Lung Cancer In Non-smoking Women Research Articles

Association of polycyclic aromatic hydrocarbons exposure scores and alteration of mitochondrial DNA copy number with female lung cancer risk among never smokers

To investigate the association of exposure to polycyclic aromatic hydrocarbons exposure scores and alteration of relative mitochondrial DNA copy number of blood with female lung cancer risk among never smokers. From August 2017 to August 2021, we enrolled all physician diagnosed new cases(n=465) of non-smoking female lung cancer from 12 tertiary and above hospitals in Liaoning, Jiangsu, Anhui and Qinghai provinces. And we selected matched non-smoking controls(n=463) by age and sex who were non-cancer and noncommunicable disease patients from the same hospital visited by the cases. Blood mitochondrial DNA copy number was detected by quantitative real-time polymerase chain reaction and estimated by relative quantification. We performed random forest and logistic regression to analyze the association of polycyclic aromatic hydrocarbons exposure scores and relative mitochondrial DNA copy number with the risk of female lung cancer among never smokers. We further analyzed the mediating effect and interaction models of polycyclic aromatic hydrocarbons exposure scores and mitochondrial DNA copy number levels on lung cancer in non-smoking women. The M(P25, P75) of polycyclic aromatic hydrocarbons exposure scores for cases and controls were 0.05(0.13, 0.16) and 0.08(0.24, 0.13), polycyclic aromatic hydrocarbons exposure scores of the cases was significantly higher than the controls(U=92130, P<0.05). The M(P25, P75) of mitochondrial DNA copy number for cases and controls were 0.90(0.71, 1.14) and 1.00(0.79, 1.21), mitochondrial DNA copy number of the cases was significantly lower than the controls(U=122559, P<0.05). Random forest and multivariable logistic regression analysis showed that the risk of lung cancer in non-smoking women increased with the increase of polycyclic aromatic hydrocarbons exposure scores(P_(trend)<0.05) and the decrease of relative mitochondrial DNA copy number(P_(trend)<0.05). The additive interaction between polycyclic aromatic hydrocarbons exposure scores and mitochondrial DNA copy number in non-smoking female lung cancer was statistically significant [API = 0.43(95%CI 0.19-0.67), SI = 2.84(95%CI 1.25-6.48). Mediation analysis showed mitochondrial DNA copy number had no significant mediating effect on the association between polycyclic aromatic hydrocarbons exposure scores and lung cancer in non-smoking women(Za×Zb: 95%CI-0.044-0.055). Minimize unnecessary polycyclic aromatic hydrocarbons exposures might significantly reduce the lung cancer risk among non-smoking women. Alteration of mitochondrial DNA copy number might become a potential biomarker in risk prediction of lung cancer of non-smoking women.

Bisphenol A and Di(2-Ethylhexyl) Phthalate promote pulmonary carcinoma in female rats via estrogen receptor beta: In vivo and in silico analysis

The prevalence of lung cancer in women currently merits our attentions. However, cigarette exposure alone does not tell the whole story that lung cancer is more prevalent among non-smoking women. Since female lung cancer is closely linked to estrogen levels, many of endocrine disrupting chemicals (EDCs), as the substances similar to estrogen, affect hormone levels and become a potential risk of female lung cancer. Additionally, the combined toxicity of EDCs in daily environment has only been discussed on a limited scale. Consequently, this study explored the cancer-promoting effect of two representative substances of EDCs namely Bisphenol A (BPA) and Di(2-Ethylhexyl) Phthalate (DEHP) after their exposure alone or in combination, using a rat pulmonary tumor model published previously, combining bioinformatics analysis based on The Comparative Toxicogenomics Database (CTD) and The Cancer Genome Atlas (TCGA) databases. It demonstrated that BPA and DEHP enhanced the promotion of pulmonary tumor in female rats, either alone or in combination. Mechanistically, BPA and DEHP mainly directly bound and activated ESR2 protein, phosphorylated CREB protein, activated HDAC6 transcriptionally, induced the production of the proto-oncogene c-MYC, and accelerated the formation of pulmonary tumor in female rats. Remarkably, BPA, rather than DEHP, exhibited a much more critical effect in female lung cancer. Additionally, the transcription factor ESR2 was most affected in carcinogenesis, causing genetic disruption. Furthermore, the TCGA database revealed that ESR2 could enhance the promotion and progression of non-small cell lung cancer in females via activating the WNT/β-catenin pathway. Finally, our findings demonstrated that BPA and DEHP could enhance the promotion of pulmonary carcinoma via ESR2 in female rats and provide a potential and valuable insight into the causes and prevention of lung cancer in non-smoking women due to EDCs exposure.

