Studies Of Lung Cancer Risk Research Articles

Integrating Electronic Health Record, Cancer Registry, and Geospatial Data to Study Lung Cancer in Asian American, Native Hawaiian, and Pacific Islander Ethnic Groups.

A relatively high proportion of Asian American, Native Hawaiian, and Pacific Islander (AANHPI) females with lung cancer have never smoked. We used an integrative data approach to assemble a large-scale cohort to study lung cancer risk among AANHPIs by smoking status with attention to representation of specific AANHPI ethnic groups. We leveraged electronic health records (EHRs) from two healthcare systems-Sutter Health in northern California and Kaiser Permanente Hawai'i-that have high representation of AANHPI populations. We linked EHR data on lung cancer risk factors (i.e., smoking, lung diseases, infections, reproductive factors, and body size) to data on incident lung cancer diagnoses from statewide population-based cancer registries of California and Hawai'i for the period between 2000 and 2013. Geocoded address data were linked to data on neighborhood contextual factors and regional air pollutants. The dataset comprises over 2.2 million adult females and males of any race/ethnicity. Over 250,000 are AANHPI females (19.6% of the female study population). Smoking status is available for over 95% of individuals. The dataset includes 7,274 lung cancer cases, including 613 cases among AANHPI females. Prevalence of never-smoking status varied greatly among AANHPI females with incident lung cancer, from 85.7% among Asian Indian to 14.4% among Native Hawaiian females. We have developed a large, multilevel dataset particularly well-suited to conduct prospective studies of lung cancer risk among AANHPI females who never smoked. The integrative data approach is an effective way to conduct cancer research assessing multilevel factors on cancer outcomes among small populations.

Lung Cancer Risk and Low (≤50 μg/L) Drinking Water Arsenic Levels for US Counties (2009⁻2013)-A Negative Association.

While epidemiologic studies clearly demonstrate drinking water with high levels of arsenic as a significant risk factor for lung cancer, the evidence at low levels (≤50 μg/L) is uncertain. Therefore, we have conducted an ecological analysis of recent lung cancer incidence for US counties with a groundwater supply of <50 μg/L, the historical limit for both the EPA and WHO. Data sources used included USGS for arsenic exposure, NCI for lung cancer outcome, and CDC and US Census Bureau forcovariates. Poisson log-linear models were conducted for male, female, and total populations using for exposure median county arsenic level, maximum arsenic level ≤50 μg/L, and ≥80% population groundwater dependency. Statistically significant negative associations were found in each of the six models in which the exposure was limited to those who had major exposure (≥80% dependency) to low-levels of arsenic (≤50 μg/L). This is the first large ecological study of lung cancer risk from drinking water arsenic levels that specifically examined the dose-response slope for populations whose exposure was below the historical limit of ≤50 μg/L. The models for each of the three populations (total; male; female) demonstrated an association that is both negative and statistically significant.

Correction of odds ratios in case-control studies for exposure misclassification with partial knowledge of the degree of agreement among experts who assessed exposures

ObjectivesEstimates of association between exposures and diseases are often distorted by error in exposure classification. When the validity of exposure assessment is known, this can be used to adjust these...

Chromosome 15q25 (CHRNA3-CHRNA5) Variation Impacts Indirectly on Lung Cancer Risk

Genetic variants at the 15q25 CHRNA5-CHRNA3 locus have been shown to influence lung cancer risk however there is controversy as to whether variants have a direct carcinogenic effect on lung cancer risk or impact indirectly through smoking behavior. We have performed a detailed analysis of the 15q25 risk variants rs12914385 and rs8042374 with smoking behavior and lung cancer risk in 4,343 lung cancer cases and 1,479 controls from the Genetic Lung Cancer Predisposition Study (GELCAPS). A strong association between rs12914385 and rs8042374, and lung cancer risk was shown, odds ratios (OR) were 1.44, (95% confidence interval (CI): 1.29–1.62, P = 3.69×10−10) and 1.35 (95% CI: 1.18–1.55, P = 9.99×10−6) respectively. Each copy of risk alleles at rs12914385 and rs8042374 was associated with increased cigarette consumption of 1.0 and 0.9 cigarettes per day (CPD) (P = 5.18×10−5 and P = 5.65×10−3). These genetically determined modest differences in smoking behavior can be shown to be sufficient to account for the 15q25 association with lung cancer risk. To further verify the indirect effect of 15q25 on the risk, we restricted our analysis of lung cancer risk to never-smokers and conducted a meta-analysis of previously published studies of lung cancer risk in never-smokers. Never-smoker studies published in English were ascertained from PubMed stipulating - lung cancer, risk, genome-wide association, candidate genes. Our study and five previously published studies provided data on 2,405 never-smoker lung cancer cases and 7,622 controls. In the pooled analysis no association has been found between the 15q25 variation and lung cancer risk (OR = 1.09, 95% CI: 0.94–1.28). This study affirms the 15q25 association with smoking and is consistent with an indirect link between genotype and lung cancer risk.

