Childhood brain tumour risk and its association with wireless phones: a commentary

Case-control studies on adults point to an increased risk of brain tumours (glioma and acoustic neuroma) associated with the long-term use of mobile phones. Recently, the first study on mobile phone use and the risk of brain tumours in children and adolescents, CEFALO, was published. It has been claimed that this relatively small study yielded reassuring results of no increased risk. We do not agree. We consider that the data contain several indications of increased risk, despite low exposure, short latency period, and limitations in the study design, analyses and interpretation. The information certainly cannot be used as reassuring evidence against an association, for reasons that we discuss in this commentary

Systems biological and mechanistic modelling of radiation-induced cancer

This paper summarises the five presentations at the First International Workshop on Systems Radiation Biology that were concerned with mechanistic models for carcinogenesis. The mathematical description of various hypotheses about the carcinogenic process, and its comparison with available data is an example of systems biology. It promises better understanding of effects at the whole body level based on properties of cells and signalling mechanisms between them. Of these five presentations, three dealt with multistage carcinogenesis within the framework of stochastic multistage clonal expansion models, another presented a deterministic multistage model incorporating chromosomal aberrations and neoplastic transformation, and the last presented a model of DNA double-strand break repair pathways for second breast cancers following radiation therapy

Evaluating the Number of Stages in Development of Squamous Cell and Adenocarcinomas across Cancer Sites Using Human Population-Based Cancer Modeling

BACKGROUND: Adenocarcinomas (ACs) and squamous cell carcinomas (SCCs) differ by clinical and molecular characteristics. We evaluated the characteristics of carcinogenesis by modeling the age patterns of incidence rates of ACs and SCCs of various organs to test whether these characteristics differed between cancer subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Histotype-specific incidence rates of 14 ACs and 12 SCCs from the SEER Registry (1973-2003) were analyzed by fitting several biologically motivated models to observed age patterns. A frailty model with the Weibull baseline was applied to each age pattern to provide the best fit for the majority of cancers. For each cancer, model parameters describing the underlying mechanisms of carcinogenesis including the number of stages occurring during an individual's life and leading to cancer (m-stages) were estimated. For sensitivity analysis, the age-period-cohort model was incorporated into the carcinogenesis model to test the stability of the estimates. For the majority of studied cancers, the numbers of m-stages were similar within each group (i.e., AC and SCC). When cancers of the same organs were compared (i.e., lung, esophagus, and cervix uteri), the number of m-stages were more strongly associated with the AC/SCC subtype than with the organ: 9.79±0.09, 9.93±0.19 and 8.80±0.10 for lung, esophagus, and cervical ACs, compared to 11.41±0.10, 12.86±0.34 and 12.01±0.51 for SCCs of the respective organs (p<0.05 between subtypes). Most SCCs had more than ten m-stages while ACs had fewer than ten m-stages. The sensitivity analyses of the model parameters demonstrated the stability of the obtained estimates. CONCLUSIONS/SIGNIFICANCE: A model containing parameters capable of representing the number of stages of cancer development occurring during individual's life was applied to the large population data on incidence of ACs and SCCs. The model revealed that the number of m-stages differed by cancer subtype being more strongly associated with ACs/SCCs histotype than with organ/site

A Molecular Clock Infers Heterogeneous Tissue Age Among Patients with Barrett's Esophagus

National Institutes of Health (www.nih.gov) and the National Cancer Institute (www.cancer.gov) under grants U01CA182940 (BG-U01) (to EGL, CJW, WDH, WMG, and KC), 5P30CA015704 (to WMG and CJW), 5U01CA152756 (to WMG and CJW), 5U54CA163060 (to AC), and NIH1P50CA150964-01A1 (to JEW

PLoS One

Quantifying the association between lifetime exposures and the risk of developing a chronic disease is a recurrent challenge in epidemiology. Individual exposure trajectories are often heterogeneous and studying their associations with the risk of disease is not straightforward. We propose to use a latent class mixed model (LCMM) to identify profiles (latent classes) of exposure trajectories and estimate their association with the risk of disease. The methodology is applied to study the association between lifetime trajectories of smoking or occupational exposure to asbestos and the risk of lung cancer in males of the ICARE population-based case-control study. Asbestos exposure was assessed using a job exposure matrix. The classes of exposure trajectories were identified using two separate LCMM for smoking and asbestos, and the association between the identified classes and the risk of lung cancer was estimated in a second stage using weighted logistic regression and all subjects. A total of 2026/2610 cases/controls had complete information on both smoking and asbestos exposure, including 1938/1837 cases/controls ever smokers, and 1417/1520 cases/controls ever exposed to asbestos. The LCMM identified four latent classes of smoking trajectories which had different risks of lung cancer, all much stronger than never smokers. The most frequent class had moderate constant intensity over lifetime while the three others had either long-term, distant or recent high intensity. The latter had the strongest risk of lung cancer. We identified five classes of asbestos exposure trajectories which all had higher risk of lung cancer compared to men never occupationally exposed to asbestos, whatever the dose and the timing of exposure. The proposed approach opens new perspectives for the analyses of dose-time-response relationships between protracted exposures and the risk of developing a chronic disease, by providing a complete picture of exposure history in terms of intensity, duration, and timing of exposure

