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芳香胺 N-乙酰基转移酶 2 多态性与肺癌和结直肠癌风险。

Polymorphisms of arylamine N-acetyltransferase2 and risk of lung and colorectal cancer.

机构信息

Department of Applied Biology, University of Sharjah, Sharjah, United Arab Emirates. ; Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid, Jordan.

出版信息

Genet Mol Biol. 2012 Dec;35(4):725-33. doi: 10.1590/S1415-47572012005000074. Epub 2012 Nov 9.

Abstract

The arylamine N-acetyltransferase 2 (NAT2) enzymes detoxify a wide range of naturally occurring xenobiotics including carcinogens and drugs. Point mutations in the NAT2 gene result in the variant alleles M1 (NAT2 5A), M2 (NAT26A), M3 (NAT2*7) and M4 (NAT2 *14A) from the wild-type WT (NAT2 *4) allele. The current study was aimed at screening genetic polymorphisms of NAT2 gene in 49 lung cancer patients, 54 colorectal cancer patients and 99 cancer-free controls, using PCR-RFLP. There were significant differences in allele frequencies between lung cancer patients and controls in the WT, M2 and M3 alleles (p < 0.05). However, only M2 and M3 allele frequencies were different between colorectal cancer patients and controls (p < 0.05). There was a marginal significant difference in the distribution of rapid and slow acetylator genotypes between lung cancer patients and controls (p = 0.06 and p = 0.05, respectively), but not between colorectal cancer patients and controls (p = 1.0 and p = 0.95, respectively). Risk of lung cancer development was found to be lower in slow acetylators [odds ratio (OR): 0.51, 95% confidence interval (95% CI): 0.25, 1.02, p-value = 0.07]. No effect was observed in case of colorectal cancer. Our results showed that NAT2 genotypes and phenotypes might be involved in lung cancer but not colorectal cancer susceptibility in Jordan.

摘要

芳香胺 N-乙酰基转移酶 2(NAT2)酶能够解毒多种天然存在的外源性化学物质,包括致癌物和药物。NAT2 基因的点突变导致野生型 WT(NAT24)等位基因产生变体等位基因 M1(NAT25A)、M2(NAT26A)、M3(NAT27)和 M4(NAT2*14A)。本研究旨在通过 PCR-RFLP 方法在 49 例肺癌患者、54 例结直肠癌患者和 99 例无癌症对照中筛选 NAT2 基因的遗传多态性。WT、M2 和 M3 等位基因在肺癌患者和对照组之间的等位基因频率存在显著差异(p<0.05)。然而,只有 M2 和 M3 等位基因频率在结直肠癌患者和对照组之间存在差异(p<0.05)。肺癌患者和对照组之间快速和慢速乙酰化基因型的分布存在边缘显著差异(p=0.06 和 p=0.05),但结直肠癌患者和对照组之间无差异(p=1.0 和 p=0.95)。我们发现,慢速乙酰化剂发生肺癌的风险较低(比值比(OR):0.51,95%置信区间(95%CI):0.25,1.02,p 值=0.07)。但在结直肠癌中未观察到这种效应。我们的结果表明,NAT2 基因型和表型可能与肺癌易感性有关,但与结直肠癌易感性无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05b6/3526077/a9a744b56826/gmb-35-725-g001.jpg

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