Frequency of the Functionally Relevant Aryl Hydrocarbon Receptor Repressor (AhRR) Pro185Ala SNP in Papua New Guinea
Frequency of the Functionally Relevant Aryl Hydrocarbon Receptor Repressor (AhRR) Pro185Ala SNP in Papua New Guinea
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DOI：
10.2133/dmpk.dmpk-13-sc-035
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发表时间：
2013-12-25
影响因子：
2.1
通讯作者：
Kaneko, Akira
中科院分区：
文献类型：
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作者：
Cavaco, Isa;Hombhanje, Francis Wanak;Kaneko, Akira
巴布亚新几内亚 (PNG) 人口的文化和社会习惯多种多样，包括咀嚼槟榔和最近的吸烟。槟榔中 DNA 加合物的形成是由细胞色素 P450 (CYP) 酶（包括 CYP1A2）介导的。烟草烟雾化合物可诱导 CYP1A2。转录因子 AhR（芳烃受体）参与 CYP1A2 表达的调节。 AhR 活性本身受到其他转录因子的调节，包括芳基碳氢化合物受体阻遏物 (AhRR)。 AhRR Pro185Ala (rs2292596; 565C>G) 小等位基因最近与较低的 AhR 阻遏活性相关，导致较高的 CYP1A2 诱导能力。我们调查了巴布亚新几内亚东塞皮克人群中的 AhRR Pro185Ala SNP，发现次要等位基因的频率高达 53.4%，与其他亚洲人群显着不同。我们可以假设，由于 CYP1A2 的诱导能力较高，AhRR SNP 的高频率可能是巴布亚新几内亚口腔癌和其他肿瘤发病的危险因素。 AhRR 药物遗传学在与咀嚼槟榔和吸烟相关的癌症风险中的潜在作用应在巴布亚新几内亚未来的流行病学研究中得到解决和澄清。
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.