Smoky Coal Research Articles

Abstract 1876: Assessment of exposure to potential lung carcinogens in Xuanwei and Fuyuan, China: Particulate exposure from cooking and heating stoves

Abstract Residents in Xuanwei, China have the highest lung cancer incidence rates in China for both men and women, despite the fact that almost all women are non-smokers. Several lines of research have provided strong support that the excess lung cancer rate in this region is caused primarily by emissions from smoky coal exposure. We have carried out a hospital-based case-control study of non-smoking female lung cancer in Xuanwei and its neighboring county, Fuyuan, to identify which constituents of coal combustion emissions and other indoor environmental exposures are causing the high lung cancer rates in this region. In order to develop individual estimates of exposure to known or suspected lung carcinogens, we designed a comprehensive exposure assessment study of 163 households in this region to evaluate exposure to PAHs, PM2.5, silica, and other exposures from coal and wood burning. Homes that used three main fuel types (i.e., smoky coal, smokeless coal and wood), and eight stove types [e.g., firepit, fixed or portable stove, with or without ventilation] were identified and households were sampled on two consecutive days. Up to 30 households were selected for each combination of fuel and stove type. A subgroup of 53 households was measured at two time-points during the study year (e.g. summer and winter). The female head of each household was asked to wear a 24-hour personal PM2.5 air sampler at the same time that 24-hour area air sampling was employed in the main living area. Personal and area particulate matter samples (PM2.5) were collected in each home. These samples were also used to quantify particle bound PAHs including BaP (by GC/MS), elemental components (by XRF and ICP/MS), and silica (by XRD). XAD2 samples were collected for the quantification of gaseous PAHs. Other samples, including radon and organic vapor, fuel and ash were also obtained. We also collected information on potential factors that could influence exposure, such as house characteristics, stove type, fuel type and use, amount of fuel used, amount of time spent in each room. Initial analyses show that people using wood burned in firepits were exposed to the highest levels of PM2.5 measured in area (536.3±370.5 µg/m3) and personal samples(419.8±283.3 µg/m3). Burning smokeless coal in a high stove with a chimney was associated with the lowest exposure to PM2.5 (62.2±34.1 µg/m3, 62.5±29.9 µg/m3 for area and personal samples, respectively). These data show that there is a wide range of exposure to PM2.5 in this population. These data and other exposure information from this study will be used in the future to model environmental exposures and risk of lung cancer in this special, high risk population. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1876. doi:10.1158/1538-7445.AM2011-1876

Commentary: Abating climate change and lung cancer!