Extracellular domain of semaphorin 5A serves a tumor‑suppressing role by activating interferon signaling pathways in lung adenocarcinoma cells.

Semaphorin 5A (SEMA5A), which was originally identified as an axon guidance molecule in the nervous system, has been subsequently identified as a prognostic biomarker for lung cancer in nonsmoking women. SEMA5A acts as a tumor suppressor by inhibiting the proliferation and migration of lung cancer cells. However, the regulatory mechanism of SEMA5A is not clear. Therefore, the purpose of the present study was to explore the roles of different domains of SEMA5A in its tumor‑suppressive effects in lung adenocarcinoma cell lines. First, it was revealed that overexpression of full length SEMA5A or its extracellular domain significantly inhibited the proliferation and migration of both A549 and H1299 cells using MTT, colony formation and gap closure assays. Next, microarray analyses were performed to identify genes regulated by different domains of SEMA5A. Among the differentially expressed genes, the most significant function of these genes that were enriched was the 'Interferon Signaling' pathway according to Ingenuity Pathway Analysis. The activation of the 'Interferon Signaling' pathway was validated by reverse transcription‑quantitative PCR and western blotting. In summary, the present study demonstrated that the extracellular domain of SEMA5A could upregulate genes in interferon signaling pathways, resulting in suppressive effects in lung adenocarcinoma cells.

Identification of Significant Genes in Lung Cancer of Nonsmoking Women via Bioinformatics Analysis.

Background The aim of this study was to identify potential key genes, proteins, and associated interaction networks for the development of lung cancer in nonsmoking women through a bioinformatics approach. Methods We used the GSE19804 dataset, which includes 60 lung cancer and corresponding paracancerous tissue samples from nonsmoking women, to perform the work. The GSE19804 microarray was downloaded from the GEO database and differentially expressed genes were identified using the limma package analysis in R software, with the screening criteria of p value < 0.01 and ∣log2 fold change (FC) | >2. Results A total of 169 DEGs including 130 upregulated genes and 39 downregulated were selected. Gene Ontology and KEGG pathway analysis were performed using the DAVID website, and protein-protein interaction (PPI) networks were constructed and the hub gene module was screened through STING and Cytoscape. Conclusions We obtained five key genes such as GREM1, MMP11, SPP1, FOSB, and IL33 which were strongly associated with lung cancer in nonsmoking women, which improved understanding and could serve as new therapeutic targets, but their functionality needs further experimental verification.

Influencing factors of lung cancer in nonsmoking women: systematic review and meta-analysis.

Epidemiological studies have shown that some factors other than smoking may affect the risk of lung cancer in women, but the results are controversial. We conducted a meta-analysis to summarize the influencing factors of lung cancer in nonsmoking women. Both English and Chinese databases were searched for publications from 1990 to 2020. All included studies were assessed according to the Newcastle-Ottawa Scale (NOS). The pooled odds ratios (ORs) and 95% confidence interval (CI) of influential factors were analyzed using the meta-analysis method, and the publication bias and sensitivity were analyzed. Among the five categories, the pooled OR of cooking factors category was the highest. Among 42 influencing factors, there were frequent fried food (OR=2.42, 95% CI: 1.73-3.38) and long menstrual cycle (0.54, 95% CI: 0.39-0.75). A positive association of history of lung diseases/family lung/all cancer with lung cancer among Asian nonsmoking women (1.82, 95% CI: 1.60-2.07). Unlike other regions, cooking factors were the main risk factor for lung cancer in Asian. The meta-analysis suggests that cooking habits, diet, passive smoking, history of cancer and lung disease, and female reproduction are related to lung cancer in nonsmoking women. However, additional studies are warranted to extend this finding.

Mystery of rapid increase of lung cancer in non-smoking women

Mystery of rapid increase of lung cancer in non-smoking women

A qualitative study of healthcare-related experiences of non-smoking women with lung cancer.

