Case-control Study Of Lung Cancer Research Articles

Abstract 2156: Childhood exposure to secondhand smoke, nicotine dependence, and DRD1 are associated with lung cancer risk

Abstract Children who are exposed to secondhand smoke (SHS) are faced with an increased risk of nicotine dependence later in life. We have previously shown that children exposed to SHS have an increased risk of lung cancer as adults. Furthermore, genetic variation plays a role in the susceptibility of individuals to lung cancer. The gene DRD1 mediates dopamine signaling following nicotine exposure, thus we reasoned that DRD1 may be related to lung cancer via modulation of the nicotine reward pathway. Our previous studies identified 4 SNPs (rs4809294, rs2292975, rs4861327, rs686) that were predicted to modulate a microRNA binding site and we assessed the association of these SNPs with lung cancer risk. Our current study investigated whether these SNPs were associated with nicotine dependence and whether this had a subsequent effect on lung cancer risk. We used the National Cancer Institute-Maryland lung cancer case-control study. Cases and controls were recruited from the greater Baltimore metropolitan area. We used ordinal logistic regression to examine the association between SNPs and nicotine dependence. Logistic regression adjusted for age, gender and smoking was used to assess the association between SNPs and lung cancer risk. No significant associations were found between genotypes in the 4 SNPs and nicotine dependence levels (n=1,450). Individuals with the heterozygous allele (AG) exposed to SHS during childhood had increased odds of lung cancer compared to those with the homozygous wild type allele (AA) for rs686 (OR=1.52, CI= 1.12, 2.07). Individuals with the homozygous variant allele (GG) exposed to childhood SHS had increased odds of lung cancer compared to individuals with the homozygous wild type allele (AA) (OR=2.11, CI= 1.45, 3.10). Individuals with the heterozygous allele (GA) and the highest levels of nicotine dependence who were also exposed to childhood SHS, had higher odds of lung cancer than those with the homozygous recessive allele (AA) (OR=3.50, CI=1.37, 8.96). Consistent with earlier findings, heterozygotes (AG) had increased odds of lung cancer but this was not statistically significant (OR=1.90, CI= 0.82, 4.40). To further explore this association, we examined the effect of race on this relationship. Caucasians with the heterozygous allele (AG), the highest levels of nicotine dependence and childhood SHS, had increased odds of lung cancer compared to those with the homozygous recessive allele (AA) for rs686 (OR=1.47, CI=1.06, 2.05). Caucasians with the homozygous allele (GG) who were exposed to childhood SHS, had higher odds of lung cancer compared to individuals with the homozygous recessive allele (AA) for rs686 (OR=1.84, CI=1.15, 2.98). No association was found among African Americans. Although none of the SNPs examined were found to be associated with nicotine dependence, it appears that variations in rs686 may modify an individual's susceptibility to lung cancer due to SHS exposure. Citation Format: Victoria A. Zigmont, Brid M. Ryan, Jin Jen, Ana I. Robles, Cain McClary, Kara Calhoun, Elise D. Bowman, Kirsi Vähäkangas, K. Leigh Greathouse, Wang Yi, Angela S. Wenzlaff, Bo Deng, Ping Yang, Ann G. Schwartz, Curtis C. Harris, Susan Olivo Marston. Childhood exposure to secondhand smoke, nicotine dependence, and DRD1 are associated with lung cancer risk. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2156. doi:10.1158/1538-7445.AM2014-2156

Re-contacting participants for inclusion in the database of Genotypes and Phenotypes (dbGaP): Findings from three case-control studies of lung cancer.

BackgroundSince January 2008, the National Institutes of Health (NIH) has required that all investigators who receive NIH support submit de-identified high-throughput genomic data to the database of Genotypes and Phenotypes (dbGaP). The purpose of this study was to explore the feasibility of re-consenting participants from three inactive studies, conducted from 2000 through 2009, to submit their data to dbGaP.MethodsParticipants were those enrolled in one of three prior population-based case-control studies of lung cancer who had given a DNA sample. Consent to release de-identified data to dbGaP took place via mailed forms and follow-up phone calls. Chi-squared tests were used to examine differences in re-contact and consent proportions between groups.ResultsA total of 2,471 participants were initially eligible for re-contact. Six hundred and thirty-eight participants were found to be deceased (n = 627) or did not give permission to re-contact (n = 11). Of the 1,833 remaining participants, 42.3% provided written consent, 37.0% could not be located, 13.7% verbally agreed to have their data released but never returned written consent, 5.3% refused, and 1.6% were too ill at the time of contact. There were significant differences in ability to locate participants by age, race, gender, and case-control status; however, once located, there were no differences in re-consent rates.ConclusionThis study demonstrates that while most previous study participants agreed to release data, a small proportion are opposed to submitting their data to dbGaP. In addition, it demonstrates the difficulty studies based on existing samples may have in locating inactive participants for re-consent.

