Asthma and lung cancer risk: a systematic investigation by the International Lung Cancer Consortium

Abstract

Asthma has been hypothesized to be associated with lung cancer (LC) risk. We conducted a pooled analysis of 16 studies in the International Lung Cancer Consortium (ILCCO) to quantitatively assess this association and compared the results with 36 previously published studies. In total, information from 585 444 individuals was used. Study-specific measures were combined using random effects models. A meta-regression and subgroup meta-analyses were performed to identify sources of heterogeneity. The overall LC relative risk (RR) associated with asthma was 1.28 [95% confidence intervals (CIs) = 1.16-1.41] but with large heterogeneity (I(2) = 73%, P < 0.001) between studies. Among ILCCO studies, an increased risk was found for squamous cell (RR = 1.69, 95%, CI = 1.26-2.26) and for small-cell carcinoma (RR = 1.71, 95% CI = 0.99-2.95) but was weaker for adenocarcinoma (RR = 1.09, 95% CI = 0.88-1.36). The increased LC risk was strongest in the 2 years after asthma diagnosis (RR = 2.13, 95% CI = 1.09-4.17) but subjects diagnosed with asthma over 10 years prior had no or little increased LC risk (RR = 1.10, 95% CI = 0.94-1.30). Because the increased incidence of LC was chiefly observed in small cell and squamous cell lung carcinomas, primarily within 2 years of asthma diagnosis and because the association was weak among never smokers, we conclude that the association may not reflect a causal effect of asthma on the risk of LC.

Fig. 1.

Forest plot of the association between asthma and LC risk: ILCCO studies. Pooled, pooled RR according a random effects model; heterogeneity I², percentage of inter-study heterogeneity; pooling all studies: the following eight studies were removed to reduce heterogeneity: HMGU.

Fig. 3.

Forest plot of the association between asthma and LC risk: published studies. Gender-specific RRs were included if no overall results are available, indicated as (m), male, and (f), female. Pooled, pooled RR according a random effects model; heterogeneity I², percentage of inter-study heterogeneity; pooling all studies: the following eight studies were removed to reduce heterogeneity: Vesterinen (19) (f), Osann (22), Brenner (56), Koshiol (60) (m), Boffetta (64), Ji (65), Turner (73), HMGU.

Fig. 2.

Subgroup meta-analysis. For some of the published studies, results from disjunctive subgroups (e.g. men and women) are reported. If so, subgroup estimates were used instead of overall results. For this reason, the number of subgroup results included need not to sum up to total number of selected studies. For published studies, asthma latency is defined as the minimal allowed latency by the design of a case–control study. Within the ILCCO pooled analysis, asthma latency was calculated for each study participant. Age, age at LC diagnosis (cases) or interview (controls); latency: asterisk indicates latency of 0–2 years; smoking: non-smokers, never- + former smokers + non-smokers (if so specified); ever smokers, former + current smokers + ever smokers (if so specified); heavy smokers, as defined in the original publication; histology: sqCLC, squamous cell carcinoma; non-SCLC, all types of LC apart from SCLC; LCLC, large cell lung carcinoma.

Fig. 4.

Forest plot of the association between asthma and LC risk: decade of study completion. Decade of study completion, RR estimate from the meta-regression for a study completed within the specified decade and of the ‘reference design’ defined as a case–control study with controls from a European Caucasian population of both sexes with mean age of 57 years, any type of smoking. Asthma should be assessed as self-reported diagnosis 3–10 years before the manifestation of LC. The analysis of such a ‘reference study’ was considered as adjusted for smoking but not for other lung diseases. Asterisk indicates excluded to reduce between-study heterogeneity; Double asterisk indicates 95% CI reconstructed; pooled, pooled RR according a random effects model; heterogeneity I², percentage of inter-study heterogeneity; pooling all studies: the following eight studies were removed to reduce heterogeneity: Vesterinen (19) (f), Osann (22), Brenner (56), Koshiol (60) (m), Boffetta (64), Ji (65), Turner (73), HMGU.