Lung cancer in non-smoking women is a distinct entity, but few studies have examined these patients' healthcare-related experiences. Women with lung cancer and with no smoking history underwent a face-to-face semi-structured, audio-recorded interview that was analyzed with a qualitative inductive approach. Twenty-three patients were interviewed, and three themes emerged. The first theme centered on a delay in cancer diagnosis. One patient described, "The whole initial diagnostic process just fills me with rage… I didn't actually get my Tarceva® until the last week in April." Second, the diagnosis of lung cancer seemed especially challenging in view of patients' non-smoking history and otherwise good health; these factors seem to have contributed to the diagnostic delay. One patient explained, "Well, I was just so adamant that I didn't like smoking… maybe if I had been a smoker, they [the healthcare providers] would've been more resourceful." Finally, the stigma of a smoking-induced malignancy was clearly articulated, "Yeah. Because it's a stigma, and I had read that, too -- people go, 'Well, it's your own damn fault because you were a smoker.'" CONCLUSIONS: Non-smoking women with lung cancer appear to endure a long trajectory from symptoms to cancer diagnosis to the initiation of cancer therapy. An awareness and acknowledgement of this long trajectory might help healthcare providers render more compassionate cancer care to these patients.

Dysbiosis of the Salivary Microbiome Is Associated With Non-smoking Female Lung Cancer and Correlated With Immunocytochemistry Markers.

Background: Association between oral bacteria and increased risk of lung cancer have been reported in several previous studies, however, the potential association between salivary microbiome and lung cancer in non-smoking women have not been evaluated. There is also no report on the relationship between immunocytochemistry markers and salivary microbiota.Method: In this study, we assessed the salivary microbiome of 75 non-smoking female lung cancer patients and 172 matched healthy individuals using 16S rRNA gene amplicon sequencing. We also calculated the Spearman's rank correlation coefficient between salivary microbiota and three immunohistochemical markers (TTF-1, Napsin A and CK7).Result: We analyzed the salivary microbiota of 247 subjects and found that non-smoking female lung cancer patients exhibited oral microbial dysbiosis. There was significantly lower microbial diversity and richness in lung cancer patients when compared to the control group (Shannon index, P < 0.01; Ace index, P < 0.0001). Based on the analysis of similarities, the composition of the microbiota in lung cancer patients also differed from that of the control group (r = 0.454, P < 0.001, unweighted UniFrac; r = 0.113, P < 0.01, weighted UniFrac). The bacterial genera Sphingomonas (P < 0.05) and Blastomonas (P < 0.0001) were relatively higher in non-smoking female lung cancer patients, whereas Acinetobacter (P < 0.001) and Streptococcus (P < 0.01) were higher in controls. Based on Spearman's correlation analysis, a significantly positive correlation can be observed between CK7 and Enterobacteriaceae (r = 0.223, P < 0.05). At the same time, Napsin A was positively associated with genera Blastomonas (r = 0.251, P < 0.05). TTF-1 exhibited a significantly positive correlation with Enterobacteriaceae (r = 0.262, P < 0.05). Functional analysis from inferred metagenomes indicated that oral microbiome in non-smoking female lung cancer patients were related to cancer pathways, p53 signaling pathway, apoptosis and tuberculosis.Conclusions: The study identified distinct salivary microbiome profiles in non-smoking female lung cancer patients, revealed potential correlations between salivary microbiome and immunocytochemistry markers used in clinical diagnostics, and provided proof that salivary microbiota can be an informative source for discovering non-invasive lung cancer biomarkers.

Interaction Between Environmental Risk Factors and Catechol-O-Methyltransferase (COMT) and X-Ray Repair Cross-Complementing Protein 1 (XRCC1) Gene Polymorphisms in Risk of Lung Cancer Among Non-Smoking Chinese Women: A Case-Control Study.