Prevalence of COPD in a lung cancer case-control study: Variability by assessment method and by race.

1609 Background: The association between lung cancer risk and a history of self reported COPD (Chronic Obstructive Pulmonary Disease) is well established, but the association is less consistent whe...

Telomere length in peripheral blood leukocytes and lung cancer risk: a large case-control study in Caucasians.

Telomere dysfunction is a crucial event in malignant transformation and tumorigenesis. Telomere length in peripheral blood leukocytes has been associated with lung cancer risk, but the relationship has remained controversial. In this study, we investigated whether the association might be confounded by study of different histological subtypes of lung cancer. We measured relative telomere lengths in patients in a large case-control study of lung cancer and performed stratified analyses according to the two major histologic subtypes [adenocarcinoma and squamous cell carcinoma (SCC)]. Notably, patients with adenocarcinoma had longer telomeres than controls, whereas patients with SCC had shorter telomeres compared with controls. Long telomeres were associated with increased risk of adenocarcinoma, with the highest risk associated with female sex, younger age (<60 years), and lighter smoking (<30 pack-years). In contrast, long telomeres were protective against SCC, particularly in male patients. Our results extend the concept that telomere length affects risk of lung cancer in a manner that differs with histologic subtype.

A comparison of exposure assessment approaches: lung cancer and occupational asbestos exposure in a population-based case–control study

ObjectivesIn attempts to overcome the limitations of self-reported data in occupational health research, job-exposure matrices, which assign exposure by occupation, have emerged as an objective approach for assessing occupational exposures....

Comparison of exposure assessment methods in a lung cancer case-control study: performance of a lifelong task-based questionnaire for asbestos and PAHs

ObjectiveTo describe the performance of a lifelong task-based questionnaire (TBQ) in estimating exposures compared with other approaches in the context of a case-control study.MethodsA sample of 93 subjects was randomly...

57 An international historical cohort study of workers in the hard-metal industry

ObjectivesIn 2006, IARC found limited evidence in humans and sufficient evidence in animals that tungsten carbide (WC) with cobalt binder (WCCo) acted as a lung carcinogen (Group 2A). Our historical...

357 The two-phase design makes efficient use of expert-time in assessing exposure to occupational carcinogens: a lung cancer case-control study

ObjectivesTo identify dose-response relationship between lung cancer incidence and cumulative exposure to the main occupational carcinogens as assessed by experts making use of an initial algorithmic exposure assessment within the...

Neighbourhood socioeconomic status and individual lung cancer risk: Evaluating long-term exposure measures and mediating mechanisms

Neighbourhood socioeconomic status (SES) has been associated with numerous chronic diseases, yet little information exists on its association with lung cancer incidence. This outcome presents two key empirical challenges: a long latency period that requires study participants' residential histories and long-term neighbourhood characteristics; and adequate data on many risk factors to test hypothesized mediating pathways between neighbourhood SES and lung cancer incidence. Analysing data on urban participants of a large Canadian population-based lung cancer case-control study, we investigate three issues pertaining to these challenges. First, we examine whether there is an association between long-term neighbourhood SES, derived from 20 years of residential histories and five national censuses, and lung cancer incidence. Second, we determine how this long-term neighbourhood SES association changes when using neighbourhood SES measures based on different latency periods or at time of study entry. Third, we estimate the extent to which long-term neighbourhood SES is mediated by a range of individual-level smoking behaviours, other health behaviours, and environmental and occupational exposures. Results of hierarchical logistic regression models indicate significantly higher odds of lung cancer cases residing in the most compared to the least deprived quintile of the long-term neighbourhood SES index (OR: 1.46; 95% CI: 1.13–1.89) after adjustment for individual SES. This association remained significant (OR: 1.38; 1.01–1.88) after adjusting for smoking behaviour and other known and suspected lung cancer risk factors. Important differences were observed between long-term and study entry neighbourhood SES measures, with the latter attenuating effect estimates by over 50 percent. Smoking behaviour was the strongest partial mediating pathway of the long-term neighbourhood SES effect. This research is the first to examine the effects of long-term neighbourhood SES on lung cancer risk and more research is needed to further identify specific, modifiable pathways by which neighbourhood context may influence lung cancer risk.

