title: Frequency of the functionally relevant aryl hydrocarbon receptor repressor (AhRR) Pro185Ala SNP in Papua New Guinea.
abstract: The diverse cultural and social habits of the Papua New Guinea (PNG) population include betel quid chewing and more recently smoking. The formation of DNA adducts from betel quid is mediated by the cytochrome P450 (CYP) enzymes, including CYP1A2. The tobacco smoke compounds can induce CYP1A2. The transcription factor AhR (aryl hydrocarbon receptor) is involved in the regulation of CYP1A2 expression. AhR activity is itself regulated by other transcription factors, including the aryl hydrocarbon receptor repressor (AhRR). The AhRR Pro185Ala (rs2292596; 565C>G) minor allele was recently associated with a lower AhR repressor activity, leading to a higher CYP1A2 inducibility. We investigated AhRR Pro185Ala SNP in the East Sepik populations in PNG and found a high frequency of 53.4% of the minor allele, significantly different from other Asian populations. We can hypothesize that a high frequency of the AhRR SNP can be a risk factor in the incidence of oral cancer and other neoplasias in PNG due to higher inducibility of CYP1A2. The potential role of AhRR pharmacogenetics in the risk of developing cancers associated with betel quid chewing and smoking should be addressed and clarified in future epidemiological studies in PNG.
authors: Institute of Biotechnology and Bioengineering, Center of Molecular and Structural Biomedicine, University of Algarve.
authors: Isa
authors: I
authors: Cavaco
authors: Francis Wanak
authors: FW
authors: Hombhanje
authors: José Pedro
authors: JP
authors: Gil
authors: Akira
authors: A
authors: Kaneko
mesh_terms: D001114:Areca / Q000009:adverse effects; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005787:Gene Frequency; D006801:Humans; D015994:Incidence; D044468:Native Hawaiian or Pacific Islander / Q000235:genetics*; D010219:Papua New Guinea; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; C492162:AHRR protein, human