Ma J, Ward EM, Smith R, Jemal A
Annual number of lung cancer deaths potentially avertable by screening in the United States.
Cancer. 2013; 119(7):1381-5 [PubMed]

BACKGROUND: The National Lung Screening Trial (NLST), which was conducted between 2002 and 2009, demonstrated that screening with low-dose computed tomography (LDCT) reduced lung cancer mortality by 20% among screening-eligible populations compared with chest x-ray. In this article, the authors provide an estimate of the annual number of lung cancer deaths that can be averted by screening, assuming the screening regimens adopted in the NLST are fully implemented in the United States.
METHODS: The annual number of lung cancer deaths that can be averted by screening was estimated as a product of the screening effect, the US population size (obtained from the 2010 US Census data), the prevalence of screening eligibility (estimated using the 2010 National Health Interview Survey [NHIS] data), and the lung cancer mortality rates among screening-eligible populations (estimated using the NHIS data from 2000-2004 and the third National Health and Nutrition Examination Survey linked mortality files). Analyses were performed separately by sex, age, and smoking status, with Poisson regression analysis used for mortality rate estimation. Uncertainty of the estimates of the number of avertable lung cancer deaths was quantified by simulation.
RESULTS: Approximately 8.6 million Americans (95% confidence interval [95% CI], 8.0 million-9.2 million), including 5.2 million men (95% CI, 4.8 million-5.7 million) and 3.4 million women (95% CI, 3.0 million -3.8 million), were eligible for lung cancer screening in 2010. If the screening regimen adopted in the NLST was fully implemented among these screening-eligible US populations, a total of 12,250 (95% CI, 10,170-15,671) lung cancer deaths (8990 deaths in men and 3260 deaths in women) would be averted each year.
CONCLUSIONS: The data from the current study indicate that LDCT screening could potentially avert approximately 12,000 lung cancer deaths per year in the United States. Further studies are needed to estimate the number of avertable lung cancer deaths and the cost-effectiveness of LDCT screening under different scenarios of risk, various screening frequencies, and various screening uptake rates.

Smith RA, Brooks D, Cokkinides V, et al.
Cancer screening in the United States, 2013: a review of current American Cancer Society guidelines, current issues in cancer screening, and new guidance on cervical cancer screening and lung cancer screening.
CA Cancer J Clin. 2013 Mar-Apr; 63(2):88-105 [PubMed]

Each year the American Cancer Society (ACS) publishes a summary of its recommendations for early cancer detection, a report on data and trends in cancer screening rates, and select issues related to cancer screening. In this issue of the journal, current ACS cancer screening guidelines are summarized, as are updated guidelines on cervical cancer screening and lung cancer screening with low-dose helical computed tomography. The latest data on the use of cancer screening from the National Health Interview Survey also are described, as are several issues related to screening coverage under the Patient Protection and Affordable Care Act of 2010.

Karimzadeh L, Koohdani F, Siassi F, et al.
Relation between nitrate and nitrite food habits with lung cancer.
J Exp Ther Oncol. 2012; 10(2):107-12 [PubMed]

Nitrites, a probable human carcinogen, generate reactive nitrogen species that may cause damage to the lung. We evaluated the association between nutritional habits related to nitrite and nitrate intake and risk of lung cancer in Mazandaran, Northern Province of Iran. In this case-control study the two groups were matched for gender and age (+/- 5 years). A semi -quantitative food frequency questionnaire (FFQ) was used to collect dietary data about nutritional habits related to nitrate, nitrite, vitamins E and C intake, from 40 lung cancer cases and 40 control subjects admitted at Mazanaran hospitals. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of lung cancer using logistic regression. Mean score of nutritional habits in case group was significantly lower than that in control group (P less than or equal 0.001). We observed a positive association between animal sources of nitrate and nitrite intake (OR = 2.7, 95% CI: 0.13-0.96) and risk of lung cancer. Decreased risk of lung cancer was also observed with fruit intake (OR = 0.26, 95% CI: 1.3-11). Our results indicate a probable association between nutritional habits related to animal sources of nitrate and nitrite intake and the risk of lung cancer that requires to be confirmed by other studies.

Lantz PM, Mendez D, Philbert MA
Radon, smoking, and lung cancer: the need to refocus radon control policy.
Am J Public Health. 2013; 103(3):443-7 [PubMed]

Exposure to radon is the second leading cause of lung cancer, and the risk is significantly higher for smokers than for nonsmokers. More than 85% of radon-induced lung cancer deaths are among smokers. The most powerful approach for reducing the public health burden of radon is shaped by 2 overarching principles: public communication efforts that promote residential radon testing and remediation will be the most cost effective if they are primarily directed at current and former smokers; and focusing on smoking prevention and cessation is the optimal strategy for reducing radon-induced lung cancer in terms of both public health gains and economic efficiency. Tobacco control policy is the most promising route to the public health goals of radon control policy.