BackgrpoundVarious studies have highlighted the link between polymorphisms in the XRCC1 gene (encoding X-ray repair cross-complementing group 1) with the incidence of decreased DNA repair capacity and an increased predisposition to cancer. Catechol-O-methyltransferase (COMT) plays a crucial role in estrogen-induced cancers. In the present study was analyzed the potential influence of XRCC1 and COMT gene polymorphisms as predisposing factors from a lung cancer perspective, in addition to conducting an investigation into their interaction with environmental risk factors in relation to lung cancer among non-smoking Chinese women.Material/MethodsThe XRCC1 gene T-77C, Arg194Trp, Arg280His, Arg399Gln, COMT gene 186C>T, and Val158Met mutations were evaluated in peripheral blood collected from 261 non-smoking female patients diagnosed with primary lung cancer and 265 female patients with benign lung disease.ResultThe results obtained from this study demonstrated that XRCC1–77TC + CC, XRCC1 399Gln/Gln, COMT 186CT + TT, COMT 158Val/Met genotypes, type of occupation, cooking-oil fumes, and soot exposures were all independent risk factors involved with the occurrence of lung cancer among non-smoking women. Moreover, interactions between environmental exposure factors as well as XRCC1 and COMT gene polymorphisms were determined to play significant contributory roles regarding susceptibility of non-smoking females to lung cancer.ConclusionsTaken together, T-77C and Arg399Gln polymorphisms of the XRCC1 gene, as well as the 186C>T and Val158Met polymorphisms of the COMT gene, increased the risk of lung cancer in non-smoking women, with the factors of occupation type, cooking-oil fumes, and soot exposures representing key contributing factors.

Meta-Analysis and Systematic Review in Environmental Tobacco Smoke Risk of Female Lung Cancer by Research Type.

More than 50% of women worldwide are exposed to Environmental Tobacco Smoke (ETS). The impact of ETS on lung cancer remains unclear. Cohort studies since the late 1990s have provided new evidence of female lung cancer risk due to ETS. The objective of this meta-analysis and systematic review was to analyze the association of ETS with female lung cancer risk from 1997 to 2017, organised based on research design. According to our applied inclusion and exclusion criteria, 41 published studies were included. The relative risk (RR) from the cohort studies or odds ratio (OR) from case-control studies were extracted to calculate the pooled risks based on the type of study. The summary risks of ETS were further explored with the modulators of ETS exposure sources and doses. The pooled risks of lung cancer in non-smoking women exposed to ETS were 1.35 (95% CI: 1.17–1.56), 1.17 (95% CI: 0.94–1.44), and 1.33 (95% CI: 1.17–1.51) for case-control studies, cohort studies, and both types of studies, respectively. The summary RR estimate of the cohort studies was not statistically significant, but the RR increased with increasing doses of ETS exposure (p trend < 0.05). Based on the results of this study, ETS might be an important risk factor of female lung cancer in non-smokers.

No association between global DNA methylation in peripheral blood and lung cancer risk in nonsmoking women: results from a multicenter study in Eastern and Central Europe.

Alterations in global DNA methylation have been suggested to play an important role in cancer development. We evaluated the association of global DNA methylation in peripheral blood with the risk of lung cancer in nonsmoking women from six countries in Central and Eastern Europe. This multicenter case-control study included primary, incident lung cancer cases diagnosed from 1998 to 2001 and controls frequency-matched for geographic area, sex, and age. Global methylation was assessed in peripheral blood DNA from 83 nonsmoking female cases and 181 nonsmoking female controls using the luminometric methylation assay (LUMA). Unconditional logistic regression models were used to estimate associations between DNA methylation in the blood and the risk of lung cancer. LUMA methylation level was not associated with the risk of lung cancer in nonsmoking women. Associations were not significantly different according to different strata of age, BMI, alcohol drinking, or second-hand tobacco smoke exposure status. In our study of nonsmoking women, the LUMA methylation level in peripheral blood was not associated with the risk of lung cancer. Our findings do not support an association of global blood DNA methylation with the risk of lung cancer in nonsmoking women.

Abstract 5315: Dietary intake and risk of lung cancer in non-smoking women: a hospital-based case-control study in Xuanwei and Fuyuan, China

