Impact of smoking on lung cancer risk is stronger in those with the homozygous aldehyde dehydrogenase 2 null allele in a Japanese population
Impact of smoking on lung cancer risk is stronger in those with the homozygous aldehyde dehydrogenase 2 null allele in a Japanese population
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DOI：
10.1093/carcin/bgq021
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发表时间：
2010-04-01
期刊：
影响因子：
4.7
通讯作者：
Tanaka, Hideo
中科院分区：
文献类型：
--
作者：
Park, Ji Young;Matsuo, Keitaro;Tanaka, Hideo
乙醛暴露的主要生活方式是饮用酒精饮料，但烟草烟雾也有一定的贡献。虽然乙醛与上呼吸消化道癌症风险相关，但根据遗传决定的乙醛代谢，目前尚不清楚肺癌（一种代表性的吸烟相关癌症）是否与乙醛或影响其代谢的基因相关。我们进行了一项病例对照研究，以研究吸烟和乙醛脱氢酶2（ALDH 2）Glu 504 Lys多态性（rs671）之间可能的相互作用对肺癌的风险在日本。受试者为爱知癌症中心医院流行病学研究项目招募的718例肺癌病例和1416例非癌症对照。生活方式因素，包括吸烟，通过自填问卷确定。我们采用包年（PY;分为五个级别：从不，< 15，< 30，< 45 and >= 45）作为累积吸烟暴露的标志。吸烟、ALDH 2基因型及其相互作用对肺癌风险的影响通过比值比（OR）和校正潜在混杂因素的95%置信区间进行评估。在< 45 and >Glu/Glu或Glu/Lys患者中，PY < 15、< 30、= 45相对于从不吸烟者的校正OR分别为1.39、1.80、3.44和6.25（P趋势= 1.4 x 10（-30））。相比之下，Lys/Lys的OR分别为1.01、10.2、11.4和23.2（P趋势= 2.6 x 10（-7））。ALDH 2基因型（Glu/Glu + Glu/Lys vs Lys/Lys）与累积吸烟剂量之间的相互作用具有统计学显著性（P = 0.036），并且在从不饮酒者的分析中始终观察到（相互作用P = 0.041）。这些结果表明，ALDH 2赖氨酸/赖氨酸，一个空酶活性基因型，修改吸烟对肺癌风险的影响。
The main lifestyle contributor to acetaldehyde exposure is the drinking of alcoholic beverages, but tobacco smoke also makes some contribution. Although acetaldehyde is associated with upper aerodigestive tract cancer risk, in accordance with genetically determined acetaldehyde metabolism, it is unclear whether lung cancer, a representative smoking-related cancer, is associated with acetaldehyde or genes impacting its metabolism. We conducted a case-control study to examine possible interaction between smoking and aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism (rs671) on the risk of lung cancer in Japanese. Subjects were 718 lung cancer cases and 1416 non-cancer controls enrolled in the Hospital-based Epidemiologic Research Program at Aichi Cancer Center. Lifestyle factors, including smoking, were determined by self-administered questionnaire. We applied pack-years (PY; categorized into five levels: never, < 15, < 30, < 45 and >= 45) as a marker of cumulative exposure to smoking. The impact of smoking, ALDH2 genotype, and their interaction on lung cancer risk were assessed by odds ratio (OR) and 95% confidence interval adjusted for potential confounders. Adjusted ORs for PY < 15, < 30, < 45 and >= 45 relative to never smokers among those with Glu/Glu or Glu/Lys were 1.39, 1.80, 3.44 and 6.25, respectively (P-trend = 1.4 x 10(-30)). In contrast, ORs among Lys/Lys were 1.01, 10.2, 11.4 and 23.2, respectively (P-trend = 2.6 x 10(-7)). Interaction between ALDH2 genotype (Glu/Glu + Glu/Lys versus Lys/Lys) and cumulative smoking dose was statistically significant (P = 0.036) and was consistently observed in the analysis among never-drinkers (interaction P = 0.041). These results suggest that ALDH2 Lys/Lys, a null enzyme activity genotype, modifies the impact of smoking on the risk of lung cancer.