谷胱甘肽S-转移酶μ1和N-乙酰转移酶2基因多态性与非吸烟和吸烟肺癌患者及人群对照中烟草烟雾暴露的关系

Glutathione S-transferase mu1 and N-acetyltransferase 2 genetic polymorphisms and exposure to tobacco smoke in nonsmoking and smoking lung cancer patients and population controls.

作者信息

Nyberg F, Hou S M, Hemminki K, Lambert B, Pershagen G

机构信息

Division of Environmental Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.

出版信息

Cancer Epidemiol Biomarkers Prev. 1998 Oct;7(10):875-83.

DOI:

PMID:9796632

Abstract

We conducted a case-control study to assess the risk of lung cancer in relation to genetic polymorphisms of the detoxifying enzymes glutathione-S-transferase mu1 (GSTM1) and N-acetyl transferase 2 (NAT2), focusing on never-smokers, women, and older people. The study base consisted of persons > or =30 years of age in Stockholm County from 1992 to 1995. We recruited never-smoking lung cancer cases and a sex- and age-matched sample of ever-smoking cases at the three county hospitals mainly responsible for diagnosing and treating lung cancer. A total of 185 cases (25.4% men; 47.6% never-smokers) and 164 frequency-matched population controls (28.7% men; 48.2% never-smokers) supplied blood for genotyping. Detailed information was collected by interview on active and passive smoking, occupations, residences, and diet. The overall odds ratio (OR) for lung cancer associated with the GSTM1 null (GSTM1-) versus GSTM1+ genotype was 0.8 [95% confidence interval (CI), 0.5-1.2], with an OR close to unity among smokers, and lower ORs suggested among never-smokers. For NAT2 slow versus rapid acetylator genotypes, the OR was 1.0 (95% CI, 0.6-1.5) overall, which broke down into an increased risk for slow acetylators among never-smokers but an increased risk for rapid acetylators among smokers. Among never-smokers, a gene interaction was suggested, with combined slow acetylator and GSTM1+ genotype conferring particularly high risk (OR = 3.1; 95% CI, 1.1-8.6), but no clear pattern emerged among smokers. A detailed analysis among smokers showed no interaction between pack-years of smoking and the GSTM1 genotype but suggested a steeper increase in risk with increasing pack-years of smoking exposure for rapid than for slow acetylators. Our results do not support a major role for the GSTM1 genetic polymorphism as a risk factor for lung cancer among smokers or nonsmokers. There was, however, some suggestion that the slow acetylator genotype may confer an increased risk among never-smokers and that the rapid acetylator genotype interacts with pack-year dose to produce a steeper risk gradient among smokers.

摘要

我们开展了一项病例对照研究，以评估解毒酶谷胱甘肽-S-转移酶μ1（GSTM1）和N-乙酰转移酶2（NAT2）的基因多态性与肺癌风险之间的关系，重点关注从不吸烟者、女性和老年人。研究对象为1992年至1995年斯德哥尔摩县年龄≥30岁的人群。我们在主要负责诊断和治疗肺癌的三家县医院招募了从不吸烟的肺癌病例以及性别和年龄匹配的曾经吸烟病例样本。共有185例病例（25.4%为男性；47.6%为从不吸烟者）和164例频率匹配的人群对照（28.7%为男性；48.2%为从不吸烟者）提供血液用于基因分型。通过访谈收集了关于主动和被动吸烟、职业、住所及饮食的详细信息。与GSTM1基因缺失（GSTM1-）相比，GSTM1+基因型与肺癌相关的总体优势比（OR）为0.8[95%置信区间（CI），0.5 - 1.2]，在吸烟者中OR接近1，而在从不吸烟者中OR较低。对于NAT2慢乙酰化基因型与快乙酰化基因型，总体OR为1.0（95%CI，0.6 - 1.5），在从不吸烟者中慢乙酰化者风险增加，而在吸烟者中快乙酰化者风险增加。在从不吸烟者中，提示存在基因相互作用，慢乙酰化基因型与GSTM1+基因型组合的风险特别高（OR = 3.1；95%CI，1.1 - 8.6），但在吸烟者中未出现明确模式。对吸烟者的详细分析显示，吸烟包年数与GSTM1基因型之间无相互作用，但提示快乙酰化者随着吸烟包年数增加风险上升幅度比慢乙酰化者更大。我们的结果不支持GSTM1基因多态性在吸烟者或非吸烟者中作为肺癌风险因素起主要作用。然而，有一些迹象表明，慢乙酰化基因型可能使从不吸烟者的风险增加，并且快乙酰化基因型与吸烟包年剂量相互作用，在吸烟者中产生更陡峭的风险梯度。