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[宣威分子流行病学研究:煤种、基因类型与肺癌风险之间的关系]

[Molecular epidemiology study in Xuanwei: the relationship among 
coal type, genotype and lung cancer risk].

作者信息

Li Jihua, He Jun, Tang Rui, Hu Wei, Lan Qing, He Xingzhou, Li Yun, Zhang Yunsheng

机构信息

Qujing Centers for Disease Control and Prevention, Qujing 655000, China.

Qujing Municipal Bureau of Health, Qujing 655000, China.

出版信息

Zhongguo Fei Ai Za Zhi. 2015 Jan;18(1):16-22. doi: 10.3779/j.issn.1009-3419.2015.01.03.

Abstract

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.

摘要

背景

事实证明,中国宣威县的肺癌死亡率位居全国前列,且与接触含有高浓度多环芳烃的室内烟煤排放物有关。这种风险可能会因基因多态性和煤的亚型差异而有所改变。我们的目标是运用分子流行病学技术,研究宣威县基因多态性、煤的亚型与肺癌风险之间的关系。

方法

基于在中国宣威县居民中开展的两项基于人群的病例对照研究,发放涵盖人口统计学信息、吸烟史、家族和个人病史以及其他变量信息的问卷,并从每位纳入研究的受试者处分别采集颊细胞和痰液样本以提取DNA。采用PCR方法对谷胱甘肽S-转移酶(GST)超家族、醛酮还原酶1C3(AKR1C3)超家族、8-氧鸟嘌呤DNA糖基化酶1(OGG1)超家族及其他基因型进行检测。运用统计分析软件,通过条件Logistic回归,采用比值比(OR)和95%可信区间(CI)来评估基因型、煤的亚型与肺癌风险因素之间的关联。

结果

与使用无烟煤或木材的受试者相比,使用烟煤与肺癌风险在统计学上具有显著相关性(OR = 7.7,95%CI:4.5 - 13.3)。烟煤特定亚型的风险估计存在显著异质性。来自来宾(OR = 24.8)、龙潭(OR = 11.6)和宝山(OR = 6.0)煤种的煤风险估计最高,其他煤种的风险较低;同一煤亚型内男性和女性的风险相似。GSTM1基因缺失型、AKR1C3(Ex1 - 70C>G)、OGG1(Ex6 - 315C>G)基因型与宣威县肺癌风险增加密切相关,其比值比(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GSTM1基因阳性且一生中使用烟煤少于130吨的受试者相比,GSTM1基因缺失型且使用量较大(≥130吨)的使用者风险更高,女性和男性的OR分别为4.9(95%CI:1.3 - 18.2)和2.7(95%CI:1.0 - 7.4)。然而,仅在女性中发现AKR1C3(Ex1 - 70C>G)和OGG1(Ex6 - 315C>G)的风险较高,其OR(95%CI)分别为12.9(2.2 - 107.8)和5.7(1.1 - 34.2)。

结论

肺癌风险在煤的亚型之间存在差异;然而,接触同一类型煤的男性和女性风险相似。GSTM1基因缺失型可能会增强对室内烟煤燃烧排放空气污染的易感性。AKR1C3和OGG1基因型与较高的肺癌风险显著相关,尤其是在接触程度较高的女性中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddd2/5999738/74c29097800c/zgfazz-18-1-16-1.jpg

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