The systematic review of Hosgood et al. published in this issue of the IJE, provides strong and sobering evidence about the price several hundred million people, mostly in Asia, pay for cooking or heating with coal using unvented stoves: a 2to 5-fold increased risk of developing lung cancer. The focus on geographic differences in the risks highlight that some areas in China are particularly strongly affected; be it due to different compositions of coal or habits and exposure patterns. The majority of the 25 studies come from China where the use of coal remains highly prevalent. Primary energy sources in China— the world’s biggest emitter of CO2—are strongly dominated by coal (470%). Lung cancer is just the tip of the iceberg of the adverse effects of indoor coal (and biomass) combustion. Lung cancer and chronic respiratory diseases, in particular chronic obstructive pulmonary disease (COPD), not only cluster among smokers, but also among those exposed to indoor air pollution due to coal or biomass combustion. Due to its chronic long-term nature, the morbidity burden related to COPD largely exceeds that due to lung cancer although mortality rates are rather similar for both diseases. The two diseases not only share pathological pathways, but COPD increases the risk of developing lung cancer four to five times. A previous cohort study from China showed that the lung cancer risk due to indoor coal combustion was even larger than the risk related to tobacco smoking: women with a history of 440 years of cooking had a 43-fold lung cancer incidence compared with those cooking <20 years, while men with 440 years smoking history had a 50% higher lung cancer incidence compared with those with <20 years of smoking. The question arises how to abate this entirely preventable burden of morbidity and mortality caused by indoor coal combustion. As shown in the above mentioned retrospective cohort study, stove improvement programmes in the rural Xuanwei region of China effectively cut lung cancer incidence by half. The intervention in this cohort study consisted in the change from smoky coal fires to stoves with chimneys. While this is promising, the approach falls short in embracing the problem in a more holistic manner. Two issues are of particular relevance. First, chimneys simply transport the combustionrelated pollution to the outdoor environment. While concentrations of health-relevant toxicants are certainly far more diluted outdoors than in poorly vented rooms, outdoor air pollution remains an environmental hazard shared among the entire population, day and night. Ambient air pollution contributes to a range of health problems including lung cancer. In fact, the impact of the indoor coal combustion is even underestimated in the studies reviewed by Hosgood et al., as cancer rates due to coal-related outdoor pollution (from indoor origin) contribute to the ‘background rates’ of lung cancer, thus diluting the relative risks due to indoor combustion of coal. Depending on local conditions and topography, indoor combustion can indeed become the dominant cause of outdoor air pollution. This is exemplified in the Mongolian capital Ulaan-Baatar, where poorquality stoves and boilers fuelled by coal and wood have become the single most important cause of a permanent ‘outdoor air quality crisis’, with daily mean particulate matter concentrations regularly exceeding 1000 mg/m. Secondly, coal ranks very high both in terms of equivalent CO2 emissions (per energy content) and of air pollution-related health effects. From a climate change perspective, coal combustion—indoors as well as in power plants or industries—remains a main problem and challenge. Most attractive are policy decisions that promote win–win situations in both abating climate change and improving the environment (air quality in this case) to maximize the public-health benefits. As shown in a comparative risk assessment scenario conducted for India, replacing 150 million combustionbased stoves with electric ones could avoid 12 500 disability-adjusted life years (DALYs) per million person-years while saving some 0.2 Mt of CO2 Published by Oxford University Press on behalf of the International Epidemiological Association

Descriptive study on the epidemiology of lung cancer in coal-producing area in eastern Yunnan, China

背景与目的云南省宣威市位于滇东黔西晚二叠纪聚煤区，当地肺癌死亡率居全国首位，研究显示宣威农民肺癌高发与室内烟煤燃烧产生的多环芳烃等污染物有关。近年来宣威周边产煤地区环境污染和肺癌高发问题引起国内外关注，滇东其它地区居民肺癌流行水平与发病原因是否与宣威相似未见报道。本研究旨在探索滇东产（燃）煤地区农民肺癌流行状况和发病原因。方法采用多阶段、分层、整群、概率抽样方法随机抽取滇东产（燃）煤382个调查小区，对其中30岁-79岁常住居民进行X线胸片肺癌筛查和相关因素调查，筛查阳性疑似肺癌进行CT复查，诊断为肺癌的病例进行痰癌细胞检查和随访。采用世界肿瘤研究中心标化率比对不同地区肺癌筛查阳性率进行显著性检验分析、调整合并为A区、B区、C区、D区等4层，并进行肺癌相关因素分析。结果共筛查和问卷调查52, 833名农村居民，X线胸片筛查疑似肺癌阳性604例，541例经过CT复查，诊断为肺癌363例（其中组织学确诊109例），CT复查校正筛查阳性率763.08/10万，世界人口标化率426.28/10万（95%CI：381.51/10万-471.05/10万), 男性482.78/10万，女性387.98/10万，男女比值1.24。各层肺癌流行强度差别较大，从A区→B区→C区→D区，肺癌筛查世标率逐渐减少，男女比值逐渐增大。筛查世标率最高的A区是最低D区的6.97倍。肺癌筛查阳性率与煤炭资源分布有关，调查对象肺癌筛查阳性率与烟煤使用率和使用量成正比，而与无烟煤使用率和使用量无明显关联。调查地区居民早期火塘使用率80%以上，其下无进气口，上无烟囱，煤炭燃烧不完全，加重煤烟废气污染。家族成员肺癌死亡率与肺癌筛查阳性率的分布一致，肺癌筛查阳性率随家族成员肺癌死亡率增加而增加。男性吸烟率85.08%，平均吸烟量16.12支/天；约50%从事过采煤、炼焦等工作。女性吸烟率1.37%，主要从事农业生产和做饭、喂养生猪等室内家务工作，吸烟、职业危害不是女性肺癌的主要发病因素，但可能是男性肺癌发病比女性严重的影响因素。结论肺癌高发与室内外烟煤污染、家族易感性有关联，吸烟、采煤、炼焦不是女性肺癌的主要因素。