Wender R, Fontham ET, Barrera E, et al.
American Cancer Society lung cancer screening guidelines.
CA Cancer J Clin. 2013 Mar-Apr; 63(2):107-17 [PubMed] Free Access to Full Article

Findings from the National Cancer Institute's National Lung Screening Trial established that lung cancer mortality in specific high-risk groups can be reduced by annual screening with low-dose computed tomography. These findings indicate that the adoption of lung cancer screening could save many lives. Based on the results of the National Lung Screening Trial, the American Cancer Society is issuing an initial guideline for lung cancer screening. This guideline recommends that clinicians with access to high-volume, high-quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30-pack-year smoking history and who currently smoke or have quit within the past 15 years. A process of informed and shared decision-making with a clinician related to the potential benefits, limitations, and harms associated with screening for lung cancer with low-dose computed tomography should occur before any decision is made to initiate lung cancer screening. Smoking cessation counseling remains a high priority for clinical attention in discussions with current smokers, who should be informed of their continuing risk of lung cancer. Screening should not be viewed as an alternative to smoking cessation.

Bunn PA
Worldwide overview of the current status of lung cancer diagnosis and treatment.
Arch Pathol Lab Med. 2012; 136(12):1478-81 [PubMed]

Lung cancer is the leading worldwide cause of cancer deaths. Smoking is the dominant cause of lung cancer and smoking cessation is the established method to reduce lung cancer mortality. While lung cancer risk is reduced in former smokers, they have a lifelong increase in risk, compared to never-smokers. Novel chemoprevention strategies, such as oral or inhaled prostacyclin analogs, hold promise for these subjects. Low-dose spiral computed tomography screening reduced lung cancer mortality by 20% in high-risk heavy smokers older than 50 years. However, the high false-positive rate (96%) means that screened patients required controlled follow-up in experienced centers. An increasing percentage of patients with advanced lung cancer have molecular drivers in genes for which oral tyrosine kinase inhibitors have been developed.

Dragnev K, You M, Wang Y, Lubet R
Lung cancer chemoprevention: difficulties, promise and potential agents?
Expert Opin Investig Drugs. 2013; 22(1):35-47 [PubMed]

INTRODUCTION: In a variety of cancers there is evidence that specific regimens can prevent or significantly delay the development of cancer. Thus, for breast cancer (ER+) use of SERMs or aromatase inhibitors can substantially decrease tumor incidence. For cervical cancer, HPV vaccination will inhibit long term cancer incidence. For colon cancer, the second greatest cancer killer, administration of aspirin and other NSAIDs decreases advanced colon adenomas in Phase II trials and epidemiologic data support their ability to prevent colon cancer. To date prevention trials in the area of lung cancer have shown minimal efficacy. AREAS COVERED: The paper examines and discusses in greater detail certain promising agents which the authors have tested either preclinically and or in early phase clinical trials. These agents include RXR agonists, EGFr inhibitors, NSAIDs and Triterpenoids. Other agents including glucocorticoids, pioglitazone and iloprost are briefly mentioned. In addition, the paper presents various types of potential Phase II lung cancer prevention trials and describes their strengths and weaknesses. The potential use of various biomarkers as endpoints in trials e.g. histopathology, non-specific biomarkers (e.g., Ki67, cyclin D expression, apoptosis) and molecular biomarkers (e.g. specific phosphorylated proteins, gene expression etc.) is presented. Finally, we examine at least one approach, the use of aerosols, which may diminish the systemic toxicity associated with certain of these agents. EXPERT OPINION: The manuscript presents: a) a number of promising agents which appear applicable to further Phase II prevention trials; b) approaches to defining potential preventive agents as well; c) approaches which might mitigate the side effects associated with potential agents most specifically the use of aerosols. Finally, we discuss biomarker studies both preclinical and clinical which might help support potential Phase II trials. The particular appeal to the preclinical studies is that they can be followed to a tumor endpoint. We hope that this will give the reader further background and allow one to appreciate the potential and some of the hurdles associated with lung cancer chemoprevention.

Barry SA, Tammemagi MC, Penek S, et al.
Predictors of adverse smoking outcomes in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.
J Natl Cancer Inst. 2012; 104(21):1647-59 [PubMed] Article available free on PMC after 07/11/2013

BACKGROUND: The impact of lung cancer screening on smoking behavior is unclear. The aims of this ancillary study of the Prostate Lung Colorectal and Ovarian Cancer Screening Trial were to produce risk prediction models to identify individuals at risk of relapse or continued smoking and to evaluate whether cancer-screening variables affect long-term smoking outcomes.
METHODS: Participants completed a baseline questionnaire at trial enrollment and a supplemental questionnaire 4-14 years after enrollment, which assessed several cancer-related variables, including family history of cancer, comorbidities, and tobacco use. Multivariable logistic regression models were used to predict smoking status at completion of the supplemental questionnaire. The models' predictive performances were evaluated by assessing discrimination via the receiver operator characteristic area under the curve (ROC AUC) and calibration. Models were internally validated using bootstrap methods.
RESULTS: Of the 31 694 former smokers on the baseline questionnaire, 1042 (3.3%) had relapsed (ie, reported being a current smoker on the supplemental questionnaire). Of the 6807 current smokers on the baseline questionnaire, 4439 (65.2%) reported continued smoking on the supplemental questionnaire. Relapse was associated with multiple demographic, medical, and tobacco-related characteristics. This model had a bootstrap median ROC AUC of 0.862 (95% confidence interval [CI] = 0.858 to 0.866) and a calibration slope of 1.004 (95% CI = 0.978 to 1.029), indicating excellent discrimination and calibration. Predictors of continued smoking also included multiple demographic, medical, and tobacco-related characteristics. This model had an ROC AUC of 0.611 (95% CI = 0.605 to 0.614) and a slope of 1.006 (95% CI = 0.962 to 1.041), indicating modest discrimination. Neither the trial arm nor the lung-screening result was statistically significantly associated with smoking outcomes.
CONCLUSION: These models, if validated externally, may have public health utility in identifying individuals at risk for adverse smoking outcomes, who may benefit from relapse prevention and smoking cessation interventions.

