTℂA ⊤ GTC -3 and p.Phe374Leu 5 -GGAGAGAG ∀ AGAC ⊤ AC ∀ G ∀ T ∀ A -3, 5-TℂACAGAG ⊤ TCTCATCTACGA -3) [17]. All SNPs were genotyped using the Real-Time PCR (qPCR), and analyzed with High-Resolution Melting Analysis (HRM), all conditions were described in the previous study [17, 18]. Statistical Analysis.…”