Primary investigation of the pollution status of polycyclic aromatic hydrocarbons (PAHs) in water and soil of Xuanwei and Fuyuan, Yunnan Province, China

Lung cancer incidence in Xuanwei and Fuyuan is extremely high. The air pollution, especially indoor airborne PAHs generated by burning smoky coals, has been considered as the most probable reason. The air pollution may affect drinking water and soil through dry and wet deposition. In this study, the concentrations of PAHs in water and soil samples from Xuanwei and Fuyuan were monitored to investigate the influence of atmospheric PAHs pollution on water and soil. No obvious PAHs pollution in water was found in these two areas, indicating that airborne PAHs have no apparent effect on the drinking water (well water). The smoky coal combustion from household and industry, such as the activities related to power plants, coking plants and chemical industries, is responsible for the soil PAHs pollution in these two areas. The soil pollution might be the reemission source and would pose long-term threat to the local environment and health of residents.

Polymorphisms in innate immunity genes and lung cancer risk in Xuanwei, China

The high incidence of lung cancer in Xuanwei County, China has been attributed to exposure to indoor smoky coal emissions that contain polycyclic aromatic hydrocarbons (PAHs). The inflammatory response induced by coal smoke components may promote lung tumor development. We studied the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and lung cancer risk in a population-based case-control study (122 cases and 122 controls) in Xuanwei. A total of 1,360 tag SNPs in 149 gene regions were included in the analysis. FCER2 rs7249320 was the most significant SNP (OR: 0.30; 95% CI: 0.16-0.55; P: 0.0001; false discovery rate value, 0.13) for variant carriers. The gene regions ALOX12B/ALOX15B and KLK2 were associated with increased lung cancer risk globally (false discovery rate value <0.15). In addition, there were positive interactions between KLK15 rs3745523 and smoky coal use (OR: 9.40; P-interaction = 0.07) and between FCER2 rs7249320 and KLK2 rs2739476 (OR: 10.77; P-interaction = 0.003). Our results suggest that genetic polymorphisms in innate immunity genes may play a role in the genesis of lung cancer caused by PAH-containing coal smoke. Integrin/receptor and complement pathways as well as IgE regulation are particularly noteworthy.

Tuberculosis and subsequent risk of lung cancer in Xuanwei, China

Tobacco and indoor air pollution from smoky coal are major causes of lung cancer in rural Xuanwei County, China. Tuberculosis has been suggested to increase lung cancer risk, but data from prior studies are limited. We conducted an analysis of data from a retrospective cohort study of 42,422 farmers in Xuanwei. In 1992, interviewers administered a standardized questionnaire that included lifetime medical history, including tuberculosis. Subjects were followed from 1976, with deaths from lung cancer ascertained through 1996. We used proportional hazards regression to assess the association between tuberculosis and subsequent lung cancer mortality. Tuberculosis was reported by 246 subjects (0.6%), and 2,459 (5.8%) died from lung cancer during follow-up. Lung cancer mortality was substantially higher in subjects with tuberculosis than in those without (25 vs. 3.1 per 1,000 person-years). The association was especially pronounced in the first 5 years after tuberculosis diagnosis (hazard ratios [HRs] ranging 6.7-13) but remained strong 5-9.9 years (HR 3.4, 95% CI 1.3-9.1) and 10+ years (HR 3.0, 95% CI 1.3-7.3) after tuberculosis. These associations were similar among men and women and among smoky coal users (70.5% of subjects). Adjustment for demographic characteristics, lung disease and tobacco use did not affect results. In Xuanwei, China, tuberculosis is an important risk factor for lung cancer. The increased lung cancer risk, persisting years after a tuberculosis diagnosis, could reflect the effects of chronic pulmonary inflammation and scarring arising from tuberculosis.

