European Journal of Epidemiology

, Volume 28, Issue 7, pp 557–567 | Cite as

Competing risk bias to explain the inverse relationship between smoking and malignant melanoma

  • Caroline A. ThompsonEmail author
  • Zuo-Feng Zhang
  • Onyebuchi A. Arah


The relationship between smoking and melanoma remains unclear. Among the different results is the paradoxical finding that smoking was shown to be inversely associated with the risk of malignant melanoma in some large cohort and case-control studies, even after control for suspected confounding variables. Smoking is a known risk factor for many non-communicable diseases, including coronary heart disease, stroke, as well as other malignancies; it has been shown to be positively associated with other types of skin cancer, and there remains no clear biologic explanation for a possible protective effect on malignant melanoma. In this paper, we propose a plausible mechanism of bias from smoking-related competing risks that may explain or contribute to the inverse association between smoking and melanoma as spurious. Using directed acyclic graphs for formalization and visualization of assumptions, and Monte Carlo simulation techniques, we demonstrate how published inverse associations might be compatible with selection bias resulting from uncontrolled or unmeasured common causes of competing outcomes of smoking-related diseases and malignant melanoma. We present results from various scenarios assuming a true null as well as a true positive association between smoking and malignant melanoma. Under a true null assumption, we find inverse associations due to the biasing mechanism to be compatible with published results in the literature, especially after the addition of unmeasured confounding variables. This study could be seen as offering a cautionary note in the interpretation of published smoking-melanoma findings.


Bias (Epidemiology) Melanoma Smoking 





Chronic obstructive pulmonary disease


Competing risk


Directed acyclic graph


Heart disease


Malignant melanoma


Odds ratio





This work was supported by the National Institutes of Health [grant number CA09142]. CAT was supported by a pre-doctoral fellowship from the National Institutes of Health, National Cancer Institute T32 CA09142. OAA was supported by a Veni career grant (# 916.96.059) from the Netherlands Organization for Scientific Research (NWO). Preliminary results from this study were presented in a spotlight session at the 3rd North American Congress of Epidemiology, in Montreal, Canada, in June 2011. The authors wish to thank Maral DerSarkissian for her comments on earlier drafts of this work.

Conflict of interest

The authors declare they have no conflict of interest.


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Caroline A. Thompson
    • 1
    Email author
  • Zuo-Feng Zhang
    • 1
    • 2
  • Onyebuchi A. Arah
    • 1
    • 3
    • 4
  1. 1.Department of EpidemiologyUCLA Fielding School of Public HealthLos AngelesUSA
  2. 2.UCLA Jonsson Comprehensive Cancer CenterLos AngelesUSA
  3. 3.UCLA Center for Health Policy ResearchLos AngelesUSA
  4. 4.Department of Public Health, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands

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