Background: It has been proven that the lung cancer mortality rate in Xuanwei County, China was among the highest in the country and has been associated with exposure to indoor smoky coal emissions that contain high levels of polycyclic aromatic hydrocarbons. This risk may be modified by variation in genetic polymorphisms and coal subtypes. Our objective was to use molecular epidemiological techniques to investigate the relationship among genetic polymorphisms, coal subtype and lung cancer risk in Xuanwei County.
Methods: On the basis of two population-based case-control studies in residents of Xuanwei County, China, questionnaires covering demographic information, smoking history, family and personal medical history, and information on other variables were administered and buccal cells and sputum samples were collected separately from each subject enrolled to extract DNA. GST superfamily, AKR1C3 superfamily, OGG1 superfamily and other genotype were scanned by useing PCR method. ORs and 95%CIs were used to estimate the association between genotypes, coal subtypes and lung cancer risk factors by conditional Logistic regression using Statistical Analysis Software.
Results: Compared with subjects who using smokeless coal or wood, smoky coal use was statistically significantly associated with lung cancer risk (OR=7.7, 95%CI: 4.5-13.3). There was marked heterogeneity in risk estimates for specific subtypes of smoky coal. Estimates were highest for coal from the Laibin (OR=24.8), Longtan (OR=11.6) and Baoshan (OR=6.0) coal types, and lower for coal from other types; the risk within the same subtype of coal in male and female were similar. The GSTM1-null genotype, the AKR1C3 (Ex1-70C>G), OGG1 (Ex6-315C>G) genotypes were closely associated with increased risk of lung cancer in Xuanwei County, and their odds ratios (95%CI) were 2.3 (1.3-4.2), 1.8 (1.0-3.5) and 1.9 (1.1-3.3), respectively. Compared to subjects who with GSTM1-positive and used less than 130 tons of smoky coal during their lifetime, higher risks were closely associated with GSTM1-null and heavier users (≥130 tons), with the OR was 4.9 (95%CI: 1.3-18.2) and 2.7 (95%CI: 1.0-7.4) for female and male, respectively. However, higher risks were only found within female for AKR1C3 (Ex1-70C>G) and OGG1 (Ex6-315C>G), with OR (95%CI)=12.9 (2.2-107.8) and 5.7 (1.1-34.2), respectively.
Conclusions: Lung cancer risks varied among coal subtypes; however, risks were similar between men and women exposed to the same type of coal. The GSTM1-null genotype may enhance susceptibility to air pollution from indoor smoky coal combustion emissions. AKR1C3 and OGG1 genotypes were significantly associated with higher risk of lung cancer, especially among heavily exposed women.
背景与目的 已有的研究证明：宣威是我国农村肺癌死亡率最高的地区，肺癌危险与室内燃烧烟煤产生的多环芳烃（polycyclic aromatic hydrocarbons, PAHs）有关，肺癌发病具有明显的地域性差别和家族聚集性。本研究从分子流行病学角度探索宣威肺癌风险的危险因素及与发病机理有关的基因型和燃煤类型。方法 运用两个基于人群的病例对照研究，开展问卷调查，同时采集口腔细胞和痰等生物样品，提取DNA。应用PCR法检测GST超家族、AKR超家族和OGG1等基因型。通过Logistic回归分析煤种、基因型与肺癌风险的关联。结果 与燃用无烟煤或木柴的研究对象相比，家用来宾烟煤的肺癌风险比数比（odds ratio, OR）值高达24.8，其次为龙潭（OR=11.6）、宝山（OR=6.0）、龙场（OR=4.1）、羊场（OR=3.8）等；燃用同种烟煤的男女肺癌风险相似。对于GSTM1缺失、AKR1C3（Ex1-70C>G）、OGG1（Ex6-315C>G）基因型，肺癌风险明显增高，且具统计学意义[OR（95%CI）分别为2.3（1.3-4.2）、1.8（1.0-3.5）和1.9（1.1-3.3）]。与家用烟煤量小且具GSTM1阳性的研究对象相比，用量大且GSTM1缺失的研究对象肺癌风险更高，女性OR为4.9（1.3-18.2），男性OR为2.7（1.0-7.4）。但对于AKR1C3（Ex1-70C>G）和OGG1（Ex6-315C>G），仅观察到女性肺癌风险的明显增高，OR分别为12.9（2.2-107.8）和5.7（1.1-34.2）。结论 宣威不同煤种的肺癌风险有很大差异，但暴露于相同煤种的男性与女性肺癌风险相似。GSTM1缺失基因型与肺癌风险增高有关联。AKR1C3与OGG1这2种基因型与肺癌风险有关联，且在烟煤使用量高的女性中肺癌风险更高。