Abstract Xuanwei and Fuyuan are rural counties in China that have the highest lung cancer rates in the country among non-smoking women. This alarming public health burden has been attributed to the combustion of smoky (bituminous) coal for heating and cooking, which can produce carcinogenic emissions such as polycyclic aromatic hydrocarbons (PAHs). Previous studies found that green leafy vegetables could absorb PAHs through air and direct soil contamination. Further, oral ingestion of PAHs was found be to associated with pulmonary adenoma development in animal feeding studies. Therefore, we investigated the associations between lung cancer risk and dietary intake of specific green leafy vegetables and other foods in non-smoking women of this farming region. We conducted a hospital-based case-control study of 1,074 female lung cancer patients and 977 frequency-matched controls from Xuanwei and Fuyuan, China in 2006-2013. Dietary intake was self-reported on questionnaires and categorized as never, several times/year, several times/month, several times/week, and every day. Unconditional logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI) of lung cancer in relation to intake of specific green leafy vegetables (i.e. lettuce, cabbage, fennel, spinach, hollow vegetables), corn, buckwheat, carrots, tomatoes, dried and fresh chili, pickled vegetables, bean curd, mushrooms, and preserved meats. Models were adjusted for age, county, first-degree relative with lung cancer, passive smoke exposure, education, lifetime smoky coal tonnage, respiratory disease history, time spent indoors, and menopausal status. Separate models were fitted for each dietary factor. We found that increased consumption of several green leafy vegetables was associated with increased risk of lung cancer. Eating hollow vegetables every day was associated with 2.50 (95% CI: 1.18, 5.27) times the odds of lung cancer compared to never. Similarly, eating lettuce (OR=2.13, 95% CI: 1.41, 3.21) and cabbage (OR=1.82, 95% CI: 1.21, 2.69) every day was associated with increased risks compared to several times a year or less. Conversely, eating bean curd (OR=0.54, 95% CI: 0.40, 0.72) several times a week was associated with decreased risk compared to several times a year or less; while eating buckwheat (OR=0.59, 95% CI: 0.40, 0.89) several times a week was associated with decreased risk compared to never. No significant associations were found for fennel, spinach, and other foods. Our findings suggest that increased consumption of a variety of green leafy vegetables may be related to elevated lung cancer risk in non-smoking women from Xuanwei and Fuyuan, China, independent of other risk factors. The increased risk may be due to environmental contamination of crops from coal combustion. Conversely, frequent consumption of bean curd and buckwheat was found to be protective. Citation Format: Jason Y. Wong, Bryan A. Bassig, Wei Hu, Jinming Zhang, Wei Jie Seow, Neil E. Caporaso, Bu-tian Ji, Robert S. Chapman, George S. Downward, Jihua Li, Jun He, Kaiyun Yang, Yunchao Huang, Roel Vermeulen, Nathaniel Rothman, Qing Lan. Dietary intake and risk of lung cancer in non-smoking women: a hospital-based case-control study in Xuanwei and Fuyuan, China [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5315. doi:10.1158/1538-7445.AM2017-5315

Women and Lung Cancer: What is New?

In the last 20 years, there has been an increased focus on gender differences in health and disease. The earliest studies of lung cancer enrolled mainly men, as the incidence of lung cancer among women was exceedingly low. As social patterns changed around World War II and women began to smoke more, the epidemiology of lung cancer has changed. The higher percentage of lung cancer in nonsmoking women as compared with nonsmoking men suggests that lung cancer behaves differently in women. Studies of lung cancer in women indicate that there are differences in risk factors, histology, pathophysiology, treatment outcomes, and prognosis as compared with men. The purpose of this review is to provide a concise summary of the literature on lung cancer as it pertains to women, with an emphasis on new areas of research and treatment options.

Attributable causes of lung cancer incidence and mortality in China.

The aims of our study were to estimate the contribution of known lung cancer risk factors, and provide evidence to support the National Cancer Prevention and Control Program in China. We calculated the proportion of lung cancer attributable to specific risk factors. Data on exposure prevalence were from meta-analyses and large-scale national surveys of representative samples of the Chinese population. Data on relative risks were from meta-analyses and large-scale prospective studies. Lung cancer mortality and incidence were taken from the Third National Death Survey and from cancer registries in China. We estimated that in China 285 304 lung cancer deaths and 327 465 cases were attributable to smoking, involuntary smoking (women only), occupational exposure, indoor radon, and low fruit intake in 2005. The proportion of lung cancer deaths attributable to smoking, involuntary smoking among non-smoking women, occupational exposure, indoor radon and low fruit intake was 56.9%, 11.1%, 9.5%, 0.2% and 12.4%, respectively. About 41% of lung cancer mortality and incidence in women was caused by risk factors in our study. However, over half of lung cancer deaths and cases among women were not attributable to known risk factors. It is necessary to conduct large-scale studies to identify additional risk factors of lung cancer in non-smoking women.