Portable stove use is associated with lower lung cancer mortality risk in lifetime smoky coal users

Domestic fuel combustion from cooking and heating, to which about 3 billion people worldwide are exposed, is associated with increased lung cancer risk. Lung cancer incidence in Xuanwei is the highest in China, and the attributable risk of lung cancer from unvented smoky coal burning is greater than 90%. To evaluate any lung cancer mortality reduction after changing from unvented stoves to portable stoves, we used lifetime smoky coal users in a retrospective cohort of all farmers born during 1917–1951 and residing in Xuanwei in 1976. Of the 42 422 enrolled farmers, 4054 lifetime smoky coal users changed to portable stoves, 4364 did not change, and 1074 died of lung cancer. Lung cancer morality associated with stove change was assessed by product-limit survival curves and multivariate Cox regression models. Both men (P<0.0001) and women (P<0.0001) who changed to portable stoves had a significantly increased probability of survival compared with those who did not change. Portable stoves were associated with decreased risk of lung cancer mortality in male participants (hazard ratio (HR)=0.62, 95% confidence interval (CI)=0.46–0.82) and female participants (HR=0.41, 95% CI=0.29–0.57). Portable stove use is associated with reduced lung cancer mortality risk, highlighting a cost-effective intervention that could substantially benefit health in developing countries.

Coal Use, Stove Improvement, and Adult Pneumonia Mortality in Xuanwei, China: A Retrospective Cohort Study

BackgroundIn Xuanwei County, China, unvented indoor coal burning is strongly associated with increased risk of lung cancer and chronic obstructive pulmonary disease. However, the impact of coal burning and stove improvement on risk of pneumonia is not clear.MethodsWe conducted a retrospective cohort study among all farmers born 1917 through 1951 and living in Xuanwei as of 1 January 1976. The analysis included a total of 42,422 cohort members. Follow-up identified all deaths in the cohort from 1976 through 1996. Ages at entry into and at exit from follow-up ranged from 24 to 59 years and from 25 to 80 years, respectively. The record search detected 225 deaths from pneumonia, and 32,332 (76%) were alive as of 31 December 1996. We constructed multivariable Cox models (time variable = age) to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsUse of coal, especially smokeless coal, was positively associated with pneumonia mortality. Annual tonnage and lifetime duration of smoky and smokeless coal use were positively associated with pneumonia mortality. Stove improvement was associated with a 50% reduction in pneumonia deaths (smoky coal users: HR, 0.521; 95% CI, 0.340–0.798; smokeless coal users: HR, 0.449; 95% CI, 0.215–0.937).ConclusionsOur analysis is the first to suggest that indoor air pollution from unvented coal burning is an important risk factor for pneumonia death in adults and that improving ventilation by installing a chimney is an effective measure to decrease it.

Variation in lung cancer risk by smoky coal subtype in Xuanwei, China

Lung cancer rates in Xuanwei County have been among the highest in China for both males and females and have been causally associated with exposure to indoor smoky (bituminous) coal emissions that contain very high levels of polycyclic aromatic hydrocarbons. There are numerous coal mines across the County. Although lung cancer risk is strongly associated with the use of smoky coal as a whole, variation in risk by smoky coal subtype has not been characterized as yet. We conducted a population-based case-control study of 498 lung cancer cases and 498 controls, individually matched to case subjects on age (+/-2 years) and sex to examine risk by coal subtype. Odds ratios (ORs) and 95% confidence intervals (CIs) for coal subtype were calculated by conditional logistic regression, adjusting for potential confounders. Overall, smoky coal use was positively and statistically significantly associated with lung cancer risk, when compared with the use of smokeless coal or wood (OR = 7.7, 95% CI = 4.5-13.3). Furthermore, there was a marked heterogeneity in risk estimates for specific subtypes of smoky coal (test for heterogeneity: p = 5.17 x 10(-10)). Estimates were highest for coal of the Laibin (OR = 24.8, 95% CI = 12.4-49.6) and Longtan (OR = 11.6, 95% CI = 5.0-27.2) coal types and lower for coal from other subtypes. These findings strongly suggest that in Xuanwei and elsewhere, the carcinogenic potential of coal combustion products can exhibit substantial local variation by specific coal source.

