吸烟与氡暴露致肺癌的流行病学和生物学差异

吸烟和氡暴露是导致肺癌的两个主要危险因素。本文从流行病学和生物学分子效应两个方面,总结了吸烟和氡暴露致肺癌的近期研究结果,比较了二者的人群和生物学差异,并提出了今后的研究建议。     

吸烟与氡导致肺癌的氧化损伤与基因突变异同

吸烟与氡是导致肺癌的两个主要因素，氧化损伤和基因突变是两个主要的机制。氧化损伤涉及多种自由基，而发生突变的基因主要包括p53基因、K-ras基因、p16基因、O^6-MGMT基因和FHIT基因。通过对吸烟和氡致肺癌的氧化损伤与基因突变方面的对比研究，可为肺癌发生的机制提供新的线索。     

肺癌患者支气管肺泡灌洗液中K-ras基因第1外显子点突变与吸烟的关系

[目的 ]探讨支气管肺泡灌洗液 (BALF)细胞中K ras原癌基因点突变与吸烟的关系及其在肺癌早期诊断中的意义。 [方法 ]应用聚合酶链反应结合限制性片段长度多态性分析法 (PCR RFLP) ,检测了 3 7例吸烟肺癌患者、2 5例非吸烟肺癌患者以及 2 0例肺良性疾病支气管肺泡灌洗液细胞中K ras基因第 12位密码子突变的情况。 [结果 ]肺癌患者K ras基因突变率为 3 5 5 % (2 2 / 62 ) ,肺良性疾病中未发现有K ras基因突变者。突变的发生与患者的年龄及吸烟史有关 ,与性别、TNM分期无关 ;另外 ,重度吸烟者突变率 (68 8% )高于轻度 (2 5 0 % )及中度吸烟者 (3 0 8% ) ,(P <0 0 5 ) ,更明显地高于非吸烟者 (2 0 0 % ) ,(P <0 0 1)。 [结论 ]①吸烟可能是导致K ras基因突变的重要因素之一 ;②BALF细胞中K ras基因突变的检测对肺癌有一定的早期诊断价值 ,可以协助纤维支气管镜提高对周围型肺癌的诊断率     

病因分值在病例对照研究中的应用──肺癌危险因素的交互效应

对广东省２００例原发性女性肺癌的现患病人作１：１配对病例对照研究，在Ｍａｎｔｅｌ－Ｈａｅｎｓｚｅｌ分层分析和条件ｌｏｇｉｓｔｉｃ回归分析的基础上，探讨女性肺癌危险因素的病因分值以及被动吸烟与其他各种危险因素间的交互效应。多因素条件ｌｏｇｉｓｔｉｃ回归分析结果显示：被动吸烟，厨房通风，喜吃咸食，慢性支气管炎、家庭肿瘤史，肺结核，。服和避孕药是女性肺癌独立的危险因素。     

病因分值在病例对照研究中的应用──肺癌危险因素的交互效应

对广东省200例原发性女性肺癌的现患病人作1：1配对病例对照研究，在Mantel-Haenszel分层分析和条件logistic回归分析的基础上，探讨女性肺癌危险因素的病因分值以及被动吸烟与其他各种危险因素间的交互效应。多因素条件logistic回归分析结果显示：被动吸烟（丈夫）、厨房通风、喜吃咸食、慢性支气管炎史、家族肿瘤史、肺结核、服用避孕药是女性肺癌独立的危险因素（OR=2.16～40．55，P＜0．05）。它们的病因分值分别是0.535.0．432、0.252、0．124、0.115、0．072.0．069。分析被动吸烟（丈夫）与口服避孕药、家族肿瘤史、厨房通风、肺结核史、经常吃咸色或腌菜间交互作用，其病因分值分别为0．848、0．499、0．479、0.416、0．346.交互作用指数是0．906、0．543、0．578、0．427、0．441。研究提示被动吸烟是女性肺癌的重要危险因素，特别是丈夫吸烟，尤其是在与服用避孕药这一因素并存的情况下，增加女性肺癌的危险性。     

Lung Cancer in a U.S. Population with Low to Moderate Arsenic Exposure

Background

Little is known about the carcinogenic potential of arsenic in areas with low to moderate concentrations of arsenic (< 100 μg/L) in drinking water.

