Abstract

Abstract Purpose: Methylation of CpG islands in the promoter regions of genes plays an important role in head and neck carcinogenesis. Overexpression of COX2 gene was recorded in various types of cancer in literature. In addition, the promoter region of the COX2 gene displayed high methylation in normal colorectal tissue and normal gastric tissue samples. On the other hand, it has recently been reported in two different gastrointestinal cancer studies, that low expression of COX2 was observed in some colorectal/gastric cancers and hypermethylation/related transcriptional silencing of COX2 gene is common in colorectal cancer. There is no study investigating the COX2 methylation status on head and neck cancer (HNC) in the literature. In our study we evaluated the COX2 gene promoter methylation in patients with HNC. Experimental Design: Methylation of the COX2 was investigated by bisulfite modification/methylation-specific polymerase chain reaction in tumors and matched normal tissue samples from 99 Turkish patients with HNC. Results: The promoter region of the COX2 was methylated in 53.5% and 65.6% of the primary tumors and the corresponding normal tissue samples, respectively [p = 0.082, χ2 = 3.02, OR(95%CI) = 0.602 (0.34-1.06)]. Considering the methylation levels observed in our previous studies, and published data on different cancer types, methylation levels <10% were considered unmethylated, whereas levels between 10% to 25% and 25% to 100% were classified as moderate and high methylation, respectively. Based on this information, methylation ratio was observed less than 10% in 46.5% and 34.3% of tumor and normal samples, respectively. The moderate methylation levels (10-25%) were found in 23.2% of the tumors and 7.1% of the adjacent normal tissues. High methylation levels (>25%) were 30.3% and 58.6% in the tumor and normal tissues, respectively (p = 0.00006, χ2 = 19.24). The results were similar when a subgroup of 60 patients with larynx cancer from this cohort, were analyzed separately (p = 0.0006, χ2 = 14.87). Conclusions: Methylation may play an important role in HNC carcinogenesis. Although we found that there was no significant association between the methylation levels of tumor and adjacent normal tissues, high methylation levels of the COX2 gene were observed (>25%) in normal matched tissues when compared to the levels in HNC tumors. Citation Format: Semra Demokan, Cansu Ozkoklesen, Zubeyde Yalniz, Necati Enver, Murat Ulusan, Nejat Dalay. Analysis of promoter methylation levels of COX2 gene in Turkish patients with head and neck cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1059. doi:10.1158/1538-7445.AM2015-1059

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