Absence of radiographic asbestosis and the risk of lung cancer among asbestos‐cement workers: Extended follow‐up of a cohort

It has been a matter of controversy whether there is an increased risk of lung cancer among asbestos-exposed workers without radiographic asbestosis. A previous study of lung cancer risk among asbestos-cement workers has been updated with an additional 12 years of follow-up. Subjects had received radiographic examination at 20 and 25 years from first exposure to asbestos. Radiographs were interpreted by a single National Institute of Safety and Health (NIOSH)-certified B-reader using the 1971 International Labor Office (ILO) Classification of the pneumoconioses as reference standard. Asbestosis was defined as an ILO coding of 1/0 or higher. Standardized Mortality Ratios (SMRs) were calculated using the general population of Ontario as reference. Among asbestos-cement workers without radiographic asbestosis at 20 years latency the lung cancer SMR was 3.84 (2.24-6.14). Among workers without asbestosis when examined at 25 years latency the SMR was 3.69 (1.59-7.26). Workers from an Ontario asbestos-cement factory who did not have radiographic asbestosis at 20 or 25 years from first exposure to asbestos continued to have an increased risk of death from lung cancer during an additional 12 years of follow-up.

Threshold regression for survival data with time‐varying covariates

Time-to-event data with time-varying covariates pose an interesting challenge for statistical modeling and inference, especially where the data require a regression structure but are not consistent with the proportional hazard assumption. Threshold regression (TR) is a relatively new methodology based on the concept that degradation or deterioration of a subject's health follows a stochastic process and failure occurs when the process first reaches a failure state or threshold (a first-hitting-time). Survival data with time-varying covariates consist of sequential observations on the level of degradation and/or on covariates of the subject, prior to the occurrence of the failure event. Encounters with this type of data structure abound in practical settings for survival analysis and there is a pressing need for simple regression methods to handle the longitudinal aspect of the data. Using a Markov property to decompose a longitudinal record into a series of single records is one strategy for dealing with this type of data. This study looks at the theoretical conditions for which this Markov approach is valid. The approach is called threshold regression with Markov decomposition or Markov TR for short. A number of important special cases, such as data with unevenly spaced time points and competing risks as stopping modes, are discussed. We show that a proportional hazards regression model with time-varying covariates is consistent with the Markov TR model. The Markov TR procedure is illustrated by a case application to a study of lung cancer risk. The procedure is also shown to be consistent with the use of an alternative time scale. Finally, we present the connection of the procedure to the concept of a collapsible survival model.

Bayesian modelling of lung cancer risk and bitumen fume exposure adjusted for unmeasured confounding by smoking

Objectives:Residual confounding can be present in epidemiological studies because information on confounding factors was not collected. A Bayesian framework, which has the advantage over frequentist methods that the uncertainty in...

