Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Via Giacomo Venezian 1, 20133 Milan, Italy.
Carcinogenesis. 2010 Mar;31(3):331-3. doi: 10.1093/carcin/bgp282. Epub 2009 Nov 12.
The nicotinic 15q25 locus has been implicated in lung cancer risk, with an odds ratio of approximately 1.3. The same locus is associated with nicotine dependence due to cigarette smoking and with smoking-associated chronic obstructive pulmonary disease, which is a risk factor for lung cancer. Our meta-analysis of reported studies shows that this locus was not associated with lung cancer risk in >1000 never-smoker cases and >1800 controls. Review of exposure-response data for lung cancer risk showed that less than a half-cigarette per day may confer the same risk of lung cancer as that conferred by the 15q25 locus. Given the lack of effect in never-smokers and the known common and variable underreporting of smoking habit in studies on smoking-associated diseases, we cannot exclude that the association between the 15q25 locus and lung cancer risk is indirect, deriving from association of the same locus with smoking habit. Since nicotine is not carcinogenic, available data do not provide plausibility of the association between the nicotinic 15q25 locus and lung cancer pathogenesis. Thus, a direct link between the 15q25 locus and lung cancer risk has yet to be established.
烟碱 15q25 基因座与肺癌风险相关，其比值比约为 1.3。同一基因座与吸烟引起的尼古丁依赖以及与吸烟相关的慢性阻塞性肺疾病相关，后者是肺癌的一个风险因素。我们对已报道的研究进行的荟萃分析表明，该基因座与 >1000 例从不吸烟者和 >1800 例对照者的肺癌风险无关。对肺癌风险的暴露-反应数据的审查表明，每天吸不到半支烟与 15q25 基因座赋予的肺癌风险相同。鉴于从不吸烟者中没有影响，以及已知在与吸烟相关的疾病的研究中吸烟习惯的常见和可变漏报，我们不能排除 15q25 基因座与肺癌风险之间的关联是间接的，源自同一基因座与吸烟习惯的关联。由于尼古丁没有致癌性，因此现有数据并不能提供烟碱 15q25 基因座与肺癌发病机制之间关联的合理性。因此，15q25 基因座与肺癌风险之间的直接联系尚未建立。