Mitochondrial DNA content and lung cancer risk in Xuan Wei, China

Smoky coal contains polycyclic aromatic hydrocarbons (PAHs) and has been strongly implicated in etiology of lung cancer in Xuan Wei, China. While PAHs form bulky adducts in nuclear DNA, they have a 40–90-fold greater affinity for mitochondrial DNA (mtDNA). mtDNA content may increase to compensate for mtDNA damage. We conducted a population-based case–control study of lung cancer in Xuan Wei, China hypothesizing that mtDNA content is positively associated with lung cancer risk. Cases ( n = 122) and controls ( n = 121) were individually matched on age (±2 years), sex, village of residence, and current fuel type. Lifetime smoky coal use and potential confounders were determined with questionnaires. mtDNA was extracted from sputum and mtDNA content was determined with quantitative PCR. ORs and 95% CIs were calculated with unconditional logistic regression. mtDNA content >157 copies per cell was associated with lung cancer risk (OR = 1.8; 95% CI = 1.0–3.2) compared with those with ≤157 copies. In summary, mtDNA content was positively associated with lung cancer risk. Furthermore, mtDNA content was more strongly associated with lung cancer risk among older individuals. However, due to the small sample size, additional studies are needed to evaluate this potential association.

Dietary factors, food contamination and lung cancer risk in Xuanwei, China

In rural Xuanwei County, China, the high incidence of lung cancer is attributable largely to burning smoky coal indoors for heating and cooking without adequate ventilation. Such burning generates very high levels of indoor air pollutants, including carcinogenic polycyclic aromatic hydrocarbons, which could contaminate foodstuffs in the home. Thus, residents could be exposed to carcinogenic coal emissions not only via inhalation but also via ingestion of these foodstuffs. A population-based case-control study of 498 lung cancer patients and 498 controls was conducted from 1985 through 1990 in Xuanwei. The interviewer-administered study questionnaire queried the frequency of food items commonly consumed in this region. Overall and sex-specific multiple logistic regression models were constructed to estimate Odds ratios (OR) and 95% confidence intervals (CI) for consumption of these foods. Intake of rice, green vegetables, mushrooms and fresh meat was associated with an increased risk of lung cancer. In contrast, intake of corn, buckwheat, radishes, peppers, melons, pickled vegetables, and salt-preserved meats was associated with reduced risk. The detrimental effect of ingesting green vegetables (OR, 2.39; 95% CI, 1.28-4.48) is consistent with previous reports. These findings suggest that in Xuanwei, food contamination by environmental polycyclic aromatic hydrocarbons may be an important risk factor for lung cancer, and that differential contamination of foods by polycyclic aromatic hydrocarbons possibly explained the different associations with lung cancer risk.

A report of cytokine polymorphisms and COPD risk in Xuan Wei, China

Indoor air pollution has been documented as an important risk factor for chronic obstructive pulmonary disease (COPD), and inflammation is central to the development and progression of COPD. Single nucleotide polymorphisms (SNP) in some cytokine genes have been reported to be associated with COPD. We examined the association between 18 SNPs in 10 cytokine genes and COPD risk in a case-control study conducted in a population with high exposure to indoor smoky coal emissions. The study included 53 COPD cases and 122 healthy community controls. Carriers of the CSF2 117Ile allele had a 2.4-fold higher risk of COPD than the wild type (Thr/Thr) carriers (OR: 2.44; 95% CI: 1.10-5.41), and the AA genotype at IL8 -351 was associated with an increased risk of COPD (OR: 2.71; 95% CI: 1.04-7.04). When the combined effects of CSF2 117Ile and IL8 -351A were examined, individuals carrying at least one variant in both genes had a five-fold increased risk of COPD (OR: 5.14, 95% CI: 1.32-29.86). This study suggests that polymorphisms in both CSF2 and IL8 may play a role in the pathogenesis of COPD, at least in highly exposed populations. However, in view of our relatively small sample size, this study should be replicated in other populations with substantial exposure to indoor air pollutants such as polycyclic aromatic hydrocarbons (PAH) and particulate matter.