CASE-CONTROL STUDY OF LUNG CANCER RISK FROM RESIDENTIAL RADON EXPOSURE IN WORCESTER COUNTY, MASSACHUSETTS

A study of lung cancer risk from residential radon exposure and its radioactive progeny was performed with 200 cases (58% male, 42% female) and 397 controls matched on age and sex, all from the same health maintenance organization. Emphasis was placed on accurate and extensive year-long dosimetry with etch-track detectors in conjunction with careful questioning about historic patterns of in-home mobility. Conditional logistic regression was used to model the outcome of cancer on radon exposure, while controlling for years of residency, smoking, education, income, and years of job exposure to known or potential carcinogens. Smoking was accounted for by nine categories: never smokers, four categories of current smokers, and four categories of former smokers. Radon exposure was divided into six categories (model 1) with break points at 25, 50, 75, 150, and 250 Bq m, the lowest being the reference. Surprisingly, the adjusted odds ratios (AORs) were, in order, 1.00, 0.53, 0.31, 0.47, 0.22, and 2.50 with the third category significantly below 1.0 (p < 0.05), and the second, fourth, and fifth categories approaching statistical significance (p < 0.1). An alternate analysis (model 2) using natural cubic splines allowed calculating AORs as a continuous function of radon exposure. That analysis produces AORs that are substantially less than 1.0 with borderline statistical significance (0.048 < or = p < or = 0.05) between approximately 85 and 123 Bq m. College-educated subjects in comparison to high-school dropouts have a significant reduction in cancer risk after controlling for smoking, years of residency, and job exposures with AOR = 0.30 (95% CI: 0.13, 0.69), p = 0.005 (model 1).

Measurement error in the explanatory variable of a binary regression: Regression calibration and integrated conditional likelihood in studies of residential radon and lung cancer

In epidemiology, one approach to investigating the dependence of disease risk on an explanatory variable in the presence of several confounding variables is by fitting a binary regression using a conditional likelihood, thus eliminating the nuisance parameters. When the explanatory variable is measured with error, the estimated regression coefficient is biased usually towards zero. Motivated by the need to correct for this bias in analyses that combine data from a number of case-control studies of lung cancer risk associated with exposure to residential radon, two approaches are investigated. Both employ the conditional distribution of the true explanatory variable given the measured one. The method of regression calibration uses the expected value of the true given measured variable as the covariate. The second approach integrates the conditional likelihood numerically by sampling from the distribution of the true given measured explanatory variable. The two approaches give very similar point estimates and confidence intervals not only for the motivating example but also for an artificial data set with known properties. These results and some further simulations that demonstrate correct coverage for the confidence intervals suggest that for studies of residential radon and lung cancer the regression calibration approach will perform very well, so that nothing more sophisticated is needed to correct for measurement error.

Inter-Rater Agreement for a Retrospective Exposure Assessment of Asbestos, Chromium, Nickel and Welding Fumes in a Study of Lung Cancer and Ionizing Radiation

A retrospective exposure assessment of asbestos, welding fumes, chromium and nickel (in welding fumes) was conducted at the Portsmouth Naval Shipyard for a nested case-control study of lung cancer risk from external ionizing radiation. These four contaminants were included because of their potential to confound or modify the effect of a lung cancer-radiation relationship. The exposure assessment included three experienced industrial hygienists from the shipyard who independently assessed exposures for 3519 shop/job/time period combinations. A consensus process was used to resolve estimates with large differences. Final exposure estimates were linked to employment histories of the 4388 study subjects to calculate their cumulative exposures. Inter-rater agreement analyses were performed on the original estimates to better understand the estimation process. Although concordance was good to excellent (78-99%) for intensity estimates and excellent (96-99%) for frequency estimates, overall simple kappa statistics indicated only slight agreement beyond chance (kappa < 0.2). Unbalanced distributions of exposure estimates partly contributed to the weak observed overall inter-rater agreement. Pairwise weighted kappa statistics revealed better agreement between two of the three panelists (kappa = 0.19-0.65). The final consensus estimates were similar to the estimates made by these same two panelists. Overall welding fume exposures were fairly stable across time at the shipyard while asbestos exposures were higher in the early years and fell in the mid-1970s. Mean cumulative exposure for all study subjects was 520 fiber-days cc(-1) for asbestos and 1000 mg-days m(-3) for welding fumes. Mean exposure was much lower for nickel (140 microg-days m(-3)) and chromium (45 microg-days m(-3)). Asbestos and welding fume exposure estimates were positively associated with lung cancer in the nested case-control study. The radiation-lung cancer relationship was attenuated by the inclusion of these two confounders. This exposure assessment provided exposure estimates that aided in understanding of the lung cancer-radiation relationship at the shipyard.