Yang G, Shu XO, Chow WH, et al.
Soy food intake and risk of lung cancer: evidence from the Shanghai Women's Health Study and a meta-analysis.
Am J Epidemiol. 2012; 176(10):846-55 [PubMed] Article available free on PMC after 15/11/2013

The authors prospectively evaluated the association of soy food intake with lung cancer risk, overall and by tumor aggressiveness, and performed a meta-analysis of published data. Included in the analysis were 71,550 women recruited into the Shanghai Women's Health Study (Shanghai, China) in 1997-2000. Usual soy food intake was assessed at baseline and reassessed during follow-up through in-person interviews. During a mean follow-up period of 9.1 years, 370 incident lung cancer cases were identified; 340 patients were lifetime never smokers. After adjustment for potential confounders, soy food intake was inversely associated with subsequent risk of lung cancer (P(trend) = 0.004); the hazard ratio for the highest quintile of intake compared with the lowest was 0.63 (95% confidence interval: 0.44, 0.90). This inverse association appeared predominately among women with later age at menopause (P(interaction) = 0.01) and for aggressive lung cancer as defined by length of survival (<12 months vs. ≥12 months; P(heterogeneity) = 0.057). Meta-analysis of 7 studies conducted among nonsmokers found a summary relative risk of 0.59 (95% confidence interval: 0.49, 0.71) for the highest categories of soy or isoflavone intake versus the lowest. This study suggests that soy food consumption may reduce lung cancer risk in nonsmoking women, particularly for aggressive tumors, and its effect may be modified by endogenous estrogens.

Cortés-Jofré M, Rueda JR, Corsini-Muñoz G, et al.
Drugs for preventing lung cancer in healthy people.
Cochrane Database Syst Rev. 2012; 10:CD002141 [PubMed]

BACKGROUND: This is an updated version of the original review published in Issue 2, 2003. Some studies have suggested a protective effect of antioxidant nutrients on lung cancer. Observational epidemiological studies suggest an association between higher dietary levels of fruits and vegetables containing beta-carotene and a lower risk of lung cancer.
OBJECTIVES: To determine whether vitamins, minerals and other potential agents, alone or in combination, reduce incidence and mortality from lung cancer in healthy people.
SEARCH METHODS: For this update we have used a search strategy adapted from the design in the original review. The following electronic databases have been searched up to December 2011: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). References included in published studies and reviews were also screened.
SELECTION CRITERIA: Included studies were randomised controlled clinical trials comparing different vitamins, mineral supplements or supplements with placebo, administered to healthy people with the aim of preventing lung cancer.
DATA COLLECTION AND ANALYSIS: Two authors independently selected the trials to be included in the review, assessed the methodological quality of each trial and extracted data using a standardised form. For each study, relative risk and 95% confidence limits were calculated for dichotomous outcomes and pooled results were calculated using the random-effect model.
MAIN RESULTS: In the first version of this review four studies were included; in this review update, an additional five studies have been included. Four studies included only males and two only females; two studies included only participants considered at high risk, namely smokers or exposed to asbestos, and one study included people deficient in many micronutrients. Six studies analysed vitamin A, three vitamin C, four vitamin E, one selenium supplements, and six studied combinations of two or more products. All the RCTs included in this review were classified as being of low risk of bias.For people not at high risk of lung cancer and compared to placebo, none of the supplements of vitamins or minerals or their combinations resulted in a statistically significant difference in lung cancer incidence or mortality, except for a single study that included 7627 women and found a higher risk of lung cancer incidence for those taking vitamin C but not for total cancer incidence, but that effect was not seen in males or when the results for males and females were pooled.For people at high risk of lung cancer, such as smokers and those exposed to asbestos and compared to placebo, beta-carotene intake showed a small but statistically significant higher risk of lung cancer incidence, lung cancer mortality and for all-causes mortality.
AUTHORS' CONCLUSIONS: There is no evidence for recommending supplements of vitamins A, C, E, selenium, either alone or in different combinations, for the prevention of lung cancer and lung cancer mortality in healthy people. There is some evidence that the use of beta-carotene supplements could be associated with a small increase in lung cancer incidence and mortality in smokers or persons exposed to asbestos.