Objectives

We examined associations between arsenic and lung cancer.

Methods

A population-based case–control study of primary incident lung cancer was conducted in 10 counties in two U.S. states, New Hampshire and Vermont. The study included 223 lung cancer cases and 238 controls, each of whom provided toenail clippings for arsenic exposure measurement by inductively coupled–plasma mass spectrometry. We estimated odds ratios (ORs) of the association between arsenic exposure and lung cancer using unconditional logistic regression with adjustment for potential confounders (age, sex, race/ethnicity, smoking pack-years, education, body mass index, fish servings per week, and toenail selenium level).

Results

Arsenic exposure was associated with small-cell and squamous-cell carcinoma of the lung [OR = 2.75; 95% confidence interval (CI), 1.00–7.57] for toenail arsenic concentration ≥ 0.114 μg/g, versus < 0.05 μg/g. A history of lung disease (bronchitis, chronic obstructive pulmonary disease, or fibrosis) was positively associated with lung cancer (OR = 2.86; 95% CI, 1.39–5.91). We also observed an elevated risk of lung cancer among participants with a history of lung disease and toenail arsenic ≥ 0.05 μg/g (OR = 4.78; 95% CI, 1.87–12.2) than among individuals with low toenail arsenic and no history of lung disease.

Conclusion

Although this study supports the possibility of an increased risk of specific lung cancer histologic types at lower levels of arsenic exposure, we recommend large-scale population-based studies.     

Exposure to and annoyance with second-hand smoke in Switzerland: results of the Tobacco Monitoring survey

Summary. Objectives: To present selected results on exposure to secondhand smoke and experienced annoyance with second-hand smoke in the Swiss population, particularly in restaurants and in the workplace. Methods: The data were collected as part of the Swiss Survey of Tobacco Use (“Tobacco Monitoring”) commissioned by the Swiss Federal Office of Public Health. It is a representative, continuous survey of tobacco consumption among 14- to 65-year-olds in Switzerland. Since January 2001, four times a year a new sample of 2 500 persons has been taken (i. e. 10 000 participants annually). The survey was conducted using standardized telephone interviews in German, French and Italian. Results: Approximately half of the working population in Switzerland is exposed to second-hand smoke in the workplace. In restaurants, cafes and bars, nearly 9 out of 10 people are exposed to environmental tobacco smoke. Non-smokers in particular report annoyance with second-hand smoke. Conclusions: The Swiss population has a high level of exposure to second-hand smoke. There is a need for public health educational programs and legislation aiming at banning smoking in public areas and in the workplace.

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Zusammenfassung. Passivrauch-Exposition und subjektiv empfundene Bel?stigung durch Tabakrauch in der Schweiz: Resultate der Schweizerischen Umfrage zum Tabakkonsum (Tabakmonitoring) Fragestellung: Im vorliegenden Artikel finden sich ausgew?hlte Ergebnisse zur Passivrauchexposition der Schweizer Bev?lkerung sowie zur dadurch hervorgerufenen, subjektiv empfundenen Bel?stigung. Insbesondere wird auf das Passivrauchen in Gastst?tten und am Arbeitsplatz eingegangen. Methoden: Die Daten wurden im Rahmen der Schweizerischen Umfrage zum Tabakkonsum (Tabakmonitoring) erhoben. Mit dem Tabakmonitoring wird der Tabakkonsum der 14- bis 65-j?hrigen Wohnbev?lkerung der Schweiz repr?sentativ und kontinuierlich erfasst. Seit Januar 2001 wird in jedem Quartal ein neues Sample mit 2 500 Personen gezogen, so dass pro Jahr die Antworten von insgesamt 10 000 Befragten zur Verfügung stehen. Die Befragung erfolgt mittels vollstandardisierter Telefoninterviews in deutscher, franz?sischer und italienischer Sprache. Ergebnisse: Rund die H?lfte der Erwerbst?tigen in der Schweiz ist am Arbeitsort dem Passivrauch ausgesetzt. In Restaurants, Cafés und Bars sind es fast neun von 10 Personen, die dem Tabakrauch anderer ausgesetzt sind. Vor allem die tabakrauchexponierten Nichtraucherinnen und Nichtraucher fühlen sich dadurch stark bel?stigt. Schlussfolgerungen: Die Schweizer Bev?lkerung hat eine hohe Passivrauchexposition. Einerseits sollte das Wissen über die Sch?dlichkeit des Passivrauchens verst?rkt der ?ffentlichkeit vermittelt werden. Andererseits braucht es gesetzliche Massnahmen zum Schutz der Nichtraucher, insbesondere in Gastst?tten und am Arbeitsplatz.