A Nested Case-Control Study of Lung Cancer Risk and Ionizing Radiation Exposure at the Portsmouth Naval Shipyard

Results have been inconsistent between studies of lung cancer risk and ionizing radiation exposures among workers at the Portsmouth Naval Shipyard (PNS). The purpose of this nested case-control study was to evaluate the relationship between lung cancer risk and external ionizing radiation exposure while adjusting for potential confounders that included gender, radiation monitoring status, smoking habit surrogates (socioeconomic status and birth cohort), welding fumes and asbestos. By incidence density sampling, we age-matched 3,291 controls selected from a cohort of 37,853 civilian workers employed at PNS between 1952 and 1992 with 1,097 lung cancer deaths from among the same cohort. Analyses using conditional logistic regression were conducted in various model forms: log-linear (main), linear excess relative risk (ERR), and categorical. Lung cancer risk was positively associated with occupational dose (OR = 1.02 at 10 mSv; 95% CI 0.99- 1.04) but flattened after the inclusion of work-related medical X-ray doses (OR = 1.00; 95% CI 0.98-1.03) in multivariate analyses. Similar risk estimates were observed in the linear ERR model at 10 mSv of cumulative exposure with a 15-year lag.

An Assessment of the Possible Extent of Confounding in Epidemiological Studies of Lung Cancer Risk Among Roofers

The U.S. roofing industry employs about 200,000 workers and estimates indicate about 50,000 on-roof workers are exposed to asphalt fumes during approximately 40% of their working hours. Numerous epidemiological studies have been conducted to evaluate cancer outcomes among roofers, including exposure to asphalt/bitumen fume. However, most studies relied on job title as a surrogate for exposure to asphalt or asphalt fumes because individual exposure data were not available. Therefore, it is unclear whether reported results of an increased risk of lung cancer reflect the direct impact of asphalt exposure on employee health, or if findings are due to bias, such as the presence of other risk factors for lung cancer (i.e., “confounding” exposures) or the use of comparison populations that are inherently different with respect to lung cancer risk. We evaluated the likelihood and extent to which the observed increased risk of lung cancer may be due to confounding (a mixing of effects of multiple exposures) by co-exposure to other potential carcinogens present in roofing or to lifestyle variables. We conducted a review of the epidemiological and industrial hygiene literature of asphalt-exposed workers. Peer-reviewed epidemiological studies of asphalt fumes, related occupational exposures, and confounding factors were identified from MEDLINE (1966– early 2004). Industrial hygiene studies of asphalt workers were identified through MEDLINE, publicly available government documents, and asphalt industry documents. Using well-established statistical methods, we quantified the extent to which lung cancer relative risk estimates among roofers reflect confounding from other exposures, using different prevalence and risk scenarios. The relative risk of lung cancer varied from 1.2 to 5.0 in 13 epidemiological studies of roofers; most studies reported a relative risk between 1.2 and 1.4. Smoking, asbestos and coal tar were the most likely confounders, but the prevalence of these factors varied over time. For example, smoking prevalence declined more steadily in the general population than among roofers, and coal tar and asbestos exposures among roofers have declined over the past 50 years. Depending on prevalence estimates used, the relative risk due to confounding ranged from 1.17 to 1.52 (current smoking); 1.36 to 1.78 (asbestos); and 1.04 to 2.32 (coal tar). The results of the study indicate that much of the observed risk reported in epidemiological studies of cancer among roofers is well within the range of what may have resulted from confounding by reasonable and expected levels of smoking, asbestos or coal tar. This may be particularly true for those studies that did not adjust for these confounders and where the exposure was defined as employment in the roofing industry. In addition to poorly defined asphalt exposure, uncontrolled confounding cannot reliably be ruled out in studies of lung cancer among asphalt-exposed roofers. Therefore, it is not possible to conclude whether roofers are at increased risk of lung cancer due to asphalt exposure. Future studies of roofers will require improved quantification of asphalt/bitumen exposure and confounding factors to provide more direct evidence regarding the specific role of occupational asphalt exposure in the etiology of lung cancer among roofers.

