Urinary levels of tobacco-specific nitrosamine metabolites in relation to lung cancer development in two prospective cohorts of cigarette smokers.
Urinary levels of tobacco-specific nitrosamine metabolites in relation to lung cancer development in two prospective cohorts of cigarette smokers.
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DOI：
10.1158/0008-5472.can-08-4330
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发表时间：
2009-04-01
期刊：
影响因子：
11.2
通讯作者：
Hecht SS
中科院分区：
文献类型：
--
作者：
Yuan JM;Koh WP;Murphy SE;Fan Y;Wang R;Carmella SG;Han S;Wickham K;Gao YT;Yu MC;Hecht SS
4-(甲基亚硝基氨基)-1-(3-吡啶基)-1-丁醇 (NNAL) 及其葡萄糖醛酸苷（其总和表示为总 NNAL）是 4-(甲基亚硝基氨基)-1-(3-吡啶基)-1-丁酮 (NNK) 的代谢物。 NNK 和 NNAL 可在实验动物中诱导肺癌，但人类数据有限。在两个中国吸烟者前瞻性队列中评估了尿总 NNAL 的诊断前水平与肺癌发生风险之间的关联。我们进行了一项巢式病例对照研究，涉及 246 例肺癌病例和 245 例队列对照，这些对照按年龄、性别、队列入组时居住的社区和尿液收集日期与指示病例进行单独匹配。尿液中总 NNAL 水平与肺癌风险呈剂量依赖性显着相关。相对于最低三分位数，在调整自我报告的吸烟史和尿总可替宁后，与总 NNAL 的第二和第三三分位数相关的风险分别为 1.43 (95% CI 0.86-2.37) 和 2.11 (95% CI 1.25-3.54)（趋势 P =0.005）。与吸烟史相当但尿液总 NNAL 和总可替宁含量最低的吸烟者相比，尿液总 NNAL 和总可替宁含量最高的吸烟者患肺癌的风险增加了 8.5 倍（95% CI 3.7-19.5）。本研究的结果将 NNK 暴露与人类肺癌的发展直接联系起来。
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (sum of which is denoted as total NNAL) are metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). NNK and NNAL can induce lung cancer in laboratory animals but human data are limited. The association between pre-diagnostic levels of urinary total NNAL and risk of lung cancer development was evaluated in two prospective cohorts of Chinese cigarette smokers. We conducted a nested case-control study involving 246 cases of incident lung cancer and 245 cohort controls who were individually matched to the index cases by age, gender, neighborhood of residence at cohort enrollment, and date of urine collection. Urinary levels of total NNAL were significantly associated with risk of lung cancer in a dose-dependent manner. Relative to the lowest tertile, risks associated with the 2nd and 3rd tertiles of total NNAL were 1.43 (95% CI 0.86-2.37) and 2.11 (95% CI 1.25-3.54), respectively (P for trend =0.005) after adjustment for self-reported smoking history and urinary total cotinine. Smokers in the highest tertiles of urinary total NNAL and total cotinine exhibited a 8.5-fold (95% CI 3.7-19.5) increased risk for lung cancer relative to smokers with comparable smoking history but possessing the lowest tertiles of urinary total NNAL and total cotinine. Findings of the present study directly link NNK exposure to lung cancer development in humans.