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Résumé. Exposition à la fumée passive et impression subjective de gêne provoquée par le tabagisme passif en Suisse: Résultats de l’enquête suisse sur le tabagisme (“Monitorig Tabac”) Objectifs: Présenter une partie des résultats concernant l’exposition de la population suisse au tabagisme passif et l’incommodation ressentie, ce spécialement dans les lieux publics et sur le lieu de travail. Méthodes: Les données sur le tabagisme passif sont issues du “Monitorig Tabac”. Elles permettent de recenser de manière permanente et représentative la consommation de tabac chez les personnes agées de 14 à 65 ans domiciliées en Suisse. Depuis janvier 2001, un échantillon de 2 500 personnes est tiré trimestriellement (soit 10 000 personnes par an). Le sondage est effectué au moyen d’entretiens téléphoniques entièrement standardisés en fran?ais, allemand et italien. Résultats: Environ la moitié de la population active en Suisse est exposée au tabagisme passif. Dans les restaurants, les cafés et les bars, près de neuf personnes sur 10 subissent le tabagisme des fumeurs. Ce sont en particulier les personnes nonfumeuses qui se sentent fortement dérangées par le tabagisme passif. Conclusions: La population suisse est largement exposée au tabagisme passif. L’information concernant les effets du tabagisme passif devrait être renforcée. Des bases légales permettant une protection des non-fumeurs, en particulier dans les espaces publics et sur le lieu de travail, devraient être créées.

     

Use of an Asbestos Exposure Score and the Presence of Pleural and Parenchymal Abnormalities in a Lung Cancer Case Series

Abstract

To assess whether there was an association between asbestos exposure and abnormalities on chest x-rays or CT scans, chest radiographs and CT scans of 103 asbestos-exposed patients with known lung cancer were reviewed for pleural or parenchymal abnormalities. Asbestos exposure was assessed using an asbestos exposure index that integrated time and intensity of reported exposure via a weighting scheme. Chest CT scans were clearly more sensitive in detecting pleural or parenchymal abnormalities than were standard PA chest x-rays. Furthermore, there was a significant correlation between higher asbestos exposure index scores and abnormalities on CT scans. Multivariable logistic regression models were used to investigate the relationship between the asbestos exposure index score and pleural or parenchymal abnormalities after adjusting for gender, pack-years of smoking, and cell type. None of these variables was associated with abnormalities on chest x-rays or CT scans. An asbestos exposure score > 10 was associated with pleural or parenchymal abnormalities (OR = 4.93; 95% CI 1.05–23.12). The results suggest that assessment of asbestos exposures by means of an algorithm-based index can classify the exposures accurately for epidemiologic studies.     

A Genome‐Wide Association Study for Serum Bilirubin Levels and Gene‐Environment Interaction in a Chinese Population

Bilirubin is an effective antioxidant and is influenced by both genetic and environmental factors. Recent genome‐wide association studies (GWAS) have identified multiple loci affecting serum total bilirubin levels. However, most of the studies were conducted in European populations and little attention has been devoted either to genetic variants associated with direct and indirect bilirubin levels or to the gene‐environment interactions on bilirubin levels. In this study, a two‐stage GWAS was performed to identify genetic variants associated with all types of bilirubin levels in 10,282 Han Chinese individuals. Gene‐environment interactions were further examined. Briefly, two previously reported loci, UGT1A1 on 2q37 (rs6742078 and rs4148323, combined P = 1.44 × 10^?89 and P = 5.05 × 10^?69, respectively) and SLCO1B3 on 12p12 (rs2417940, combined P = 6.93 × 10^?19) were successfully replicated. The two loci explained 9.2% and 0.9% of the total variations of total bilirubin levels, respectively. Ethnic genetic differences were observed between Chinese and European populations. More importantly, a significant interaction was found between rs2417940 in SLCO1B3 gene and smoking on total bilirubin levels (P = 1.99 × 10^?3). Single nucleotide polymorphism (SNP) rs2417940 had stronger effects on total bilirubin levels in nonsmokers than in smokers, suggesting that the effects of SLCO1B3 genotype on bilirubin levels were partly dependent on smoking status. Consistent associations and interactions were observed for serum direct and indirect bilirubin levels.     