World Health Organization’s International Radon Project

Following initial in vitro and in vivo studies and important studies of uranium miners, scientists have now completed impressive case-control studies of lung cancer risk from exposure to residential radon. Researchers have pooled these studies, in which all the information from the individual studies was reanalyzed. These pooled analyzes confirm that in the context of residential exposure, radon is now an established risk factor for lung cancer. Many of the initial uncertainties have been reduced, and health risk assessors are now confident that radon may contribute to as much as 10% of the total burden of lung cancer—that is, 2% of all cancers in the population, worldwide. To reduce residential radon lung cancer risk, national authorities must have methods and tools based on solid scientific evidence and sound public health policies. To meet these needs, the World Health Organization (WHO) has initiated the WHO International Radon Project. This three year project, to be implemented during the period 2005–2008, will include (1) a worldwide database on national residential radon levels, radon action levels, regulations, research institutions, and authorities; (2) public health guidance for awareness-raising and mitigation; and (3) an estimation of the global burden of disease (GDB) associated with radon exposure.

Meta-analysis of case-referent studies of specific environmental or occupational pollutants on lung cancer

Meta-analysis is a statistical tool for combining and integrating the results of independent studies of a given scientific issue. The present investigation was initiated to investigate case-referent studies of lung cancer risk from specific environmental and occupational pollutants, using detailed individual exposure data. To examine the risk of lung cancer associated with environmental and occupational pollutants, a meta-analysis of published case-control studies was undertaken using a random effects model. For this study, the papers were selected for review from electronic search of PubMed, Medline and Google Scholar during 1990-2006. The principal outcome measure was the odds ratio for the risk of lung cancer. Twelve study reports detailing the relationship between the lung cancer and the type of exposure were identified. The odds ratio of asbestos, cooking fuel, cooking fumes, motor and diesel exhaust related to lung cancer were 1.67, 1.99, 2.52 and 1.42 (P < 0.001), respectively. The odds ratio of metal fumes related to lung cancer was 1.28 (0.001 P < 0.01). The combined odds ratio for the environmental and occupational exposure related to lung cancer was 1.67 (P < 0.001). The meta-analysis of the present study shows the magnitude association between asbestos, cooking fumes, cooking fuels, motor and diesel exhaust, with lung cancer risk. Lung cancer risk may be reduced by controlling exposure levels.

Exposition domestique au radon et risque de cancer du poumon : bilan des études cas-témoins

Radon is a radioactive gas that tends to accumulate in indoor environment. A causal relationship between lung cancer and radon exposure has been demonstrated in epidemiologic studies of miners. The objective of this paper is to present the results of case-control studies of lung cancer risk associated with indoor radon exposure. Case-control studies published since 1990 are included in this review. This type of protocol is particularly well suited for studying the relationship between indoor radon exposure and lung cancer risk, taking into account possible confounding factors such as tobacco smoking. The characteristics and results of these studies are summarized. The limitations associated with each of these studies are also discussed. The results of available studies are relatively concordant and suggest a positive association between lung cancer risk and indoor radon exposure with an estimated excess relative risk of about 6 to 9% per 100Bq/m3 increase in the observed time-weighted average radon concentration. The order of magnitude of this estimation agrees with extrapolations from miners but some studies may suffer from inadequate statistical power. At present, efforts are underway to pool together the data from the existing studies of indoor radon. This pooling analysis with thousands of cases and controls will provide a more precise estimate of the lung cancer risk from indoor radon exposure and explore the effect of modifying factors, such as smoking.

Czech studies of lung cancer risk from radon

Epidemiological evidence of lung cancer risk from radon is based mainly on studies of men employed underground in mines. One such study among uranium miners was established in 1970 by Josef Sevc. During the 1980s, another occupational study followed. In 1989, Sevc designed a new large cohort study among inhabitants exposed to high radon concentrations in homes. The paper reports recent results from extended follow-up of the two occupational cohorts and results from the residential study covering the period 1960–1999. A total of 915 and 216 cases of lung cancer were observed in the occupational and residential studies, respectively. These numbers not only allow evaluation of the risk from low and high exposures, but also the effect of temporal modifying factors and a comparison of the risk from occupational and residential exposure. Results of recent follow-up confirmed previous findings that excess relative risk from radon depends linearly on cumulative exposure experienced more than five years previously. In the occupational cohort, this relationship is strongly modified by time since exposure, age at exposure, and exposure rate. The effect from exposure more than 25 years ago was less than 7% of the risk related to exposure 5–14 years ago. Similar temporal patterns were observed in the residential cohort. The effect from unit exposure decreased to 29% after 20 years when compared to a period 5–19 years. In addition, the risk of lung cancer in the latter study is analysed using individual information on smoking habits. The estimate of the excess relative risk per standard unit concentration of radon gas (100 Bq/m³) is in line with findings from other residential studies. Adjustment for smoking did not change the estimate, however the risk among those who had never smoked was found higher by factor of nearly 2. In terms of detriment, the risk from concentrations of radon gas 1 kBq/m³ experienced 5–34 years previously in houses is approximately equal to the risk in mines with exposure rate 1 WLM/y and lasting for the same period.