Gray JE, Altiok S, Alexandrow MG, et al.
Phase 2 randomized study of enzastaurin (LY317615) for lung cancer prevention in former smokers.
Cancer. 2013; 119(5):1023-32 [PubMed] Article available free on PMC after 01/03/2014

BACKGROUND: Chemoprevention for lung cancer with nutraceutical or anti-inflammatory agents has had mixed clinical benefit. Novel targeted agents hold the promise of greater efficacy and selectivity. The authors of this report evaluated enzastaurin, a selective protein kinase C-β (PKC-β) inhibitor with antiproliferative and proapoptotic properties, in former smokers.
METHODS: The primary objective of this study was to compare the average fraction of Ki-67-stained cells (the Ki-67 labeling index [LI]) in bronchial biopsy specimens that were collected before and after treatment. Participants were randomized (2:1) to receive either 6 months of daily oral enzastaurin (500 mg) or placebo. Stratification was based on morphology, history of lung cancer, and airway obstruction.
RESULTS: In pretrial investigations, the rationale for PKC-β inhibition and pathway interrogation was established in premalignant lesions and early stage lung cancer. In an intent-to-treat analysis, of 40 randomized participants, there was no significant difference in the pretreatment/post-treatment change in the Ki-67 LI between the enzastaurin group and the placebo group (P = .53). Six participants discontinued enzastaurin, including 4 participants who had adverse events, including abdominal distension, deep vein thrombosis, hyponatremia, and rash, and 2 participants who decided to discontinue. One participant in the placebo group was discontinued on the study because of noncompliance. Two participants had ≥1 serious adverse event (bradycardia, deep vein thrombosis, and hypotension).
CONCLUSIONS: To the authors' knowledge, this represents the first chemoprevention trial with a non-US Food and Drug Administration-approved, oral, small-molecule-targeted agent. Although the primary endpoint was not met, enzastaurin was tolerable for 6 months by 75% of participants, and there was a suggestion of response in a subset analysis that was restricted to those who had metaplastic or dysplastic lesions.

Sagawa M, Nakayama T, Tanaka M, et al.
A randomized controlled trial on the efficacy of thoracic CT screening for lung cancer in non-smokers and smokers of <30 pack-years aged 50-64 years (JECS study): research design.
Jpn J Clin Oncol. 2012; 42(12):1219-21 [PubMed]

In order to assess the efficacy of lung cancer screening using low-dose thoracic computed tomography, compared with chest roentgenography, in people aged 50-64 years with a smoking history of <30 pack-years, a randomized controlled trial is being conducted in Japan. The screening methods are randomly assigned individually. The duration of this trial is 10 years. In the intervention arm, low-dose thoracic computed tomography is performed for each participant in the first and the sixth years. In the control arm, chest roentgenography is performed for each participant in the first year. The participants in both arms are also encouraged to receive routine lung cancer screening using chest roentgenography annually. The interpretation of radiological findings and the follow-up of undiagnosed nodules are to be carried out according to the guidelines published in Japan. The required sample size is calculated to be 17 500 subjects for each arm.

Corrales L, Ajona D, Rafail S, et al.
Anaphylatoxin C5a creates a favorable microenvironment for lung cancer progression.
J Immunol. 2012; 189(9):4674-83 [PubMed] Article available free on PMC after 01/11/2013

The complement system contributes to various immune and inflammatory diseases, including cancer. In this study, we investigated the capacity of lung cancer cells to activate complement and characterized the consequences of complement activation on tumor progression. We focused our study on the production and role of the anaphylatoxin C5a, a potent immune mediator generated after complement activation. We first measured the capacity of lung cancer cell lines to deposit C5 and release C5a. C5 deposition, after incubation with normal human serum, was higher in lung cancer cell lines than in nonmalignant bronchial epithelial cells. Notably, lung malignant cells produced complement C5a even in the absence of serum. We also found a significant increase of C5a in plasma from patients with non-small cell lung cancer, suggesting that the local production of C5a is followed by its systemic diffusion. The contribution of C5a to lung cancer growth in vivo was evaluated in the Lewis lung cancer model. Syngeneic tumors of 3LL cells grew slower in mice treated with an antagonist of the C5a receptor. C5a did not modify 3LL cell proliferation in vitro but induced endothelial cell chemotaxis and blood-vessels formation. C5a also contributed to the immunosuppressive microenvironment required for tumor growth. In particular, blockade of C5a receptor significantly reduced myeloid-derived suppressor cells and immunomodulators ARG1, CTLA-4, IL-6, IL-10, LAG3, and PDL1 (B7H1). In conclusion, lung cancer cells have the capacity to generate C5a, a molecule that creates a favorable tumor microenvironment for lung cancer progression.

