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.

Do polymorphisms in protein kinase catalytic subunit alpha-1 gene associated with cancer susceptibility? a meta-analysis and systematic review

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Cyclooxygenase-2 Promoter 765C Increase of Digestive Tract Cancer Risk in the Chinese Population: a Meta-analysis

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Lack of association between the cyclooxygenase 2 -765G>C polymorphism and prostate cancer risk: a meta-analysis

“…Over the last decade, numerous molecular epidemiological case-control studies have been conducted in diverse ethnic backgrounds to explore the association between the COX2 -765G>C polymorphism and risks of various cancers, including breast cancer (Piranda et al, 2010), colorectal carcinoma (Daraei et al, 2012), esophageal (Bye et al, 2011) and gastric cancers , hepatocellular carcinoma (He et al, 2012), leukemia (Zheng et al, 2011), lung cancer (Coskunpinar et al, 2011), lymphoma (Monroy et al, 2011), ovarian (Agachan Cakmakoglu et al, 2011, head and neck (Peters et al, 2009), pancreatic (Zhao et al, 2009), skin (Cocoş et al, 2012), and cervical cancers (Pandey et al, 2010), among others. However, due to the relatively small sample sizes, the results obtained from these studies have been inconclusive or even controversial.…”