CYP26A1 Is a Novel Biomarker for Betel Quid-Related Oral and Pharyngeal Cancers.

Ping-Ho Chen,Che-Wei Wu,Chia-Min Chung,Hurng-Wern Huang,Lee-Shuan Lin,Leong-Perng Chan,Shyng-Shiou Yuan,Yen-Yun Wang,Bin Huang,Ka-Wo Lee

doi:10.3390/diagnostics10110982

Abstract

Betel quid (BQ) has been classified as a Group I human carcinogen in light of evidence demonstrating an association with an elevated risk of oral and pharyngeal cancers. To date, the incidence rate of oral and pharynx cancers among Taiwanese men ranks the highest worldwide. However, no study has yet confirmed variants of CYP26A1 was associated with the risks of oral and pharyngeal cancers. A case-control study was conducted (n = 339). CYP26A1 polymorphism was performed using SNP assay. Real-time qRT-PCR and Western blotting were used to determine the levels of CYP26A1 expression. The cancer cell model involved treatment with arecoline. Our findings showed that the downregulation of CYP26A1 mRNA and protein expression are more frequently observed in cancerous tissues than adjacent normal tissues in patients with oral and pharynx cancers (p < 0.01). We found that CYP26A1 was downregulated as the arecoline dose increased. We hypothesized that lower levels of CYP26A1 mRNA expression can be utilized a clinically biomarker causes oral and pharynx cancers. Arecoline appears to modulate CYP26A1 expression through specific pathways. Carriers of CYP26A1 SNP, rs2068888 (G/G)/rs4418728 (G/G) and who have lower levels of CYP26A1 expression are associated with an increased risk of oral and pharyngeal cancers.

Highlights

600 million people worldwide chew betel quid (BQ), a habit that is strongly associated with oral and pharyngeal cancers [1,2]
We found that the downregulation of CYP26A1 expression may play an important role in the occurrence of oral and pharyngeal cancers
Our results have revealed an important insight into the impact of Betel quid (BQ) chewing on the two single nucleotide polymorphisms (SNPs), rs2068888 or into the impact of BQ chewing on the two single nucleotide polymorphisms (SNPs), rs2068888 or rs4418728, of CYP26A1, and oral and pharyngeal cancer risk (rs2068888, odds ratio (OR) = 5.0; 95% confidence interval (CI)

Summary

Introduction

600 million people worldwide chew betel quid (BQ), a habit that is strongly associated with oral and pharyngeal cancers [1,2]. A positive correlation has been demonstrated between BQ chewing rates and the incidence oral and pharyngeal cancers in different countries [3]. In Taiwan, it is estimated that about over two million people chew BQ, composed mainly of men An enhanced risk of cancer was found in vitamin A deficient animals [8,10,11]. Vitamin A deficiency increases susceptibility to chemical carcinogens and is associated with a higher risk of cancer incidence [10]. RA plays a crucial role in the growth regulation and differentiation of normal, premalignant, and malignant cell types, especially epithelial cells, and this role is primarily mediated via its interaction with two types of nuclear RA receptors: retinoic acid receptors (RARs) and retinoic acid X receptors (RXRs) [10]

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