Socioeconomic Status and Lung Cancer: Unraveling the Contribution of Genetic Admixture

We examined the relationship between genetic ancestry, socioeconomic status (SES), and lung cancer among African Americans and Latinos. We evaluated SES and genetic ancestry in a Northern California lung cancer case-control study (1998-2003) of African Americans and Latinos. Lung cancer case and control participants were frequency matched on age, gender, and race/ethnicity. We assessed case-control differences in individual admixture proportions using the 2-sample t test and analysis of covariance. Logistic regression models examined associations among genetic ancestry, socioeconomic characteristics, and lung cancer. Decreased Amerindian ancestry was associated with higher education among Latino control participants and greater African ancestry was associated with decreased education among African lung cancer case participants. Education was associated with lung cancer among both Latinos and African Americans, independent of smoking, ancestry, age, and gender. Genetic ancestry was not associated with lung cancer among African Americans. Findings suggest that socioeconomic factors may have a greater impact than genetic ancestry on lung cancer among African Americans. The genetic heterogeneity and recent dynamic migration and acculturation of Latinos complicate recruitment; thus, epidemiological analyses and findings should be interpreted cautiously.

Abstract 1502: Urinary biomarkers of polycyclic aromatic hydrocarbon and volatile organic carcinogens in relation to lung cancer development in lifelong never smokers - The Shanghai Cohort Study.

Abstract Background: In the United States, 10-15% of lung cancer victims are lifelong never smokers. Non-smoking related lung cancer alone ranks as the 6th most frequently diagnosed cancer. The etiological factors for non-smoking lung cancer are unclear. Although strong evidence supports a major role for polycyclic aromatic hydrocarbon (PAH) as causes of lung cancer in smokers, epidemiological studies prospectively investigating biomarkers of PAH and volatile organic carcinogens in relation to lung cancer risk among never smokers are lacking. Methods: A nested case-control study of lung cancer among never smokers was conducted within the Shanghai Cohort Study, a prospective cohort of 18,244 Chinese men aged 45-64 years at enrollment during 1986-1989. After more than 20 years of follow-up, we identified 96 incident lung cancer cases among never smokers. For each case, we randomly chose one control among cohort participants who were never smokers. The control was matched to the index case by age (±2 years), date of urine collection (±1 month) and neighborhood of residence. We quantified urinary free cotinine, 3-hydroxyphenanthrene (3-OH-Phe), total hydroxyphenanthrenes (the sum of 1-, 2-, 3-, and 4-OH-Phe) (total OH-Phe), r-1,t-2,3,c-4-tetrahdroxy-1,2,3,4-tetrahydrophenanthrene (PheT), mercapturic acid metabolites of acrolein [3-hydroxypropyl mercapturic acid (HPMA)], benzene [S-phenyl mercapturic acid (SPMA)], crotonaldehyde [4-hydroxybut-2-yl mercapturic acid (HBMA)], and ethylene oxide [2-hydroxyethyl mercapturic acid (HEMA)]. Self-reported never smokers whose urinary free cotinine was greater than 20 ng/ml were excluded from the present analysis for their potential use of tobacco. The odds ratio (OR) and 95% confidence interval (CI) for lung cancer for each urinary biomarker was estimated using an unconditional logistic regression method. Results: Among never smokers, urinary levels of all 3 measured PAH biomarkers were statistically significantly higher in cases than controls. The geometric means (pmol/mg creatinine) of total OH-Phe, 3-OH-Phe and PheT were 19.10 (in cases) vs 16.08 (in controls) (P = 0.017); 6.64 vs 5.44 (P = 0.011); and 19.84 vs 16.10 (P = 0.035), respectively. Compared with the lowest quartile, ORs (95% CIs) for lung cancer for the highest quartile were 2.59 (1.01-6.65) for total OH-Phe, 3.10 (1.12-7.75) for 3-OH-Phe, and 2.98 (1.13-7.87) for PheT (all Ptrend &amp;lt;0.05). There was no statistically significant difference in urinary levels of HPMA, SPMA, HBMA and HEMA between cases and controls. Conclusion: This is the first prospective study that demonstrates a positive association between urinary biomarkers of PAH and lung cancer risk among never smokers. Given its ubiquitous presence in the environment, PAH could account for large proportion of non-smoking related lung cancer. 1 Citation Format: Jian-Min Yuan, Yu-Tang Gao, Sharon Murphy, Steven G. Carmella, Renwei Wang, Heather H. Nelson, Stephen S. Hecht. Urinary biomarkers of polycyclic aromatic hydrocarbon and volatile organic carcinogens in relation to lung cancer development in lifelong never smokers - The Shanghai Cohort Study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1502. doi:10.1158/1538-7445.AM2013-1502