大丰市居民吸烟指数与胃癌患病关系的病例对照研究

[目的]探讨吸烟指数与胃癌的关系,以便为胃癌的防治提供依据。[方法]对2003年1月1日至2008年6月大丰市647例新发胃癌患者和2 340名健康对照进行单因素非条件Logistic回归分析。[结果]男性、女性和男女合计的吸烟率,均为胃癌病例组高于对照组(P0.01)。单因素非条件Logistic回归分析结果,吸烟指数达到200.00以上时与胃癌患病有关联(P0.01),随着吸烟指数的增大,胃癌患病的OR值随之增大。[结论]吸烟是胃癌发病的危险因素之一,且危险性随着吸烟指数的增加而增大。     

Smoking Exposure Is Associated with Serum Vitamin D Deficiency in Children: Evidence from the Japan Environment and Children’s Study

Tobacco smoke exposure is known to lower serum 25-hydroxyvitamin D (25(OH)D) concentrations. This study evaluated the association between passive smoking and vitamin D deficiency (VDD) in young children using data from the Japan Environment and Children’s Study (JECS), the largest birth cohort study in Japan. Information on parental smoking status was extracted from a survey of JECS for children aged 1.5 years and data for serum 25(OH)D concentrations were obtained from blood tests in the Sub-Cohort Study of JECS performed at age 2 years. Logistic regression and linear models were fitted to evaluate the association between these variables. Data were analyzed for 4593 children. After adjusting for covariates, smoke exposure was significantly associated with increased incidence of VDD (OR 1.35; 95% CI, 1.14–1.59) according to the logistic model. The linear model indicated that passive smoking negatively predicted de-seasonalized serum 25(OH)D concentrations (β −0.5; 95% CI −0.95 to −0.08) in children aged 2 years. The results suggest that smoke exposure is a risk factor for VDD in children. Given that VD plays a crucial role in bone metabolism and the immune system, our findings are significant for clinical and public health.     

Confirmatory Factor Analysis and Sample Invariance of the Chinese Patient Satisfaction Questionnaire (ChPSQ-9) among Patients with Breast and Lung Cancer

Objectives:  Previous exploratory factor analysis of the 9-item Chinese Patient Satisfaction Questionnaire (ChPSQ-9) identified two dominant factors: doctor and nurse. The present study employed confirmatory factor analysis (CFA) to examine the factorial invariance of the ChPSQ-9 between and within samples of Chinese patients with breast or lung cancer.
Methods:  Longitudinal data were analyzed from Chinese breast and lung cancer patients who had completed the ChPSQ-9 during their first outpatient visit, at 3 months, and at 6 months after baseline. CFAs tested the fit of a one-factor model, a hierarchical model that comprised a general latent factor and two first-order factors, and a correlated model that comprised two correlated first-order factors to the data. The factorial invariance of the ChPSQ-9 between six independent samples across time was investigated using multigroup CFAs.
Results:  The CFA's results demonstrated a better fit of the correlated model over the one-factor model and the hierarchical model in the breast and lung cancer samples. The correlated model showed evidence of cross-sample and longitudinal factorial invariance. Patients were generally satisfied with services provided by doctors and nurses. Internal consistency of the scale was also good for both cancer samples across time.
Conclusions:  The ChPSQ-9 is a valid and reliable instrument to be employed among breast and lung cancer patients, in clinical settings or intervention research, to evaluate group differences in patient satisfaction and its association with intervention effectiveness.     

