Urinary levels of the tobacco-specific carcinogen N'-nitrosonornicotine and its glucuronide are strongly associated with esophageal cancer risk in smokers
Urinary levels of the tobacco-specific carcinogen N'-nitrosonornicotine and its glucuronide are strongly associated with esophageal cancer risk in smokers
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DOI：
10.1093/carcin/bgr125
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发表时间：
2011-09-01
期刊：
影响因子：
4.7
通讯作者：
Stepanov, Irina
中科院分区：
文献类型：
--
作者：
Yuan, Jian-Min;Knezevich, Aleksandar D.;Stepanov, Irina
N '-亚硝基去甲烟碱（NNN）和4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）是烟草特有的亚硝胺。NNN和NNK可以分别在实验室动物中诱发食管癌和肺癌，但缺乏人类食管癌的数据。NNN水平与4-从1986年至2008年，在中国上海的18244名中国男性队列中，对77名食管癌患者和223名单独匹配的对照者（均为当前吸烟者）在诊断和食管癌风险之前收集的尿液样本中的NNK代谢产物（甲基亚硝胺）-1-（3-吡啶基）-1-丁醇（NNAL）进行了检查。尿总NNN（游离NNN + NNN-N-葡糖苷酸）显著高于对照组，而其解毒产物NNN-N-葡糖苷酸的百分比显著低于对照组。在校正尿总NNAL和总可替宁以及吸烟强度和持续时间后，总NNN的第二和第三个三分位数与第一个三分位数相比，食管癌的比值比（95%置信区间）分别为3.99（1.25-12.7）和17.0（3.99-72.8）（P趋势< 0.001）。NNN-N-葡萄糖醛酸苷百分比的相应数值为0.37（0.17-0.80）和0.27（0.11-0.62）（P趋势= 0.001）。尿液总NNN和NNN-N-葡萄糖醛酸苷的百分比几乎完全解释了尿液总NNAL（游离NNAL加上其葡萄糖醛酸苷）、尿液总可替宁和吸烟强度与食道癌风险的相关性。这些发现沿着先前在实验室动物中的研究结果支持NNN在人类食管癌发生中的重要和独特作用。
N'-Nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are tobacco-specific nitrosamines. NNN and NNK can induce cancers of the esophagus and lung, respectively, in laboratory animals, but data on human esophageal cancer are lacking. The association between levels of NNN and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), an NNK metabolite, in urine samples collected before diagnosis and risk of esophageal cancer was examined in 77 patients with esophageal cancer and 223 individually matched controls, all current smokers, from a cohort of 18244 Chinese men in Shanghai, China, followed from 1986 to 2008. Urinary total NNN (free NNN plus NNN-N-glucuronide) was significantly higher, whereas the percentage of its detoxification product NNN-N-glucuronide was significantly lower in cases than controls. Odds ratios (95% confidence intervals) of esophageal cancer for the second and third tertiles of total NNN were 3.99 (1.25-12.7) and 17.0 (3.99-72.8), respectively, compared with the first tertile after adjustment for urinary total NNAL and total cotinine and smoking intensity and duration (P-trend < 0.001). The corresponding figures for the percentage of NNN-N-glucuronides were 0.37 (0.17-0.80) and 0.27 (0.11-0.62) (P-trend = 0.001). Urinary total NNN and the percentage of NNN-N-glucuronides almost completely accounted for the observed association for urinary total NNAL (free NNAL plus its glucuronides), urinary total cotinine and smoking intensity with esophageal cancer risk. These findings along with results of previous studies in laboratory animals support a significant and unique role of NNN in esophageal carcinogenesis in humans.