engleski

Association with melanoma of a polymorphic GGC repeat in the NPAS2 gene

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 (MOP4) is a clock gene that can act as a tumor suppressor. We are searching for the presence of polymorphisms in the 5’ region of NPAS2. By using Sanger sequencing and capillary electrophoresis, we found a polymorphic GGC repeat in the untranslated (first) exon of NPAS2. Allele and genotype frequencies of the GGC repeat were measured in 117 subjects affected by melanoma and 97 controls. In both groups four alleles were present, with 7, 9, 12 and 13 GGC repeats. Alleles 7 and 9 were the most frequent (either having a frequency > 30% in controls or 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 genotype frequencies. In particular, the genotype 7/9 was more frequent in controls (53.6%) than in melanoma subjects (29.0%) (p: 0.0004). No statistical difference was found for other genotypes. Therefore, the heterozygous 7/9 genotype appears to be a protective factor for melanoma.

melanoma; polymorphic GGC repeat; NPAS2 gene

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