Body mass index and risk of lung cancer in no-smoking women: A prospective cohort study in urban Shanghai

Objective:To investigate the association between BMI(Body Mass Index) and risk of lung cancer in non-smoking women in urban Shanghai.Methods:A total of 74 942 female residents aged 40 to 70 years in urban Shanghai were recruited in a prospective cohort from 1997 to 2000.They were actively followed up every two years.Until December in 2007,271 incident cases of lung cancer in no-smoking women were identified in the cohort.COX regression model was used to estimate the adjusted relative risks(RR) and 95% confidence intervals(95% CI).Results:After adjustment for age,education level,menopause status and other potential confounding factors,there were no association of baseline BMI and 20-year BMI with risk of lung cancer.The highest quartiles of baseline BMI group experienced 0.95 fold risk(95%CI:0.67-1.34) of lung cancer compared with their counterpart with lowest quartile.Compared with those with lowest quartile of BMI when aged 20 years,women who with the highest quartiles experienced 0.77 fold decreased risk(95%CI:0.52-1.15).Similar results were obtained after stratified analysis on the association of baseline BMI with risk of lung cancer in non-smoking women.Conclusion:BMI was not associated with the risk of lung cancer in no-smoking women older than 40 years in urban Shanghai.

Carcinogenicity of household solid fuel combustion and of high-temperature frying

In October, 2006, 19 scientists from eight countries met at the International Agency for Research on Cancer (IARC) in Lyon, France, to assess the carcinogenicity of household solid fuel combustion (coal and biomass) and of high-temperature frying. These assessments will be published as volume 95 of the IARC Monographs. About half of the world’s population, mostly in low-resource and mediumresource coun tries, use solid fuels for cooking or heating, often in poorly ventilated spaces. WHO identifi ed in door smoke from combustion of solid fuels as one of the top ten risks for worldwide burden of disease. Products of incomplete combustion contain respirable (coarse, fi ne, and ultrafi ne) particles and many volatile and nonvolatile organic compounds, including carcinogens such as benzo[a]pyrene, formaldehyde, and benzene. Average indoor concen trations of particulate matter (<10 μm) can be as high as several milligrams per cubic metre, with peak concentrations an order of magnitude higher. Women and young children who are at home for most of the day are most highly exposed. Although occupational exposure to the combustion products of coal by inhalation is known to cause lung cancer, many studies, mostly from China, now show similar eff ects from household use of coal. The problem was fi rst noted in the county of Xuan Wei, China, where the type of coal used produces especially smoky emissions. Two case–control studies from Xuan Wei reported a positive exposure– response relationship between the amount of coal used and the risk of lung cancer. Subsequently, a cohort intervention study showed transition to the use of a stove with a chimney from one without reduced this risk. A large study in Shenyang, China, noted positive exposure–response associations for diff erent measures of exposure to coal smoke—including a cumulative index of indoor exposure— after adjust ing for smoking and education. Furthermore, a study of non-smoking women in Harbin, China, reported a strong exposure–response relationship between years of use of a coal stove and lung cancer. Case– control studies from Taiwan and the USA have also reported a twofoldincreased risk for lung cancer as a result of coal-smoke inhalation after adjusting for potential confounders. In experiments with animals, inhalation of emissions from coal, burned under conditions similar to those in Xuan Wei, increased the incidence of various types of malignant lung tumours in male and female Kunming mice and of squamous-cell carcinomas in male and female Wistar rats. In another study, the incidence of adenocarcinoma of the lung was increased in male and female Kunming mice exposed to combustion emissions of coal obtained from Harbin. On the basis of suffi cient evidence in both humans and experimental animals, the Working Group concluded that indoor emissions from household combustion of coal are “carcinogenic to humans (Group 1)”. Mechanistic data from studies of humans and animals are consistent with this conclusion. Biomass fuel is much more widely used than coal but the adverse health eff ects have been studied less. In Taiwan, women who burned wood for cooking had a threefold increase in the risk of lung cancer after adjusting for potential confounders. Additionally, a large multicentre European case– control study recorded an adjusted 20–30% increased risk of lung cancer in people who burned wood but not coal, compared with people who never used coal or wood for cooking or heating. Studies in Japan and Mexico also found an increased risk of lung cancer in non-smoking women, which was related to their exposure to smoke from wood or straw. These studies suggest that exposure to smoke from wood combustion is associated with an increased risk of lung cancer; however, the results on exposure duration and intensity are diffi cult to interpret. In animal experiments, exposure to emissions from wood, burned under conditions similar to those in Xuan Wei, increased the incidence of lung adenocarcinomas in male and female Kunming mice, but not in Wistar rats. Extracts from wood smoke, applied to the skin or given subcutaneously, produced cancer in mice and rats. Combustion emissions from wood are mutagenic because of the presence of compounds from various chemical classes, including polycyclic aromatic hydrocarbons and acidic or polar substances. Molecular data, which include changes in expression and phosphorylation of P53 in patients with lung cancer who were exposed to wood smoke, and systemic genotoxicity in charcoal workers and in women who burn cow dung or wood, supports evidence of carcinogenicity of emissions from burning wood. On the basis of limited evidence of carcinogenicity of biomass combustion emissions (mainly from wood) in humans and experimental animals; suffi cient evidence of carcino genicity of wood-smoke extracts in experimental animals; and strong evidence of mutagenicity, Upcoming meetings