Polymorphisms in immunoregulatory genes, smoky coal exposure and lung cancer risk in Xuan Wei, China

We conducted a population-based case-control study in Xuan Wei, China, where lung cancer rates are among the highest in China due to exposure to indoor coal combustion products, to evaluate the association between polymorphisms in immunoregulatory genes and lung cancer risk. A total of 122 incident primary lung cancer cases and 122 individually matched controls were enrolled in Xuan Wei, China. Fifty single-nucleotide polymorphisms (SNPs) in 23 immunoregulatory genes involved in inflammation were genotyped and analyzed by logistic regression to assess the risk of lung cancer. A global test of association for 42 SNPs, which excluded eight SNPs that were in very tight linkage disequilibrium with other SNPs, was statistically significant (P = 0.01), suggesting that overall genetic variation in this pathway contributes to lung cancer risk. In addition, the IL1B -1060TT (i.e. -511TT) genotype was associated with increased lung cancer risk compared with the CC genotype [odds ratio (OR) = 2.27, 95% confidence interval (CI) = 1.05-4.91]. The IL8RA Ex2+860 GC or CC (OR = 0.27, 95% CI = 0.11-0.67), ICAM1 Ex2+100 AT or TT (OR = 0.39, 95% CI = 0.18-0.88) and IL12A Ex7+277 GA or AA (OR = 0.43, 95% CI = 0.22-0.84) genotypes were associated with decreased lung cancer risk. The protective effect of the IL8RA variant was stronger among subjects with high cumulative smoky coal use (> or = 130 tons) (OR = 0.11, 95% CI = 0.03-0.44; P(interaction) = 0.03). In conclusion, genetic variation in immunoregulatory genes may play an important role in the development of lung cancer in this population.

Smoky coal exposure, NBS1 polymorphisms, p53 protein accumulation, and lung cancer risk in Xuan Wei, China

Lung cancer rates in Xuan Wei County are among the highest in China and have been associated with exposure to indoor smoky coal emissions that contain high levels of polycyclic aromatic hydrocarbons (PAHs). The NBS1 gene product participates in DNA double-strand break repair and DNA damage-induced checkpoint activation, which are critical for maintaining genomic integrity. The p53 tumor suppressor gene is known to play key roles both in the maintenance of genomic stability in mammalian cells and in DNA damage surveillance. We examined the association between two common NBS1 polymorphisms (Leu34Leu, Gln185Glu) and lung cancer risk in a population-based case-control study in Xuan Wei, China. Individuals homozygous for the NBS1 34Leu or NBS1 185Glu variants were found to have an increased risk of lung cancer (odds ratio [OR] 2.15, 95% confidence interval [CI]: 0.91-5.10 and OR 2.53, 95% CI: 1.05-6.08, respectively). A haplotype containing the variant alleles from both NBS1 SNPs was associated with increased risk of lung cancer compared with the most common haplotype. Further, the associations were particularly pronounced among cases with over expression of p53 protein. These results suggest that NBS1 could be important in the pathogenesis of lung cancer in this population. However, additional studies in other populations with substantial environmental exposures to PAHs are needed to confirm our findings.