Use of a Smartphone Self-assessment App for a Tobacco-Induced Disease (COPD,Cardiovascular Diseases,Cancer) Screening Strategy and to Encourage Smoking Cessation: Observational Study

BackgroundPatient self-assessment via a mobile app detects actionable symptoms and has been shown to detect lung cancer relapses early, thereby lengthening survival.ObjectiveThe purpose of this study was to assess the incidence of chief symptoms associated with the main tobacco-induced pathologies in both current and ex-smokers through a self-assessment smartphone app and to evaluate the app’s capacity to encourage users to quit smoking or reduce consumption, as well as its impact on early lung cancer stages at the time of diagnosis.MethodsCurrent and ex-smokers were recruited through an advertising campaign in Sarthe county (France) proposing the free download of a smartphone app. App users were asked to answer 13 questions related to symptoms associated with tobacco-induced diseases (chronic obstructive pulmonary disease [COPD], cardiovascular diseases, cancer). In the event of any positive answer, a message was displayed recommending the user to consult a physician. In addition, they were asked about smoking cessation intention before and after answering these 13 questions. Finally, incidence of stage 1 or 2 lung cancers diagnosed during the launch period of our application was evaluated by comparing data from various sources to those from the same period during the previous year.ResultsOf the 5671 users who were eligible for evaluation, an alert was sent to the majority (4118/5671, 72.6%), with a higher incidence for current smokers (2833/3679, 77.0% vs 1298/1992, 65.2%; P<.001). The most frequent symptoms triggering the notifications were fatigue (2023/5671, 35.7%), cough (1658/5671, 29.2%), dyspnea (1502/5671, 26.5%), and persistent chest pain (1286/5671, 22.7%). Of the current smokers, 14.0% (515/3679) showed symptoms suggesting COPD, 15.5% (571/3679) showed symptoms suggesting stable angina, 12.4% (455/3679) probably had lower extremity artery disease, and 6.8% (249/3679) had possible cancer. Of the users, 36.5% (1343/3679) claimed that they thought about quitting smoking, and 48.7% (1795/3679) had thought about reducing their consumption. Surgery-eligible stage 1 and 2 lung cancer incidence was 24% (14/58) during the study period versus 9% (5/54) during the previous year in Sarthe county (P=.04), whereas it remained unchanged in the neighboring county of Maine-et-Loire.ConclusionsA majority of current and ex-smokers showed worrying symptoms, and the use of a self-assessment smartphone app may drive a majority of smokers toward the intention of smoking cessation or decreasing consumption. A randomized study should be performed to confirm this intention and to support the potential increase of symptomatic lung cancer detection at early, surgery-accessible stages.Trial RegistrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT04048954","term_id":"NCT04048954"}}NCT04048954; https://www.clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT04048954","term_id":"NCT04048954"}}NCT04048954     

Relationship between Nutritional Status and Clinical Outcome in Patients Treated for Lung Cancer

Background. Between 34.5% and 69% of the patients with lung cancer are at risk of malnutrition. Quality of life (QoL) and physical status assessment provides valuable prognostic data on lung cancer patients. Malnutrition is a prognostic parameter for clinical outcome. Therefore, the identification of significant factors affecting the clinical outcome and QoL is important. The purpose of this study was to evaluate the relationship between nutritional status and outcome, i.e., overall survival, time to tumor progression, and QoL, in lung cancer patients. Materials and methods. We performed a systematic search of the Pubmed/MEDLINE databases per the Cochrane guidelines to conduct a meta-analysis consistent with the PRISMA statement, using the following keywords: “lung cancer,” “malnutrition,” “nutrition,” “quality of life,” “well-being,” “health-related quality of life,” and “outcome.” Out of the 96 papers identified, 12 were included in our meta-analysis. Results. Our meta-analysis shows that patients with a good nutritional status have a better QoL than malnourished patients in the following functioning domains: physical (g = 1.22, 95% CI = 1.19 to 1.46, p < 0.001), role (g = 1.45, 95% CI = 1.31 to 1.59, p < 0.001), emotional (g = 1.10, 95% CI = 0.97 to 1.24, p < 0.001), cognitive (g = 0.91, 95% CI = 0.76 to 1.06, p < 0.001), and social (g = 1.41, 95% CI = 1.27 to 1.56, p < 0.001). The risk of death was significantly higher in malnourished than in well-nourished patients (HR = 1.53, 95% CI = 1.25 to 1.86, p < 0.001). Nutritional status was significantly associated with survival, indicating that patients with a poorer nutritional status are at more risk of relapse. Conclusions. Nutritional status is a significant clinical and prognostic parameter in the assessment of lung cancer treatment. Malnutrition is associated with poorer outcome in terms of overall survival, time to tumor progression, and QoL in patients treated for lung cancer.     

