title: Role of COX-2 activity and CRP levels in patients with non-melanoma skin cancer. -765G>C PTGS2 polymorphism and NMSC risk.
abstract: Non-melanoma skin cancer is one of the most common of all cancers and the incidence has increased in the last years as a result of many factors including increased tanning, life style and possible global climate change. Inflammation plays an important role in cancer development and is frequently evaluated by serum C-reactive protein (CRP) levels. PTGS2 -765C allele coding for COX-2 has been found to be associated with lower plasma levels of CRP. The objectives of this study are: evaluation of the association between PTGS2 -765G>C polymorphism and the occurrence of non-melanoma skin cancer, the relationship between this polymorphism and cyclooxygenase-2 activity in skin tissue, as well as the correlation with serum CRP levels in patients with non-melanoma skin cancer. We used PCR-RFLP technique to explore -765G>C PTGS2 gene polymorphism, colorimetric analysis for cyclooxygenase-2 activity in skin tissue and immunoturbidimetric assay for CRP serum levels in 174 patients with non-melanoma skin cancer [54 patients with basal cell carcinoma (BCC) and 120 patients with squamous cell carcinoma (SCC)] and 80 healthy subjects. PTGS2 -765G>C polymorphism failed to show an association with non-melanoma skin cancer risk. We observed a significant increase in COX-2 activity in SCC and BCC patients compared to control tissue (0.58 ± 0.11 and 0.63 ± 0.09 U/mg protein, respectively vs. 0.16 ± 0.01 U/mg protein). BCC and SCC intra-group analysis showed lower COX-2 activity in C-allele carriers versus non-carriers (p < 0.001 and p < 0.0001, respectively). In BCC and SCC patients with GG genotype, CRP level is significantly increased compared to control group (p < 0.0001 and p < 0.0001, respectively). Intra-group comparison of CRP levels showed significantly lower CRP levels in patients carrying C-allele compared to GG homozygotes in BCC (p = 0.0001) and SCC patients (p < 0.0001). PTGS2 -765G>C polymorphism failed to show an association with non-melanoma skin cancer risk. Regarding prognostic indicators, no consistent association emerged between PTGS2 -765G>C polymorphism and COX-2 activity or CRP levels.
authors.affiliation: Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Relu
authors.initials: R
authors.lastname: Cocoş
authors.forename: Sorina
authors.initials: S
authors.lastname: Schipor
authors.forename: Ilinca
authors.initials: I
authors.lastname: Nicolae
authors.forename: Cecilia
authors.initials: C
authors.lastname: Thomescu
authors.forename: Florina
authors.initials: F
authors.lastname: Raicu
mesh_terms: D002097:C-Reactive Protein / Q000032:analysis* / Q000235:genetics; D002280:Basal Cell Carcinoma / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012867:Skin / Q000201:enzymology; D012878:Skin Neoplasms / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D002097:C-Reactive Protein; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human