Abstract 1345: Evidence for genetic mediation of lung cancer through hay fever.

Abstract Introduction: In the past decade, advances in genetics have led to the discovery of numerous lung cancer susceptibility variants. The majority of these variants have been found to influence lung cancer susceptibility via tobacco exposure or nicotine addiction; however, recently, researchers have observed lung cancer susceptibility variants that mediate through Chronic Obstructive Pulmonary Disease (COPD). Studies involving potential genetic factors related to other lung-related conditions, such as pneumonia and/or hay fever have been limited. The genetic variants related to underlying mechanism of hay fever on the development of lung cancer are interesting to pursue as hay fever has been showed to be protective against lung cancer. Methods: Cases included 1154 histological-confirmed Caucasian lung cases from MD Anderson Cancer Center in Houston, Texas, and controls included 1137 individuals recruited through the Kelsey-Seybold Clinics in Houston, Texas. These cases and controls were a subset of participants from a lung cancer case-control study conducted that has available Genome-wide association study (GWAS) data (317,498 SNPs). We first conducted an association analysis in PLINK to determine the association of each SNP with both lung cancer and hay fever and find SNPs that showed a joint significance for both hay fever and lung cancer in opposite directions (p-value &amp;lt; 0.05 for both). We then performed mediation analyses with the SNPs that showed significance for both hay fever and lung cancer. Finally, we inferred SNPs in regions that contained a collection of tag SNPs that mediate lung cancer risk through hay fever. Results: Two hundred and forty six SNPs were found to be statistically significant (p-value &amp;lt; 0.05) for both hay fever (protection) and lung cancer (risk), and 76 of these SNPs maintained their significance level after mediation analysis. SNP rs7159751 on chromosome 14 had the highest mediation effect of 19.83%. A collection of SNPs on the Neuregulin 3 gene (NRG3) that mediate lung cancer risk through hay fever was found on Chromosome 10 which has been shown to activate the JAK-STAT signal transduction pathway and stimulate lung epithelial cell proliferation. Conclusion: This is the first study to have investigated the mediation effects of hay fever on lung cancer risk. Our data supports the mediation role of certain SNPs in lung cancer through hay fever and points to specific transduction pathway. Future studies are needed to validate these results in external populations. Citation Format: Anthony D'Amelio, Chi H. Nguyen, Randa El-Zein, Margaret R. Spitz, Xifeng Wu, Carol J. Etzel. Evidence for genetic mediation of lung cancer through hay fever. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1345. doi:10.1158/1538-7445.AM2013-1345

Joint Analysis of Three European Nested Case-control Studies of Lung Cancer among Radon Exposed Miners

Analyses of lung cancer risk were carried out using restrictions to nested case-control data on uranium miners in the Czech Republic, France, and Germany. With the data restricted to cumulative exposures below 300 working-level-months (WLM) and adjustment for smoking status, the excess relative risk (ERR) per WLM was 0.0174 (95% CI: 0.009-0.035), compared to the estimate of 0.008 (95% CI: 0.004-0.014) using the unrestricted data. Analysis of both the restricted and unrestricted data showed that time since exposure windows had a major effect; the ERR/WLM was six times higher for more recent exposures (5-24 y) than for more distant exposures (25 y or more). Based on a linear model fitted to data on exposures <300 WLM, the ERR WLM of lung cancer at 30 y after exposure was estimated to be 0.021 (95% CI: 0.011-0.040), and the risks decreased by 47% per decade increase in time since exposure. The results from analyzing the joint effects of radon and smoking were consistent with a sub-multiplicative interaction; the ERR WLM was greater for non-smokers compared with current or ex-smokers, although there was no statistically significant variation in the ERR WLM by smoking status. The patterns of risk with radon exposure from the combined European nested case-control miner analysis were generally consistent with those based on the BEIR VI Exposure-Age-Concentration model. Based on conversions from WLM to time weighted averaged radon concentration (expressed per 100 Bq m), the results from this analysis of miner data were in agreement with those from the joint analysis of the European residential radon studies.