Study on risk factors of lung cancer in non-smoking women

Lung cancer is a serious health problem in public. Its morbidity and mortality have been increasing rapidly. The mortality of lung cancer in women also increases year by year, in which most of the cases are non-smoking women, and the risk factors still are unclear. The aim of this study is to explore the effects of air pollution in room, passive smoking and other factors on risk of lung cancer. A total of 618 newly diagnosed female patients with primary lung cancer were enrolled. The controls were selected randomly in the general population in urban districts. Two trained interviewers performed this interview face-to-face using the same questionnaire. The content of questionnaire included the characteristics of demography, history of passive smoking, exposed history of cooking fume, fuel exposure, exposed history of coal fume, history of using 'Kang', pulmonary disease history, cancer history of relatives and occupational history. Passive smoking in childhood was related with lung cancer of non-smoking women (OR= 1.81 , 95%CI=1.46-2.24). The exposure to the cooking fume was of great significance (OR=3.18, 95%CI= 2.55 -3.97). The relationship between coal fume and lung cancer was significant (OR=2.56, 95%CI= 1.83 -4.55). The pulmonary disease history including tuberculosis, chronic bronchitis, asthma, pneumonia, emphysema was strongly associated with lung cancer (OR=1.80, 95%CI=1.43-2.27). The family history of cancer significantly increased the risk of lung cancer (OR=2.09, 95%CI=1.46-3.00), especially the lung cancer history in the first relatives (OR=2.46, 95%CI=1.55-3.90). After adjusting other factors, logistic analysis showed that cooking fume (OR=4.11, 95%CI=2.14-7.89), the pulmonary disease history (OR= 2.05 , 95%CI=1.08-3.93), and the family history of lung cancer (OR=2.89, 95%CI=1.30-6.41) were significant factors. The results show that passive smoking in childhood, cooking oil exposure, coal fume exposure, pulmonary disease history including tuberculosis and family history of lung cancer are risk factors of lung cancer in non-smoking women.

Risk factors for lung cancer among nonsmoking women.

To evaluate risk factors for lung cancer in nonsmoking women, we used data of a case-control study conducted between 1991 and 1996 in Germany. A total of 234 female histologically confirmed lung cancer patients and 535 population controls who had never smoked more than 400 cigarettes in their lifetime were personally interviewed with respect to occupation, exposure to environmental tobacco smoke (ETS), family history of cancer, prior physician-diagnosed lung diseases or cancer and diet. One-year radon measurements in the last dwelling were performed. Odds ratios (OR) adjusted for age and region and 95% confidence intervals (CI) were calculated via logistic regression. When cumulative duration of exposure to ETS in hours was considered, the OR for high compared to not or low ETS exposed women was 2.62 (CI:1.35-5.06) for occupational exposure and OR=1.67 (CI:0.86-3.25) for spousal exposure, exhibiting a significant trend for ETS at work. Working more than 10 years in jobs or industries with known or suspected lung carcinogens was associated with OR=2.0 (CI:0.99-4.0). An elevated risk due to prior lung diseases was present for pneumonia (OR=1.6; CI:1.07-2.40) and tuberculosis (OR=1.6; CI:0.77-3.37). No significant increase in risk with increasing residential radon levels or with the presence of a family history of lung cancer was apparent. Protective effects were observed for high vs. low consumption of fresh vegetables (OR=0.5; CI:0.25-0.82) and cheese (OR=0.3, CI:0.21-0.55). ETS at work, occupational hazards and previous pneumonia may be risk factors for lung cancer in nonsmoking women, while a diet rich in fresh vegetables and cheese seems to be protective.

