Metabolites of the Polycyclic Aromatic Hydrocarbon Phenanthrene in the Urine of Cigarette Smokers from Five Ethnic Groups with Differing Risks for Lung Cancer

Results from the Multiethnic Cohort Study demonstrated significant differences in lung cancer risk among cigarette smokers from five different ethnic/racial groups. For the same number of cigarettes smoked, and particularly among light smokers, African Americans and Native Hawaiians had the highest risk for lung cancer, Whites had intermediate risk, while Latinos and Japanese Americans had the lowest risk. We analyzed urine samples from 331–709 participants from each ethnic group in this study for metabolites of phenanthrene, a surrogate for carcinogenic polycyclic aromatic hydrocarbon exposure. Consistent with their lung cancer risk and our previous studies of several other carcinogens and toxicants of cigarette smoke, African Americans had significantly (pGSTT1 explained 2.2% of the variability in PheT, while the strongest association, rs5751777 (p = 1.8x10-62) in the GSTT2 gene, explained 7.7% of the variability in PheT. These GWAS results suggested a possible protective effect of lower GSTT1 copy number variants on the diol epoxide pathway, which was an unexpected result. Collectively, the results of this study provide further evidence that different patterns of cigarette smoking are responsible for the higher lung cancer risk of African Americans than of Whites and the lower lung cancer risk of Japanese Americans, while other factors appear to be involved in the differing risks of Native Hawaiians and Latinos.多民族队列研究（Multiethnic Cohort Study）的结果显示，来自5个不同种族/族群的吸烟者在肺癌发病风险上存在显著差异。在吸烟量相同的前提下，尤其是轻度吸烟者群体中，非裔美国人与夏威夷原住民的肺癌发病风险最高，白人处于中等风险水平，而拉丁裔与日裔美国人的肺癌风险最低。本研究针对该队列中每个族群的331至709名参与者的尿液样本展开分析，检测了菲（phenanthrene）的代谢产物——该代谢物可作为香烟烟雾中致癌性多环芳烃（polycyclic aromatic hydrocarbon）暴露的替代标志物。结合非裔美国人的肺癌风险特征与我们此前针对香烟烟雾中多种其他致癌物与有毒物质的研究结果，非裔美国人的相关代谢物水平存在显著差异，且谷胱甘肽S-转移酶θ1（GSTT1）可解释PheT 2.2%的变异度；而位于GSTT2（谷胱甘肽S-转移酶θ2）基因上的最强关联位点rs5751777（p=1.8×10^-62）则可解释7.7%的PheT变异度。这些全基因组关联研究（GWAS, Genome-Wide Association Study）结果提示，GSTT1低拷贝数变异可能对二醇环氧化物通路具有保护作用，这一结果出乎我们的意料。综上，本研究结果进一步证实，吸烟模式的差异是导致非裔美国人肺癌风险高于白人、日裔美国人肺癌风险低于白人的关键因素；而夏威夷原住民与拉丁裔的风险差异则可能与其他因素相关。