engleski

A polymorphic GGC repeat in the NPAS2 gene and its association with melanoma

Circadian rhythms are influenced by the expression of clock genes, which are controlled by a feedback mechanism that allows a rhythmic variation during 24 hours. Various evidences indicate that clock genes are important in neoplastic transformation. NPAS2 is the largest circadian gene. Experimental evidence suggest involvement of NPAS2 in tumorogenesis and cancer growth as a tumour suppressor. We investigated the presence of polymorphisms in the 5’ region of NPAS2 gene. The study included 72 melanoma patients and 77 control subjects (healthy blood donors). A polymorphic GGC repeat in the untranslated (first) exon of NPAS2 was found using Sanger sequencing and capillary electrophoresis. The same method was used to measure allele and genotype frequencies of the GGC repeat in all included subjects. In both groups four alleles were present, with 7, 9, 12 and 13 GGC repeats. Alleles 7 and 9 were the most frequent (frequency > 40% in controls and melanoma subjects). In both groups, allele and genotype frequencies were in Hardy-Weinberg equilibrium. In terms of allelic frequencies no statistical difference was found between melanoma and control subjects. In contrast, significant differences were found in particular genotype frequencies: the genotype 7/9 was more frequent in controls than in melanoma subjects (57.1% vs 34.7% ; p=0.0084) ; the genotype 9/9 was more frequent in melanoma subjects than in controls (26.3% vs 9.0% ; p=0.0087). No statistical difference was found for other genotypes. The homozygous genotype of the 9 GGC repeat of the NPAS2 gene could be a susceptibility factor for melanoma.

NPAS2 gene; clock genes; melanoma; cancer susceptibility; genetics

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