Revisiting the Association between Environmental Tobacco Smoke Exposure and Lung Cancer Risk

Hackshaw et al. estimated that adjustment for bias due to misclassification of smoking habits reduces the observed relative risk of lung cancer in non-smoking women associated with smoking by the husband from 1.24 to 1.18. This bias estimate is little affected by using an alternative method for misclassification adjustment or by using updated data from 47 studies rather than data from the 37 studies used by Hackshaw et al. The bias is increased if strong evidence of much higher misclassification rates in Asian women is taken into account and could then explain about half the observed association. Misclassification correction has not previously been attempted for dose-response data. We describe a suggested approach and apply it to data relating risk to amount smoked by the husband. As shown in paper II of this series the unadjusted increase in risk per 10 cigarettes/ day smoked by the husband is 10% (95% CI 5 to 15%), reducing to either 6% (95% CI 1 to 11%) or 9% (95% CI 5 to 14%) after adjustment for confounding by fruit, vegetable and fat consumption and education using respectively unweighted or weighted means to combine evidence on the ETS/confounder association from different studies. Further adjustment for plausible levels of misclassification similarly reduced these two estimates to, respectively, 2% (95% CI –3 to 8%) or 5.5% (95% CI 0 to 11%). Difficulties in applying misclassification bias corrections are discussed. Other sources of bias will be considered in later papers in this series.

Metabolites of a tobacco-specific lung carcinogen in nonsmoking women exposed to environmental tobacco smoke.

Environmental tobacco smoke (ETS) is associated with lung cancer in nonsmokers. Most epidemiologic studies find a higher risk for lung cancer in nonsmoking women married to smokers than in those married to nonsmokers. We measured metabolites of a tobacco-specific lung carcinogen in urine from healthy, nonsmoking women exposed to ETS. We recruited women and their partners through advertisements. Couples completed questionnaires on smoking history and demographics, and both partners provided 100 mL of urine; 23 women had male partners who smoked in the home (i.e., exposed women), and 22 women had male partners who did not smoke (i.e., unexposed women). Urine samples were analyzed for nicotine, for cotinine, for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc), as well as for creatinine. NNAL and NNAL-Gluc are metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Unpaired Student's t tests were conducted on log-transformed values. All statistical tests are two-sided. Urinary levels of nicotine, cotinine, NNAL, and NNAL-Gluc were statistically significantly higher in exposed women than in unexposed women. Geometric means for these compounds in exposed versus unexposed women, respectively, were as follows: nicotine, 0.050 nmol/mg of creatinine (95% confidence interval [CI] = 0.033 to 0.076) versus 0.008 nmol/mg of creatinine (95% CI = 0.004 to 0.014); cotinine, 0.037 nmol/mg of creatinine (95% CI = 0.022 to 0.061) versus 0.007 nmol/mg of creatinine (95% CI = 0.004 to 0.011); NNAL, 0.013 pmol/mg of creatinine (95% CI = 0.007 to 0.024) versus 0.004 pmol/mg of creatinine (95% CI = 0.002 to 0.007); and NNAL-Gluc, 0.027 pmol/mg of creatinine (95% CI = 0.016 to 0.045) versus 0.004 pmol/mg of creatinine (95% CI = 0.003 to 0.006). Nonsmoking women exposed to ETS take up and metabolize the tobacco-specific lung carcinogen NNK, which could increase their risk of lung cancer. Within couples, the NNAL plus NNAL-Gluc level in exposed women compared with that of their smoking partners averaged 5.6%. Notably, epidemiologic studies have estimated the excess risk for lung cancer in nonsmoking women exposed to ETS as 1%-2% of that in smokers.