Courtice MN, Lin S, Wang X
An updated review on asbestos and related diseases in China.
Int J Occup Environ Health. 2012 Jul-Sep; 18(3):247-53 [PubMed]

BACKGROUND: Asbestos is an industrial mineral that can cause diseases such as asbestosis, lung cancer, and mesothelioma. Asbestos consumption in China has increased steadily since the 1960s and is currently at half a million tonnes per year. Work conditions in the asbestos-related industries are poor and exposure levels frequently exceed the occupational exposure limit.
OBJECTIVE: To provide an updated overview on asbestos production and consumption in China and discuss what is known about the resulting burden of asbestos-related diseases.
FINDINGS: China is the world's top chrysotile consumer and second largest producer. Over a million people may be occupationally exposed, yet reliable disease statistics are unavailable and the national burden of asbestos-related disease (ARD) is not well known. Nevertheless, ARD prevalence, incidence, and mortality are expected to be high and will increase for many decades due to the volume of asbestos consumed historically, and a long latency period.
CONCLUSIONS: Government policies to prevent ARD have been implemented but more actions are necessary to ensure compliance and ultimately, the complete elimination of asbestos to prevent a heavy future disease burden.

Sætterstrøm B, Kruse M, Brønnum-Hansen H, et al.
A method to assess the potential effects of air pollution mitigation on healthcare costs.
J Environ Public Health. 2012; 2012:935825 [PubMed] Article available free on PMC after 01/11/2013

OBJECTIVE: The aim of this study was to develop a method to assess the potential effects of air pollution mitigation on healthcare costs and to apply this method to assess the potential savings related to a reduction in fine particle matter in Denmark.
METHODS: The effects of air pollution on health were used to identify "exposed" individuals (i.e., cases). Coronary heart disease, stroke, chronic obstructive pulmonary disease, and lung cancer were considered to be associated with air pollution. We used propensity score matching, two-part estimation, and Lin's method to estimate healthcare costs. Subsequently, we multiplied the number of saved cases due to mitigation with the healthcare costs to arrive to an expression for healthcare cost savings.
RESULTS: The potential cost saving in the healthcare system arising from a modelled reduction in air pollution was estimated at €0.1-2.6 million per 100,000 inhabitants for the four diseases.
CONCLUSION: We have illustrated an application of a method to assess the potential changes in healthcare costs due to a reduction in air pollution. The method relies on a large volume of administrative data and combines a number of established methods for epidemiological analysis.

de Groot P, Munden RF
Lung cancer epidemiology, risk factors, and prevention.
Radiol Clin North Am. 2012; 50(5):863-76 [PubMed]

The greatest risk by far for developing lung cancer is cigarette smoking, but age, radon exposure, environmental pollution, occupational exposures, gender, race, and pre-existing lung disease also are important contributors. However, not all people with these risk factors develop lung cancer, and some without any known risk factor do, indicating the importance of genetic influences. Future advances in understanding and treating lung cancer will be based on genetic analysis. The most effective preventive measure is to never start or to stop cigarette smoking.

Wang Y, Yu X, Wu Y, Zhang D
Coffee and tea consumption and risk of lung cancer: a dose-response analysis of observational studies.
Lung Cancer. 2012; 78(2):169-70 [PubMed]

Results from the recent meta-analysis suggested a favorable effect of green tea consumption and risk of lung cancer, while no significant association was found between black tea consumption and risk of lung cancer. Besides, a significantly positive association was found between coffee consumption and risk of lung cancer. However, the relationship of green tea and coffee consumption is unclear. Thus the dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression. Results suggested that a linear dose-response relationship exists between coffee consumption and risk of lung cancer, while the dose-response relationship is nonlinear between green tea consumption and risk of lung cancer.

Bodmer M, Becker C, Jick SS, Meier CR
Metformin does not alter the risk of lung cancer: a case-control analysis.
Lung Cancer. 2012; 78(2):133-7 [PubMed]

BACKGROUND: Metformin use has been linked to a decreased cancer risk. We explored the association between use of metformin or other antidiabetic drugs and the risk of lung cancer.
METHODS: We assessed the association between metformin, and other antidiabetic drugs and lung cancer using a case-control analysis in the UK-based General Practice Research Database (GPRD). Cases were people with an incident diagnosis of lung cancer. Up to 6 controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the GPRD. The contribution of potential confounders including tuberculosis, chronic obstructive pulmonary disease (COPD), diabetes mellitus, and co-morbid conditions to diabetes was evaluated in univariate models, and final results were adjusted for BMI and smoking.
RESULTS: Long-term use (≥40 prescriptions) of metformin was not associated with an altered risk of lung cancer (adj. OR 1.21, 95% CI 0.97-1.50. Long-term use of sulfonylureas was linked to a marginally decreased risk of lung cancer (adj. OR 0.74, 95% CI 0.60-0.90. This risk decrease was observed in men (adj. OR 0.64, 95% CI 0.50-0.83) but not in women (adj. OR 0.97, 95% CI 0.69-1.37) and this risk decrease was not statistically significant in an analysis restricted to diabetic patients only (adj. OR. 0.82, 95% CI 0.65-1.02). Long-term use of insulin was associated with a slightly increased risk of lung cancer (adj. OR 1.33, 95% CI 1.04-1.71); however, no consistent trend across duration strata was observed.
CONCLUSION: Metformin did not decrease the risk of lung cancer.

