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Abstract
in English, Chinese, Chinese

Background: The high relapse and mortality rate of small-cell lung cancer (SCLC) fuels the need for epidemiologic study to aid in its prevention.

Methods: We included 24 studies from the ILCCO collaboration. Random-effects panel logistic regression and cubic spline regression were used to estimate the effects of smoking behaviors on SCLC risk and explore their non-linearity. Further, we explored whether the risk of smoking on SCLC was mediated through COPD.

Findings: Significant dose-response relationships of SCLC risk were observed for all quantitative smoking variables. Smoking pack-years were associated with a sharper increase of SCLC risk for pack-years ranged 0 to approximately 50. The former smokers with longer cessation showed a 43%quit_for_5-9 years to 89%quit_for_≥ 20 years declined SCLC risk vs. subjects who had quit smoking < 5 years. Compared with non-COPD subjects, smoking behaviors showed a significantly higher effect on SCLC risk among COPD subjects, and further, COPD patients showed a 1.86-fold higher risk of SCLC. Furthermore, smoking behaviors on SCLC risk were significantly mediated through COPD which accounted for 0.70% to 7.55% of total effects.

Interpretation: This is the largest pooling study that provides improved understanding of smoking on SCLC, and further demonstrates a causal pathway through COPD that warrants further experimental study.

Background: The high relapse and mortality rate of small-cell lung cancer (SCLC) fuels the need for epidemiologic study to aid in its prevention.

Methods: We included 24 studies from the ILCCO collaboration. Random-effects panel logistic regression and cubic spline regression were used to estimate the effects of smoking behaviors on SCLC risk and explore their non-linearity. Further, we explored whether the risk of smoking on SCLC was mediated through COPD.

Findings: Significant dose–response relationships of SCLC risk were observed for all quantitative smoking variables. Smoking pack-years were associated with a sharper increase of SCLC risk for pack-years ranged 0 to approximately 50. The former smokers with longer cessation showed a 43%quit_for_5–9 years to 89%quit_for_≥ 20 years declined SCLC risk vs. subjects who had quit smoking < 5 years. Compared with non-COPD subjects, smoking behaviors showed a significantly higher effect on SCLC risk among COPD subjects, and further, COPD patients showed a 1.86-fold higher risk of SCLC. Furthermore, smoking behaviors on SCLC risk were significantly mediated through COPD which accounted for 0.70% to 7.55% of total effects.

Interpretation: This is the largest pooling study that provides improved understanding of smoking on SCLC, and further demonstrates a causal pathway through COPD that warrants further experimental study.

•Cumulative smoking of the first 50 pack-years is associated with a sharper increase in SCLC risk.•Smoking behaviors have a higher risk on SCLC among COPD subjects, and COPD patients have a 1.86-fold higher risk of SCLC.•Risks of smoking behaviors on SCLC are partially mediated through COPD.A strong association between smoking and SCLC is noted whereas the dose–response relationships are less clear. We demonstrate that cumulative smoking of the first 50 pack-years is associated with a sharper increase in SCLC risk. Moreover, although the relationship between smoking and COPD or COPD and SCLC is well-established, no study has investigated the causal pathway among smoking, COPD, and SCLC. Here we reveal the risks of smoking behaviors on SCLC which are partially mediated (up to 7.6%) through COPD. The findings warrant further experimental study to elucidate the mechanisms in this causal pathway.

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Figures

Fig. 1
Fig. 1
The dose–response relationship between smoking behaviors and the risk of SCLC. Smoking pack-years were explored on the non-linear dose–response relationship on SCLC risk among all samples (a), or stratified by COPD status (b, c), by gender (d, e), or by study areas (f, g). Time since quitting smoking was also explored by cubic spline regressions for non-linearity among all samples (h), or stratified by COPD status (i, j), by gender (k, l), or among Caucasian-dominated areas (m). Due to insufficient sample size, there was no subgroup analysis done among non-Caucasian-dominated areas. The x-axis represents the quantitative smoking information while the y-axis represents the odds in loge scale.
Fig. 2
Fig. 2
A diagram of mediation model.
See this image and copyright information in PMC

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References

    1. Armstrong B.G., Sloan M. Ordinal regression models for epidemiologic data. Am. J. Epidemiol. 1989;129(1):191–204. - PubMed
    1. Ballaz S., Mulshine J.L. The potential contributions of chronic inflammation to lung carcinogenesis. Clin. Lung Cancer. 2003;5(1):46–62. - PubMed
    1. Barr R.G., Herbstman J., Speizer F.E., Camargo C.A., Jr. Validation of self-reported chronic obstructive pulmonary disease in a cohort study of nurses. Am. J. Epidemiol. 2002;155(10):965–971. - PubMed
    1. Bednarek M., Maciejewski J., Wozniak M., Kuca P., Zielinski J. Prevalence, severity and underdiagnosis of COPD in the primary care setting. Thorax. 2008;63(5):402–407. - PubMed
    1. Brenner D.R., Hung R.J., Tsao M.S. Lung cancer risk in never-smokers: a population-based case–control study of epidemiologic risk factors. BMC Cancer. 2010;10:285. - PMC - PubMed

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