Lubin Jay H, Kogevinas Manolis, Silverman Debra, Malats Núria, Garcia-Closas Montserrat, Tardón Adonina, Hein David W, Garcia-Closas Reina, Serra Consol, Dosemeci Mustafa, Carrato Alfredo, Rothman Nathaniel
Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., Rockville, MD 20852, USA.
Int J Epidemiol. 2007 Feb;36(1):236-41. doi: 10.1093/ije/dym043.
The N-acetyltransferase 2 (NAT2) enzyme detoxifies aromatic amines, an important class of carcinogens in tobacco smoke. Slow acetylation phenotype individuals have reduced detoxification capacity compared with those with a rapid/intermediate phenotype. Analysis of the Spanish Bladder Cancer Study found an odds ratio (OR) for slow acetylators relative to rapid/intermediate acetylators of 0.9 in never-smokers and 1.6 in ever-smokers, a 1.8-fold enhancement in smokers. Evidence indicates that acetylation is an exposure-dependent process, and thus the magnitude of the interaction may also depend on exposure level.
We extend a comprehensive three-parameter linear-exponential model for the excess odds ratio (EOR) for smoking to include effects of NAT2 status, and reanalyse smoking and NAT2 status for the bladder cancer data.
We show that variations in smoking risk with NAT2 status result from interactions with smoking intensity (cigarettes per day) and not total pack-years of exposure. In addition, the relative increase in smoking risk in NAT2 slo acetylators increases with smoking intensity.
Analyses reveal an enhanced effect for smoking intensity and bladder cancer in NAT2 slow acetylators which increases with intensity.
N - 乙酰基转移酶2（NAT2）可使芳香胺解毒，芳香胺是烟草烟雾中一类重要的致癌物。与快速/中间乙酰化表型个体相比，慢乙酰化表型个体的解毒能力降低。西班牙膀胱癌研究分析发现，在从不吸烟者中，慢乙酰化者相对于快速/中间乙酰化者的优势比（OR）为0.9，在曾经吸烟者中为1.6，吸烟者中的优势比增强了1.8倍。有证据表明乙酰化是一个依赖暴露的过程，因此相互作用的程度也可能取决于暴露水平。
我们扩展了一个用于吸烟超额优势比（EOR）的综合三参数线性指数模型，以纳入NAT2状态的影响，并重新分析膀胱癌数据中的吸烟和NAT2状态。
我们表明，吸烟风险随NAT2状态的变化是由与吸烟强度（每天吸烟支数）的相互作用引起的，而非总吸烟包年数。此外，NAT2慢乙酰化者吸烟风险的相对增加随吸烟强度增加。
分析揭示了NAT2慢乙酰化者中吸烟强度与膀胱癌之间的增强效应，且该效应随强度增加。