Does a more refined assessment of exposure to bitumen fume and confounders alter risk estimates from a nested case-control study of lung cancer among European asphalt workers?

ObjectiveTo investigate whether a refined assessment of exposure to bitumen fume among workers in the European asphalt industry within a nested case-control study resulted in a different interpretation pertaining to...

Use of the Cytokinesis-Blocked Micronucleus Assay to Detect Gender Differences and Genetic Instability in a Lung Cancer Case–Control Study

Although tobacco exposure is the predominant risk factor for lung cancer, other environmental agents are established lung carcinogens. Measuring the genotoxic effect of environmental exposures remains equivocal, as increases in morbidity and mortality may be attributed to coexposures such as smoking. We evaluated genetic instability and risk of lung cancer associated with exposure to environmental agents (e.g., exhaust) and smoking among 500 lung cancer cases and 500 controls using the cytokinesis-blocked micronucleus (CBMN) assay. Linear regression was applied to estimate the adjusted means of the CBMN endpoints (micronuclei and nucleoplasmic bridges). Logistic regression analyses were used to estimate lung cancer risk and to control for potential confounding by age, gender, and smoking. Cases showed significantly higher levels of micronuclei and nucleoplasmic bridges as compared with controls (mean ± SEM = 3.54 ± 0.04 vs. 1.81 ± 0.04 and mean ± SEM = 4.26 ± 0.03 vs. 0.99 ± 0.03, respectively; P < 0.001) with no differences among participants with or without reported environmental exposure. No differences were observed when stratified by smoking or environmental exposure among cases or controls. A difference in lung cancer risk was observed between nonexposed male and female heavy smokers, although it was not statistically significant (I(2) = 64.9%; P value for Q statistic = 0.09). Our study confirms that the CBMN assay is an accurate predictor of lung cancer and supports the premise that heavy smoking may have an effect on DNA repair capacity and in turn modulate the risk of lung cancer. Identifying factors that increase lung cancer risk may lead to more effective prevention measures.

Method for Evaluating Multiple Mediators: Mediating Effects of Smoking and COPD on the Association between the CHRNA5-A3 Variant and Lung Cancer Risk

A mediation model explores the direct and indirect effects between an independent variable and a dependent variable by including other variables (or mediators). Mediation analysis has recently been used to dissect the direct and indirect effects of genetic variants on complex diseases using case-control studies. However, bias could arise in the estimations of the genetic variant-mediator association because the presence or absence of the mediator in the study samples is not sampled following the principles of case-control study design. In this case, the mediation analysis using data from case-control studies might lead to biased estimates of coefficients and indirect effects. In this article, we investigated a multiple-mediation model involving a three-path mediating effect through two mediators using case-control study data. We propose an approach to correct bias in coefficients and provide accurate estimates of the specific indirect effects. Our approach can also be used when the original case-control study is frequency matched on one of the mediators. We employed bootstrapping to assess the significance of indirect effects. We conducted simulation studies to investigate the performance of the proposed approach, and showed that it provides more accurate estimates of the indirect effects as well as the percent mediated than standard regressions. We then applied this approach to study the mediating effects of both smoking and chronic obstructive pulmonary disease (COPD) on the association between the CHRNA5-A3 gene locus and lung cancer risk using data from a lung cancer case-control study. The results showed that the genetic variant influences lung cancer risk indirectly through all three different pathways. The percent of genetic association mediated was 18.3% through smoking alone, 30.2% through COPD alone, and 20.6% through the path including both smoking and COPD, and the total genetic variant-lung cancer association explained by the two mediators was 69.1%.

Self-Reported Prior Lung Diseases as Risk Factors for Non-small Cell Lung Cancer in Mexican Americans

This study was conducted to assess the association between prior history of respiratory disease and lung cancer among Mexican Americans using data from a multi-racial/ethnic lung cancer case-control study. Cases (n = 204) were patients with previously untreated lung cancer. Healthy control participants (n = 325) were recruited from a large physician group practice. Demographics, cigarette use, and history of respiratory disease were collected. Multivariable logistic regression models were used to estimate relative risk. Prior history of COPD (OR = 2.0; 95 % CI 1.2-3.3) and pneumonia (OR = 2.2; 95 % CI 1.3-3.6) were associated with an increased risk of lung cancer. These findings illustrate that prior COPD and pneumonia are associated with an increased risk of lung cancer among Mexican Americans. To our knowledge, this is one of largest case-control analyses assessing the role of respiratory disease and lung cancer risk specifically among Mexican-Americans.