Polymorphisms in folate metabolic genes and lung cancer risk in Xuan Wei, China

The aim of this study is to investigate the role of genetic polymorphisms in twelve folate metabolism genes on the risk of lung cancer in Xuan Wei, China, where the lung cancer mortality rate is among the highest and is mainly caused by indoor smoky coal emissions. A total of 122 incident primary lung cancer cases and 122 matched controls were enrolled. Three single nucleotide polymorphisms were associated with increased risk of lung cancer including homozygotes of the C allele of CBS Ala360Ala (OR: 4.02; 95% CI: 1.64-9.87), the 222Val allele of MTHFR (OR: 2.32; 95% CI: 1.34-4.03), and the C allele of SLC19A1 Pro232Pro (OR: 1.83; 95% CI: 1.02-3.28). The distribution of CBS and MTHFR haplotypes differed between cases and controls (P=0.002 and P=0.07, respectively). In summary, three genetic variants in folate metabolism genes are associated with an increased risk of lung cancer in Xuan Wei, China.

Green tea consumption, genetic susceptibility, PAH-rich smoky coal, and the risk of lung cancer

Experimental evidence suggests that green tea ( Camellia sinesis) may reduce the risk of lung cancer through several hypothesized mechanisms including scavenging oxidative radicals, inhibition of tumor initiation, and modulation of detoxification enzymes. However, epidemiologic results have not been consistent as to the relationship between green tea consumption and lung caner prevention. We employed a population-based case-control study of 122 cases and 122 controls to investigate the effect that green tea consumption may have on the risk of lung cancer and whether polymorphisms in 8-oxoguanine-DNA glycosylase ( OGG1), glutathione- S-transferase M1 ( GSTM1), and aldo-keto reductase 1C3 ( AKR1C3) modify such an association. Daily green tea consumption was associated with a non-significant reduction in lung cancer risk. However, the effect of smoky coal exposure was higher for non-drinkers (odds ratio (OR) = 4.93; 95% confidence interval (95% CI) = 1.27–19.13) than for drinkers (OR = 1.88; 95% CI = 1.01–3.48). Further, among individuals with the OGG1 Cys 326 allele, daily consumption was associated with a 72% reduction (95% CI = 0.09–0.94). Among GSTM1 null homozygotes, those who consumed green tea daily had a non-significant reduction in risk compared with non-consumers. Green tea consumption had no effect among OGG1 Ser 326 homozygotes or GSTM1 carriers. In addition, AKR1C3 genotype did not modulate the effect of green tea consumption. The chemopreventive effects of green tea in this population may be restricted to individuals who are particularly susceptible to oxidative stress and oxidative DNA damage.

Polymorphisms in the DNA nucleotide excision repair genes and lung cancer risk in Xuan Wei, China

The lung cancer mortality rate in Xuan Wei County is among the highest in China and has been attributed to exposure to indoor smoky coal emissions that contain very high levels of polycyclic aromatic hydrocarbons (PAHs). Nucleotide excision repair (NER) plays a key role in reversing DNA damage from exposure to environmental carcinogens, such as PAHs, that form bulky DNA adducts. We studied single nucleotide polymorphisms (SNPs) and their corresponding haplotypes in 6 genes (ERCC1, ERCC2/XPD, ERCC4/XPF, ERCC5/XPG, RAD23B and XPC) involved in NER in a population-based case-control study of lung cancer in Xuan Wei. A total of 122 incident primary lung cancer cases and 122 individually matched controls were enrolled. Three linked SNPs in ERCC2 were associated with lung cancer with similar ORs; e.g., persons with the Gln allele at codon 751 had a 60% reduction of lung cancer (OR = 0.40, 95% CI 0.18-0.89). Moreover, one haplotype in ERCC2 was associated with a decreased risk of lung cancer (OR = 0.40, 95% CI 0.19-0.85) compared to the most common haplotype. In addition, subjects with one or 2 copies of the Val allele at codon 249 of RAD23B had a 2-fold increased risk of lung cancer (OR = 1.91, 95% CI 1.12-3.24). In summary, our results suggest that genetic variants in genes involved in the NER pathway may play a role in lung cancer susceptibility in Xuan Wei. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuan Wei and in other populations with substantial environmental exposure to PAHs.