Smith SM, Murchie P, Devereux G, et al.
Developing a complex intervention to reduce time to presentation with symptoms of lung cancer.
Br J Gen Pract. 2012; 62(602):e605-15 [PubMed] Article available free on PMC after 01/09/2013

BACKGROUND: Lung cancer is the commonest cause of cancer in Scotland and is usually advanced at diagnosis. Median time between symptom onset and consultation is 14 weeks, so an intervention to prompt earlier presentation could support earlier diagnosis and enable curative treatment in more cases.
AIM: To develop and optimise an intervention to reduce the time between onset and first consultation with symptoms that might indicate lung cancer.
DESIGN AND SETTING: Iterative development of complex healthcare intervention according to the MRC Framework conducted in Northeast Scotland.
METHOD: The study produced a complex intervention to promote early presentation of lung cancer symptoms. An expert multidisciplinary group developed the first draft of the intervention based on theory and existing evidence. This was refined following focus groups with health professionals and high-risk patients.
RESULTS: First draft intervention components included: information communicated persuasively, demonstrations of early consultation and its benefits, behaviour change techniques, and involvement of spouses/partners. Focus groups identified patient engagement, achieving behavioural change, and conflict at the patient-general practice interface as challenges and measures were incorporated to tackle these. Final intervention delivery included a detailed self-help manual and extended consultation with a trained research nurse at which specific action plans were devised.
CONCLUSION: The study has developed an intervention that appeals to patients and health professionals and has theoretical potential for benefit. Now it requires evaluation.

Feuer EJ, Levy DT, McCarthy WJ
Chapter 1:The impact of the reduction in tobacco smoking on U.S. lung cancer mortality, 1975-2000: an introduction to the problem.
Risk Anal. 2012; 32 Suppl 1:S6-S13 [PubMed]

To better understand the contribution of cigarette smoking, and its changing role in lung cancer, this article provides an introduction to a special issue of Risk Analysis, which considers the relationship between smoking and lung cancer death rates during the period 1975-2000 for U.S. men and women aged 30-84 years. Six models are employed, which are part of a consortium of lung cancer modelers funded by National Cancer Institute's Cancer Intervention and Surveillance Modeling Network (CISNET). Starting with birth-cohort-specific smoking histories derived from National Health Interview Surveys, three scenarios are modeled: Actual Tobacco Control (observed trends in smoking), Complete Tobacco Control (a counterfactual lower bound on smoking rates that could have been achieved had all smoking ceased after the first Surgeon General's report in 1964), and No Tobacco Control (a counterfactual upper bound on smoking rates if smoking patterns that prevailed before the first studies in the 1950s began to inform the public about the hazards of smoking). Using these three scenarios and the lung cancer models, the number and percentage of lung cancer deaths averted from 1975-2000, among all deaths that could have been averted if tobacco control efforts been immediate and perfect, can be estimated. The variability of the results across multiple models provides a measure of the robustness of the results to model assumptions and structure. The results provide not only a portrait of the achieved impact of tobacco control on lung cancer mortality, but also the bounds of what still needs to be achieved.

Jeon J, Meza R, Krapcho M, et al.
Chapter 5: Actual and counterfactual smoking prevalence rates in the U.S. population via microsimulation.
Risk Anal. 2012; 32 Suppl 1:S51-68 [PubMed] Article available free on PMC after 01/07/2013

The smoking history generator (SHG) developed by the National Cancer Institute simulates individual life/smoking histories that serve as inputs for the Cancer Intervention and Surveillance Modeling Network (CISNET) lung cancer models. In this chapter, we review the SHG inputs, describe its outputs, and outline the methodology behind it. As an example, we use the SHG to simulate individual life histories for individuals born between 1890 and 1984 for each of the CISNET smoking scenarios and use those simulated histories to compute the corresponding smoking prevalence over the period 1975-2000.

Holford TR, Clark L
Chapter 4: Development of the counterfactual smoking histories used to assess the effects of tobacco control.
Risk Anal. 2012; 32 Suppl 1:S39-50 [PubMed] Article available free on PMC after 01/07/2013

Publication of the Surgeon General's Report in 1964 marshaled evidence of the harm to public health caused by cigarette smoking, including lung cancer mortality, and provided an impetus for introducing control programs. The purpose of this article is to develop estimates of their effect on basic smoking exposure input parameters related to introduction of the report. Fundamental inputs used to generate exposure to cigarettes are initiation and cessation rates for men and women, as well as the distribution of the number of cigarettes smoked per day. These fundamental quantities are presented for three scenarios: actual tobacco control in the United States; no tobacco control in which the experience before 1955 was assumed to continue; and complete tobacco control in which all smoking ceased following publication of the report. These results were derived using data from National Health Interview Surveys, and they provide basic input parameters for the Smoking History Generator used by each of the lung cancer models developed by the Cancer Intervention and Surveillance Modeling Network.