Mechanistic modelling in large case-control studies of lung cancer risk from smoking.

The two-step clonal expansion (TSCE) model is applied to large case-control studies, frequency matched for age, which allow estimation of the RR of lung tumour risk caused by smoking. For estimating background hazard rates, mortality data from the study areas are used to supplement the case-control data. Two approaches are used to analyse the data, based on the unconditional and the conditional likelihoods. They are demonstrated to give nearly identical results. Some model diagnostics are performed and demonstrate a good model fit. Our results indicate that smoking acts on the promotion and transformation parameters, but not on the initiation parameter of the TSCE model. The fitted relative risk of current smokers peaks between ages 50 and 60 years. The relative risk of male ex-smokers decreases strongly with time since end of exposure, but does not reach the risk of non-smokers, and does not decrease as much as for female ex-smokers.

Czech miner studies of lung cancer risk from radon

Epidemiological evidence of lung cancer risk from radon is based mainly onstudies of miners. Two such studies among Czech uranium miners wereestablished in 1970 and 1980. A subcohort of 5002 miners and a nested-incase–control study contribute to a joint European project. In this paper, thesubcohort of miners with 495 lung cancers is described. The excess relativerisk depends linearly on cumulative exposure incurred more than 5 yearsbefore. The relative effect from exposures in the distant past decreases by62% per decade. Simultaneously, the excess relative risk is lower by 43%per decade in dependence on age at exposure. The effect of smoking,partly analysed in the study, suggests a twofold elevation in the relativerisk coefficient among non-smokers, but this difference is not significant.

Risk factors for lung cancer in Rio de Janeiro, Brazil: a case-control study

The association between the risk of lung cancer and tobacco smoking, dietary factors and occupational exposures was examined in a hospital-based case-control study. The study involved 123 consecutive cases and 123 controls, matched by age (± 3), sex, and race. In this first study of lung cancer risk in Brazil, we found that tobacco smoking is the strongest risk factor with an odds ratio (OR) for current and former smokers of 22 (C1, 6.5–76) and 7.7 (CI, 2.2–27), respectively. An OR of 2.8 (CI, 1.0–7.7) was found for users of black tobacco (in the form of hand-rolled cigarettes) in combination with conventional cigarettes, after adjustment for life-time consumption of any kind of tobacco; users of conventional cigarettes only were considered as a reference group. Cessation of smoking had an important influence in reducing the lung cancer risk, whereas early initiation of smoking increased the risk. Among dietary factors, frequent consumption of meat ( P < 0.01) and pasta ( P = 0.02) were positively associated with lung cancer risk after adjusting for smoking and income. No association was found with green/yellow vegetables or fruits. We were unable to detect any significant association related to occupational exposures. This study confirmed the association of lung cancer with smoking as the most important predictor of risk. It also indicates the increase in risk associated with the use of black tobacco in combination with conventional cigarettes.

Development and Use of a Welding Process Exposure Matrix in a Historical Prospective Study of Lung Cancer Risk in European Welders

A welding process exposure matrix has been developed relating 13 welding process-welded metal combinations to average exposure levels for total welding fumes, total chromium, chromium (VI) and nickel. Quantitative estimates were derived from consultation of literature sources and of some company data. This matrix was applied to the welding histories of 11,092 welders in the framework of an IARC multicentre study. When detailed welding history was not available at the individual level the average company welding practice profile was applied. No dose-response relationship emerged for lung cancer risk with cumulative dose of the carcinogens chromium (VI) and nickel for stainless steel welders. Dilution of the dose-response relationship could result from between-plant and within-plant variability, and exposure in jobs not accounted for in the study, but not from the partial use of company versus individual data. It is also possible that there is no increased risk related to chromium and nickel exposure in this group of workers. Matrix exposure estimates would need to be validated and the matrix possibly refined by comparison with a variety of comprehensive welding exposure data sets.