Detection of p53 and K-ras mutations in sputum of individuals exposed to smoky coal emissions in Xuan Wei County, China

Lung cancer mortality rates in the Xuan Wei County population are among the highest in China and are associated with exposure to indoor emissions from the burning of smoky coal. Previous studies of lung tumors from both non-smoking women and smoking men in this region showed high frequencies of mutations, consisting mostly of G-->T transversions in the p53 tumor suppressor gene and K-ras oncogene, suggesting that these mutations were caused primarily by polycyclic aromatic hydrocarbons. In this study sputum samples from 92 individuals with no evidence of lung cancer from Xuan Wei County were screened for p53 and K-ras mutations. Sputum cells were collected on glass slides by sputum cytocentrifugation, stained and cytopathologically analyzed. Cytologically non-malignant epithelial cells were taken from each sputum sample using a laser capture microdissection microscope and molecularly analyzed. Cells taken from the sputum of 15 (16.3%) individuals were mutation positive, including 13 (14.1%) individuals each with a p53 mutation, 1 (1.1%) individual with a K-ras mutation and 1 (1.1%) individual with a p53 and a K-ras mutation. p53 mutations were found in both the sputum of individuals with evidence of chronic bronchitis (3 of 46 or 6.5%) and those without evidence of this disease (11 of 46 or 23.9%). Therefore, mutations in the p53 gene and, to a lesser extent, the K-ras gene were frequent in non-malignant epithelial cells taken from the sputum of individuals without evidence of lung cancer who were exposed to smoky coal emissions in Xuan Wei County and were at a high risk for developing the disease.

Molecular epidemiological studies on the relationship between indoor coal burning and lung cancer in Xuan Wei, China.

The lung cancer mortality rate in Xuan Wei County, China is among the highest in the country and has been associated with exposure to indoor smoky coal emissions that contain high levels of polycyclic aromatic hydro carbons. In a case-control study, it was found that the individual susceptibility to lung cancer risk may be increased by GSTM1 null genotype as well as overexpression of the p53 protein. It is likely that the lung cancer excess in Xuan Wei County results from the complex interaction of genetic and environmental factors that will require further research to be understood.

Mutation spectra of smoky coal combustion emissions in Salmonella reflect the TP53 and KRAS mutations in lung tumors from smoky coal-exposed individuals

Nonsmoking women in Xuan Wei County, Yunnan Province, China who use smoky coal for cooking and heating in poorly ventilated homes have the highest lung cancer mortality rate in China, and their lung cancer is linked epidemiologically to their use of smoky coal. The emissions contain 81% organic matter, of which 43% is polycyclic aromatic hydrocarbons (PAHs). Exposure assessment and molecular analysis of the lung tumors from nonsmoking women who use smoky coal strongly indicate that PAHs in the emissions are a primary cause of the elevated lung cancer in this population. Here we have determined the mutation spectra of an extract of smoky coal emissions in Salmonella TA98 and TA100; the extract was not mutagenic in TA104. The extract was 8.7× more mutagenic in TA100 with S9 than without (8.7 rev/μg versus 1.0 rev/μg) and was >3× more mutagenic in TA100 than in TA98—consistent with a prominent role for PAHs in the mutagenicity of the extract because PAHs are generally more mutagenic in the base-substitution strain TA100 than in the frameshift strain TA98. The extract induced only a hotspot mutation in TA98; another combustion emission, cigarette smoke condensate (CSC), also induces this single class of mutation. In TA100, the mutation spectra of the extract were not significantly different in the presence or absence of S9 and were primarily (78–86%) GC→TA transversions. This mutation is induced to a similar extent by CSC (78%) and the PAH benzo[ a]pyrene (B[ a]P) (77%). The frequency of GC→TA transversions induced in Salmonella by the extract (78–86%) is similar to the frequency of this mutation in the TP53 (76%) and KRAS (86%) genes of lung tumors from nonsmoking women exposed to smoky coal emissions. The mutation spectra of the extract reflect the presence of PAHs in the mixture and support a role for PAHs in the induction of the mutations and tumors due to exposure to smoky coal emissions.