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Original Investigation
December 11, 2019

Noncutaneous and Cutaneous Cancer Risk in Patients With Atopic Dermatitis: A Systematic Review and Meta-analysis

Author Affiliations
  • 1MD Program, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
  • 2Division of Dermatology, McGill University Health Centre, Montreal, Quebec, Canada
  • 3Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  • 4Women’s College Research Institute, Women’s College Hospital, Toronto, Ontario, Canada
JAMA Dermatol. 2020;156(2):158-171. doi:10.1001/jamadermatol.2019.3786
Key Points

Question  What is the risk of noncutaneous and cutaneous cancers in patients with atopic dermatitis (AD) compared with the general population?

Findings  This systematic review and meta-analysis included 8 population-based cohort studies (n = 5 726 692) and 48 case-control studies (n = 14 136). In population-based cohort studies, AD was statistically significantly associated with keratinocyte carcinoma (5 studies) and kidney cancer (2 studies), whereas case-control studies demonstrated lower odds of lung and respiratory system cancers (4 studies).

Meaning  Despite evidence suggesting potential associations between AD and the risk of some cancers, more research is needed to address heterogeneity and biases across existing studies to make definitive conclusions.

Abstract

Importance  Impaired skin barrier and aberrant immune function in atopic dermatitis (AD) may alter immune response to malignant cancer. Conflicting data exist on the risk of cancer in patients with AD.

Objective  To assess the risk of noncutaneous and cutaneous cancers in patients with AD compared with the general population without AD.

Data Sources  Studies identified from searches of MEDLINE and Embase that were published from 1946 and 1980, respectively, to January 3, 2019. The following search terms were used: [(exp NEOPLASMS/ OR neoplas*.tw. OR tumo*.tw. OR cancer*.tw. OR malignanc*.tw.) AND (exp Dermatitis, Atopic/ OR (atopic adj1 (dermatit* or neurodermatit*)).tw. OR eczema.tw. OR disseminated OR neurodermatit*.tw.)].

Study Selection  Included were observational studies (cohort and case-control designs) reporting a risk estimate for cancer in patients with AD compared with a control group (general population or patients without AD).

Data Extraction and Synthesis  Two independent reviewers extracted data and assessed the risk of bias using the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) assessment tool, modified for observational exposure studies. Data were pooled using a random-effects model and expressed as standardized incidence ratios (SIRs) or odds ratios (ORs) with 95% CIs. Heterogeneity was assessed using the Cochrane Q statistic and the I2 statistic.

Main Outcomes and Measures  The main outcome of the study was risk of cancer measured by SIRs or ORs.

Results  This systematic review and meta-analysis included 8 population-based cohort studies (n = 5 726 692 participants) and 48 case-control studies (n = 114 136 participants). Among cohort studies, a statistically significant association was found between AD and keratinocyte carcinoma (5 studies; pooled SIR, 1.46; 95% CI, 1.20-1.77) as well as cancers of the kidney (2 studies; pooled SIR, 1.86; 95% CI, 1.14-3.04), central nervous system (2 studies; pooled SIR, 1.81; 95% CI, 1.22-2.70), and pancreas (1 study; SIR, 1.90; 95% CI, 1.03-3.50). Among 48 case-control studies, pooled effects showed patients with AD had statistically significantly lower odds of central nervous system cancers (15 studies; pooled OR, 0.76; 95% CI, 0.70-0.82) and pancreatic cancer (5 studies; pooled OR, 0.81; 95% CI, 0.66-0.98), contrary to the higher incidence found in cohort studies. Case-control studies also demonstrated lower odds of lung and respiratory system cancers (4 studies; pooled OR, 0.61; 95% CI, 0.45-0.82). No evidence of association was found between AD and other cancer types, including melanoma. There was substantial heterogeneity between studies for many other cancers, which precluded pooling of data, and there was moderate to serious risk of bias among included studies.

Conclusions and Relevance  Observational evidence suggests potential associations between AD and increased risk of keratinocyte carcinoma and kidney cancer as well as lower odds of lung and respiratory system cancers. Further research is needed to address the heterogeneity and limitations of current evidence and to better understand the mechanisms underlying a possible association between AD and cancer risk.

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