Occupational exposure to diesel engine emissions and risk of lung cancer: evidence from two case–control studies in Montreal, Canada

ObjectiveTo examine the risk of lung cancer among men associated with exposure to diesel engine emissions incurred in a wide range of occupations and industries.Methodology2 population-based lung cancer case–control studies...

Hierarchical Regression for Multiple Comparisons in a Case-Control Study of Occupational Risks for Lung Cancer

BackgroundOccupational studies often involve multiple comparisons and therefore suffer from false positive findings. Semi-Bayes adjustment methods have sometimes been used to address this issue. Hierarchical regression is a more general approach, including Semi-Bayes adjustment as a special case, that aims at improving the validity of standard maximum-likelihood estimates in the presence of multiple comparisons by incorporating similarities between the exposures of interest in a second-stage model.Methodology/Principal FindingsWe re-analysed data from an occupational case-control study of lung cancer, applying hierarchical regression. In the second-stage model, we included the exposure to three known lung carcinogens (asbestos, chromium and silica) for each occupation, under the assumption that occupations entailing similar carcinogenic exposures are associated with similar risks of lung cancer. Hierarchical regression estimates had smaller confidence intervals than maximum-likelihood estimates. The shrinkage toward the null was stronger for extreme, less stable estimates (e.g., “specialised farmers”: maximum-likelihood OR: 3.44, 95%CI 0.90–13.17; hierarchical regression OR: 1.53, 95%CI 0.63–3.68). Unlike Semi-Bayes adjustment toward the global mean, hierarchical regression did not shrink all the ORs towards the null (e.g., “Metal smelting, converting and refining furnacemen”: maximum-likelihood OR: 1.07, Semi-Bayes OR: 1.06, hierarchical regression OR: 1.26).Conclusions/SignificanceHierarchical regression could be a valuable tool in occupational studies in which disease risk is estimated for a large amount of occupations when we have information available on the key carcinogenic exposures involved in each occupation. With the constant progress in exposure assessment methods in occupational settings and the availability of Job Exposure Matrices, it should become easier to apply this approach.

Abstract 5478: Indoor coal smoke exposure, tobacco use, and lung cancer risk in Xuanwei, China

Abstract Introduction: Lung cancer rates in Xuanwei County, Yunnan Province are among the highest in China. We have previously reported that indoor combustion of smoky coal for home heating and cooking was associated with increased risk of lung cancer and that this effect varies markedly by coal type. Further, improved stove ventilation is followed by reduction in lung cancer risk. We explored the joint relationship between tobacco use and coal use in Xuanwei men. Methods: We analyzed data from a population-based case-control study of lung cancer in Xuanwei. Cases were identified from four Xuanwei hospitals and controls were selected from the general population by probability sampling. Controls were matched one-to-one with cases on age. In total, 260 cases and 260 controls were analyzed in this study. Tobacco, coal, and solid fuel exposures were tabulated from questionnaires and reported in cigarette pack-years, duration of smoking, and average tons of coal used annually. Odds ratios and 95% confidence intervals were estimated by conditional logistic regression with the main effects of coal, smoking, and coal-smoking interaction terms. Results: Overall, smoking was positively and significantly, although only modestly, associated with lung cancer risk (OR per pack-year: 1.02; 95% CI: 1.01-1.04). The risk of lung cancer per pack-year of smoking decreased as cumulative lifetime use of smoky coal increased (0-50 tons coal: OR: 1.07; 95% CI: 1.01-1.15; &amp;gt;50-150 tons coal: OR: 1.05; 95% CI: 1.01-1.10; &amp;gt;150 tons coal: OR: 1.00; 95% CI: 0.99-1.03; P-interaction: 0.041). Discussion: Our results suggest that the effect of tobacco on lung cancer risk was weaker in men exposed to higher amounts of coal. Results are consistent with previous cohort study findings in Xuanwei. Constituents of coal combustion, such as polycyclic aromatic hydrocarbons, could plausibly act to diminish the carcinogenicity of tobacco through metabolic competition or other possible mechanisms. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5478. doi:1538-7445.AM2012-5478