Boer R, Moolgavkar SH, Levy DT
Chapter 15: Impact of tobacco control on lung cancer mortality in the United States over the period 1975-2000--summary and limitations.
Risk Anal. 2012; 32 Suppl 1:S190-201 [PubMed] Article available free on PMC after 01/07/2013

BACKGROUND: A consortium of six research groups estimated the impact on lung cancer mortality of changes in smoking behavior that began around the publication of the Surgeon General's report (SGR). This chapter presents the results of that effort. We quantified the cumulative impact of changes in smoking behaviors on lung cancer mortality in the United States over the period 1975-2000.
METHODS: The six groups used common inputs and independent models to estimate the number of U.S. lung cancer deaths averted over the period 1975-2000 as a result of changes in smoking behavior beginning in the mid fifties, and the number of deaths that could have been averted if tobacco control had completely eliminated all smoking following issuance of the first SGR on Smoking and Health in 1964.
RESULTS: Approximately 795,000 deaths (550,000 men and 245,000 women) were averted over the period 1975-2000 as a result of changes in smoking behavior since in 1950s. In the year 2000 alone approximately 70,000 lung cancer deaths were averted (44,000 among men and 26,000 among women). However, these represent approximately 30% of lung cancer deaths that could have potentially been averted over the period 1975-2000 if smoking was eliminated completely. In the 10-year period 1991-2000, this fraction increased to about 37%.
CONCLUSIONS: Our results show the substantial impact of changes in smoking behavior since the 1950s. Despite a major impact of changing smoking behaviors, tobacco control effort are still needed to further reduce the burden of this disease.

McMahon PM, Kong CY, Johnson BE, et al.
Chapter 9: The MGH-HMS lung cancer policy model: tobacco control versus screening.
Risk Anal. 2012; 32 Suppl 1:S117-24 [PubMed] Article available free on PMC after 01/07/2013

The natural history model underlying the MGH Lung Cancer Policy Model (LCPM) does not include the two-stage clonal expansion model employed in other CISNET lung models. We used the LCPM to predict numbers of U.S. lung cancer deaths for ages 30-84 between 1975 and 2000 under four scenarios as part of the comparative modeling analysis described in this issue. The LCPM is a comprehensive microsimulation model of lung cancer development, progression, detection, treatment, and survival. Individual-level patient histories are aggregated to estimate cohort or population-level outcomes. Lung cancer states are defined according to underlying disease variables, test results, and clinical events. By simulating detailed clinical procedures, the LCPM can predict benefits and harms attributable to a variety of patient management practices, including annual screening programs. Under the scenario of observed smoking patterns, predicted numbers of deaths from the calibrated LCPM were within 2% of observed over all years (1975-2000). The LCPM estimated that historical tobacco control policies achieved 28.6% (25.2% in men, 30.5% in women) of the potential reduction in U.S. lung cancer deaths had smoking had been eliminated entirely. The hypothetical adoption in 1975 of annual helical CT screening of all persons aged 55-74 with at least 30 pack-years of cigarette exposure to historical tobacco control would have yielded a proportion realized of 39.0% (42.0% in men, 33.3% in women). The adoption of annual screening would have prevented less than half as many lung cancer deaths as the elimination of cigarette smoking.

Bloch M, Backinger CL, Compton WM, Conway K
Standing on the threshold of change.
Risk Anal. 2012; 32 Suppl 1:S1-5 [PubMed]

Tobacco use remains the nation's leading cause of preventable premature mortality. Lung cancer, one of the many cancers caused by tobacco use, is both the leading cause of cancer death in the United States and the leading cause of male cancer death globally. This special issue of Risk Analysis features the work of the National Cancer Institute's Cancer Intervention and Surveillance Modeling Network (CISNET), which finds that changes in Americans' smoking behaviors that began in the mid 1950s averted nearly 800,000 U.S. lung cancer deaths in the period 1975-2000 alone. However, this figure represents only about 30% of the lung cancer deaths that could potentially have been averted during this period. Despite dramatic declines in smoking prevalence since the mid 1960s, tobacco use is still far too common; today about one in five American adults smokes cigarettes. The tobacco industry's role in promoting tobacco use is now well documented and, as noted by the President's Cancer Panel, "can no more be ignored in seeking solutions to the tobacco problem than mosquitoes can be ignored in seeking to eradicate malaria." Recent developments, including the passage of legislation granting the Food and Drug Administration broad authority to regulate tobacco products, and the entry into force of the Framework Convention on Tobacco Control, an evidence-based treaty developed by the World Health Organization, hold great promise to more swiftly end the epidemic of lung cancer and other tobacco-caused diseases that exacts such a heavy toll in human suffering in the United States and around the world.

Wang J, Meisenberg O, Chen YH, et al.
Mitigation of thoron exposure by application of wallpaper as a diffusion barrier.
Radiat Prot Dosimetry. 2012; 152(1-3):94-7 [PubMed]

Increasing attention has been paid in recent years to the radioactive gas thoron ((220)Rn), which can cause a significant exposure and increase of lung cancer risk in some regions worldwide. Some experiments were designed to examine whether different types of wall decoration in the room, from ordinary newsprint to commercial wallpaper, can mitigate the concentrations of indoor thoron decay products. Decoration with coated paper was very effective in decreasing the thoron decay products concentration, thus reducing the effective dose by 90 %, while newsprint decoration, which is common in many rural parts of the world, was found to have a smaller but still significant effect in reducing the thoron decay products concentration when applied to the same house.

