Lily Wang1, Rachel Bierbrier2, Aaron M Drucker3,4, An-Wen Chan3,4. 1. MD Program, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. 2. Division of Dermatology, McGill University Health Centre, Montreal, Quebec, Canada. 3. Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 4. Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada.
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.
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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