白种人口腔和口咽癌的病例对照研究以及八种代谢酶的基因变异
Case-control study of oral and oropharyngeal cancer in whites and genetic variation in eight metabolic enzymes.
作者信息
Buch Shama C, Nazar-Stewart Valle, Weissfeld Joel L, Romkes Marjorie
机构信息
Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
出版信息
Head Neck. 2008 Sep;30(9):1139-47. doi: 10.1002/hed.20867.
BACKGROUND
Genetic variation in xenobiotic metabolizing enzymes may explain differing susceptibilities to the cancer causing effects of tobacco and alcohol.
METHODS
We compared 203 oral squamous cell carcinoma cases and 416 controls for single nucleotide polymorphisms (SNPs) in 8 genes (CYP1A1, CYP2E1, MPO, mEH, GSTM1, GSTT1, GSTP1, and NAT2). Except for NAT2, genotype frequencies were similar in the 2 groups. We classified subjects as fast or slow NAT2 acetylators genotyping 13 NAT2 SNPs.
RESULTS
Fast acetylators were overrepresented in cases (53.7%) compared with controls (43.9%; odds ratio (OR) 1.55, 95% confidence interval (CI) 1.08-2.20; p value = .03). Gene-gene interaction testing suggested several cancer-NAT2 associations, with association strongest among persons without a CYP1A1 variant (*2C or *4) allele (OR 1.77, 95% CI 1.20-2.60, p value = .03) or with a variant MPO (463A) allele (OR 2.38, 95% CI 1.34-4.21, p value = .05).
CONCLUSION
These results implicate fast NAT2 acetylation as a risk factor for oral cancer.
背景
异生物素代谢酶的基因变异可能解释对烟草和酒精致癌作用的易感性差异。
方法
我们比较了203例口腔鳞状细胞癌病例和416例对照在8个基因（CYP1A1、CYP2E1、MPO、mEH、GSTM1、GSTT1、GSTP1和NAT2）中的单核苷酸多态性（SNP）。除NAT2外，两组的基因型频率相似。我们通过对13个NAT2 SNP进行基因分型，将受试者分为快速或慢速NAT2乙酰化者。
结果
与对照组（43.9%）相比，病例组中快速乙酰化者的比例过高（53.7%）；比值比（OR）为1.55，95%置信区间（CI）为1.08 - 2.20；p值 = 0.03）。基因-基因相互作用测试表明存在几种癌症与NAT2的关联，在没有CYP1A1变异（2C或4）等位基因的人群中关联最强（OR 1.77，95% CI 1.20 - 2.60，p值 = 0.03），或与变异的MPO（463A）等位基因相关（OR 2.38，95% CI 1.34 - 4.21，p值 = 0.05）。
结论
这些结果表明快速NAT2乙酰化是口腔癌的一个危险因素。
Zotero 插件