个旧居民肺癌发病率与室内氡关系的探讨

目的 探讨云南个旧地区居民（不包括矿工和冶炼工）肺癌高发的原因。方法 应用固体核径迹探测器（简称SSNTD）方法对土壤、室内氡进行了测定。结果 发现纵贯个旧地区的个旧－小江断裂带提供了丰富的土壤氡的地下来源，在断裂带上测得土壤氡水平为世界土壤氡平均值的8．6倍，断裂带上的室内氡水平是远离断裂带室内氡水平的6．5倍。调查组室内氡平均值比对照组室内氡平均值高出44．5％。分组统计表明，室内氡水平越高，肺癌发病率（除一组例外）相应增高。结论 通过本次调查似乎可以认为肺癌发病率与室内氡水平有呈正相关的趋势。     

电热毯电磁场暴露与女性乳腺癌关系Meta分析

目的综合分析电热毯电磁场暴露与女性乳腺癌之间的关系。方法对国内外发表的关于电热毯电磁场暴露与女性乳腺癌关系的病例对照研究,按纳入和剔除标准严格筛选,采用Meta分析合并文献效应值,并进行一致性检验及发表偏倚检验。结果电热毯电磁场暴露与女性乳腺癌关系的合并OR=1.02(95%CI∶0.95~1.08);使用电热毯方式与乳腺癌无关;绝经前亚组女性电热毯使用与乳腺癌有关(OR=1.18,95%CI∶1.01~1.37),而绝经后亚组女性电热毯使用与乳腺癌无关。结论尚不能认为电热毯电磁场暴露是女性乳腺癌的危险因素。     

南京市人群DNA修复基因XRCC1多态性与肺癌易感性的关系

[目的]研究碱基切除修复基因XRCC1多态性与南京市人群肺癌易感性的关系。[方法]采用配对病例．对照研究，收集南京籍原发性肺癌患者104例为病例组，同时按1：1配对选择非肿瘤、非呼吸道疾病患者104例为对照组，并进行流行病学调查。应用PCR-RFLP方法分析了病例组和对照组的XRCC1基因Arg194Trp和Arg399Gln两个位点的多态性，比较不同基因型与肺癌易感性的关系，以及基因多态性与吸烟之间对肺癌易感性的交互作用。[结果]携带399Gln等位基因的个体其肺癌危险性增高(OR=1．790，95％CI=1．033～3．103，P=0．038)，且主要增加患鳞癌的危险(OR=2．426，95％CI=1．123～5．237，P=0．023)；并与吸烟指数≥20的有一定的协同作用(OR=2．536，95％CI=1．043～6．165)。Arg194Trp与肺癌危险性之间未见显著性相关(0R=1．040，95％CI=0．600～1．805)。[结论]碱基切除修复基因XRCC1的多态性可能会对肺癌易感性产生影响，并可能与吸烟量之间存在一定的协同作用。     

Characteristics Associated with Exposure to and Participation in a Televised Smoking Cessation Intervention Program for Women with High School or Less Education

OBJECTIVES: This paper estimates the prevalence of exposure to and participation in a televised smoking cessation intervention targeting women with high school or less education and describes characteristics related to exposure and participation. METHODS: A random sample of the population of female smokers with high school or less education in the Chicago metropolitan area was used to estimate the prevalence of exposure to a targeted smoking cessation intervention with television and booklet components (n = 722). Multiple logistic regression analysis was used to examine characteristics related to exposure to each component and participation, defined as simultaneous use of both components, in a sample of population and registrants combined (n = 1,727). RESULTS: About one of every four women in the target population either saw the television series or called for the booklet (24.5%); 17.5% saw the television series, 9.4% called for the booklet, and 2.4% both saw the television series and called for the booklet. Independent predictors of booklet exposure were black, older age, annual income $40,000 or less, heavier smoking, and higher stage of readiness to quit. Adjusting for booklet exposure, independent predictors of television exposure were older age and nonblack. Independent predictors of participation were black, older age, and higher stage of readiness to quit. CONCLUSIONS: The intervention reached a substantial portion of low-educated female smokers. Women who were older, black, or at higher stages of readiness to quit were most likely to be exposed and to participate. Heavier smokers or lower income women were most likely to be exposed but not necessarily to participate.