Abstract
Betel quid (BQ) products, with or without tobacco, have been classified by the International Agency for Research on Cancer (IARC) as group I human carcinogens that are associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. There are estimated 600 million BQ users worldwide. In Taiwan alone there are 2 million habitual users (approximately 10% of the population). Oral and pharyngeal cancers result from interactions between genes and environmental factors (BQ exposure). Cytochrome p450 (CYP) families are implicated in the metabolic activation of BQ- and areca nut-specific nitrosamines. In this review, we summarize the current knowledge base regarding CYP genetic variants and related oral disorders. In clinical applications, we focus on cancers of the oral cavity and pharynx and OPMDs associated with CYP gene polymorphisms, including CYP1A1, CYP2A6, CYP2E1, and CYP26B1. Our discussion of CYP polymorphisms provides insight into the importance of screening tests in OPMDs patients for the prevention of oral and pharyngeal cancers. Future studies will establish a strong foundation for the development of chemoprevention strategies, polymorphism-based clinical diagnostic tools (e.g., specific single-nucleotide polymorphism (SNP) “barcodes”), and effective treatments for BQ-related oral disorders.
Highlights
Oral and pharyngeal cancers are some of the most common cancers worldwide [1]
We found that the CYP26B1 polymorphism AA significantly correlated with the risk of oral cancer (OR = 2.26; 95% CI, 1.35–3.80), and betel quid (BQ) chewers with the AA genotype had a significantly increased risk of oral cancer (OR = 70.04; 95% CI, 13.62– 360.11)
Subjects with CYP1A1 carrying G allele increased the risk for oral potentially malignant disorders (OPMDs) and oral cancer
Summary
Oral and pharyngeal cancers are some of the most common cancers worldwide [1]. Taiwan is a hyperendemic area for oral and pharyngeal cancers [2]. Environmental carcinogens and genetic polymorphisms, either separately or jointly, play an important role in the occurrence of oral and pharyngeal cancers Environmental factors, such as alcohol use, BQ chewing, and cigarette smoking, were significantly associated with the risk of oral and pharyngeal cancers and OPMDs, and a synergistic effect among the use of these substances was observed [6, 7, 16]. Several studies have indicated that CYP polymorphisms affect the metabolism of tobacco-derived carcinogens and the risk of oral cancer [31,32,33]. Our review focuses on the role of the CYP enzyme-mediated metabolism in OPMDs and oral and pharyngeal cancers among BQ users and evaluates emerging data that potentially implicate arecolineand arecoline-derived N-nitrosamines in tumorigenesis. The effects of CYP polymorphisms are worthy of investigation to further understand the role of genetic factors in susceptibility to OPMDS and cancers of the oral cavity and pharynx and to aid the development of prevention strategies for cancers related to BQ use
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