title: Association of promoter polymorphism -765G>C in the PTGS2 gene with malignant melanoma in Italian patients and its correlation to gene expression in dermal fibroblasts.
abstract: Prostaglandins, especially prostaglandin E synthetase (PGE2), influence carcinogenesis by promoting cell proliferation, inhibiting apoptosis, stimulating angiogenesis and mediating immune suppression. Cyclooxygenase-2, coded by the PTGS2 gene, is the key enzyme in the production of prostaglandins. In melanoma, Cox-2 is over expressed in primary malignant melanoma (MM) and in their corresponding metastases. Polymorphisms in the promoter region of PTGS2 gene can modulate gene expression and could modify individual susceptibility to MM. Two hundred and forty melanoma patients and 342 controls were genotyped for polymorphisms -765G>C (rs20417) and -1195A>G (rs689466). Allele -765C frequency was significantly higher in melanoma patients. No allele frequency differences for -1195A>G polymorphism were observed. Haplotype analysis revealed that the haplotypes carrying the minor alleles were associated to a higher risk of melanoma (P = 0.02). Expression analysis showed that allele -765C is associated to a higher gene expression and could represent a risk allele by affecting the functionality of the promoter.
authors: Section of Biology and Genetics, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
authors: Macarena
authors: M
authors: Gomez-Lira
authors: Silvia
authors: S
authors: Ferronato
authors: Giovanni
authors: G
authors: Malerba
authors: Mario
authors: M
authors: Santinami
authors: Andrea
authors: A
authors: Maurichi
authors: Antonella
authors: A
authors: Sangalli
authors: Alberto
authors: A
authors: Turco
authors: Paola
authors: P
authors: Perego
authors: Monica
authors: M
authors: Rodolfo
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D015870:Gene Expression; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008297:Male; D008545:Melanoma / Q000201:enzymology* / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012867:Skin / Q000201:enzymology; D012878:Skin Neoplasms / Q000201:enzymology* / Q000235:genetics*
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: PTGS2; expression analysis; malignant melanoma; promoter polymorphisms