Lee NJ, Choi DY, Song JK, et al.
Deficiency of C-C chemokine receptor 5 suppresses tumor development via inactivation of NF-κB and inhibition of monocyte chemoattractant protein-1 in urethane-induced lung tumor model.
Carcinogenesis. 2012; 33(12):2520-8 [PubMed]

To evaluate the significance of C-C chemokine receptor type 5 (CCR5) in lung tumor development, we compared carcinogen-induced tumor growth in CCR5 knockout (CCR5(-/-)) mice and wild-type (CCR5(+/+)) mice. CCR5(-/-) mice showed reduced urethane (1g/kg)-induced tumor incidence when compared with those of CCR5(+/+) mice. We investigated the activation of nuclear factor-kappaB/STAT3 since these are implicated transcription factors in the regulation of genes involving tumor growth. Significant inhibition of DNA-binding activity of nuclear factor-kappaB and STAT3, and the translocation of p50 and p65 into the nucleus and the phosphorylation of IĸB were found in the lungs of CCR5(-/-) mice compared with the lungs of CCR5(+/+) mice. Expression of apoptotic protein such as cleaved caspase-3, cleaved PARP and Bax was elevated, whereas the expression levels of survival protein such as Bcl-2 and cIAP1 was decreased in the lungs of CCR5(-/-) mice. Interestingly, we found that the level of monocyte chemoattractant protein-1 (MCP-1), a tumor growth-promoting cytokine, was significantly reduced in the lung tumor tissue and blood of CCR5(-/-) mice compared with the level in CCR5(+/+) mice. In addition, CCR5 small interfering RNA (siRNA) and inhibitor of MCP-1 blocked lung cancer cell growth, which was abolished by the addition of MCP-1 protein in cultured lung cancer cells. Moreover, inactivation of CD8(+) cytotoxic T cell and dendritic cells was significantly increased in the blood, lung tumors and spleens of CCR5(-/-) mice compared with that of CCR5(+/+) mice. Therefore, these results showed that CCR5 deficiency suppressed lung tumor development through the inhibition of nuclear factor-kappaB/STAT3 pathways and the downregulation of MCP-1 in the carcinogen-induced lung tumor model.

Henderson SB, Kosatsky T, Barn P
How to ensure that national radon survey results are useful for public health practice.
Can J Public Health. 2012 May-Jun; 103(3):231-4 [PubMed]

Exposure to radon gas increases the risk of lung cancer. Preliminary national survey data collected by Health Canada indicate that approximately 10% of households exceed the recommended federal long-term guideline of 200 Bq/m3. However, results to date have been reported for large geographic areas in broad measurement categories. Given that Health Canada recommends the most rapid remediation for buildings with the highest concentrations, such reporting makes it challenging for public health authorities to target interventions to communities at the highest risk. Here we use data from a survey in British Columbia to illustrate how improved spatial resolution and more refined concentration categories would be valuable for prioritizing the use of limited public health resources. We encourage Health Canada in future to provide more specific, community-level information that can be used to inform local policy and to engage building owners in radon testing and remediation.

Heuvers ME, Wisnivesky J, Stricker BH, Aerts JG
Generalizability of results from the National Lung Screening Trial.
Eur J Epidemiol. 2012; 27(9):669-72 [PubMed]

Lung cancer is the major cause of cancer-related death worldwide, with a 5-year survival of only 16%. Most lung cancer cases are diagnosed at an advanced incurable stage. As earlier stages have a better prognosis, the key to reducing mortality could be early diagnosis of the disease. At present, low-dose computed tomographic (CT) screening has shown promising data. Lung cancer death rates were reduced by 20% when CT screening is compared to chest radiography in a high-risk group. There are many advantages of CT screening in lung cancer, however there are also some important issues that should be taken into account. Therefore, the applicability of the results to clinical practice is not clear yet. In this Commentary we discuss different aspects that play important roles in the balance between harms and benefits of screening, including overdiagnosis, availability of treatment options worldwide, ethical considerations, costs, and prolonged life expectancy. We conclude that clinicians should be cautious in generalizing findings to the total population of smokers and take into account that the use of lung cancer screening in clinical practice may have limitations.

Liu W, Tan X, Shu L, et al.
Ursolic acid inhibits cigarette smoke extract-induced human bronchial epithelial cell injury and prevents development of lung cancer.
Molecules. 2012; 17(8):9104-15 [PubMed]

Cigarette smoking is the main cause of chronic obstructive pulmonary disease and lung cancer. The present study was aimed to explore the chemopreventive effect of ursolic acid (UA) on these diseases. In the CSE treated normal human bronchial epithelial cell model, UA alleviated cytotoxicity caused by CSE, recovered the intracellular redox balance, and relieved the stimulation of external deleterious factors as well. UA mitigated CSE-induced DNA damage through the Nrf2 (nuclear factor erythroid 2-related factor 2) pathway. Moreover, UA inhibited lung cancer development in the model established by A549 cells in nude mice in vivo. For the first time, our results indicate that UA could be developed as a potential lung cancer chemopreventive agent.