Impact of Reduced Tobacco Smoking on Lung Cancer Mortality in the United States During 1975-2000

Background Considerable effort has been expended on tobacco control strategies in the United States since the mid-1950s. However, we have little quantitative information on how changes in smoking behaviors have impacted lung cancer mortality. We quantified the cumulative impact of changes in smoking behaviors that started in the mid-1950s on lung cancer mortality in the United States over the period 1975-2000. Methods A consortium of six groups of investigators used common inputs consisting of simulated cohort-wise smoking histories for the birth cohorts of 1890 through 1970 and independent models to estimate the number of US lung cancer deaths averted during 1975-2000 as a result of changes in smoking behavior that began in the mid-1950s. We also estimated the number of deaths that could have been averted had tobacco control been completely effective in eliminating smoking after the Surgeon General's Results Approximately 795 851 US lung cancer deaths were averted during the period 1975-2000: 552 574 among men and 243 277 among women. In the year 2000 alone, approximately 70 218 lung cancer deaths were averted: 44 135 among men and 26 083 among women. However, these numbers are estimated to represent approximately 32% of lung cancer deaths that could have potentially been averted during the period 1975-2000, 38% of the lung cancer deaths that could have been averted in 1991-2000, and 44% of Conclusions Our results reflect the cumulative impact of changes in smoking behavior since the 1950s. Despite a large impact of changing smoking behaviors on lung cancer deaths, lung cancer remains a major public health problem. Continued efforts at tobacco control are critical to further reduce the burden of this disease. J Natl Cancer Inst 2012; 104: 541-54

Benefits and Harms of Computed Tomography Lung Cancer Screening Strategies: A Comparative Modeling Study for the US Preventive Services Task Force

Background: The optimum screening policy for lung cancer is unknown. Objective: To identify efficient computed tomography (CT) screening scenarios in which relatively more lung cancer deaths are averted for fewer CT screening examinations. Design: Comparative modeling study using 5 independent models. Data Sources: The National Lung Screening Trial; the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial; the Surveillance, Epidemiology, and End Results program; and the U.S. Smoking History Generator. Target Population: U.S. cohort born in 1950. Time Horizon: Cohort followed from ages 45 to 90 years. Perspective: Societal. Intervention: 576 scenarios with varying eligibility criteria (age, pack-years of smoking, years since quitting) and screening intervals. Outcome Measures: Benefits included lung cancer deaths averted or life-years gained. Harms included CT examinations, false-positive results (including those obtained from biopsy/surgery), overdiagnosed cases, and radiation-related deaths. Results of Best-Case Scenario: The most advantageous strategy was annual screening from ages 55 through 80 years for ever-smokers with a smoking history of at least 30 pack-years and ex-smokers with less than 15 years since quitting. It would lead to 50% (model ranges, 45% to 54%) of cases of cancer being detected at an early stage (stage I/II), 575 screening examinations per lung cancer death averted, a 14% (range, 8.2% to 23.5%) reduction in lung cancer mortality, 497 lung cancer deaths averted, and 5250 life-years gained per the 100 000-member cohort. Harms would include 67 550 false-positive test results, 910 biopsies or surgeries for benign lesions, and 190 overdiagnosed cases of cancer (3.7% of all cases of lung cancer [model ranges, 1.4% to 8.3%]). Results of Sensitivity Analysis: The number of cancer deaths averted for the scenario varied across models between 177 and 862; the number of overdiagnosed cases of cancer varied between 72 and 426. Limitations: Scenarios assumed 100% screening adherence. Data derived from trials with short duration were extrapolated to lifetime follow-up. Conclusion: Annual CT screening for lung cancer has a favorable benefit-harm ratio for individuals aged 55 through 80 years with 30 or more pack-years' exposure to smoking