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Cancer Prevention Research
Cancer Prevention Research
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Research Article

Risk of Skin Cancer Associated with Metformin Use: A Meta-Analysis of Randomized Controlled Trials and Observational Studies

Michael S. Chang, Rebecca I. Hartman, Junchao Xue, Edward L. Giovannucci, Hongmei Nan and Keming Yang
Michael S. Chang
1Department of Dermatology, Brigham and Women's Hospital & Harvard Medical School, Boston, Massachusetts.
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Rebecca I. Hartman
1Department of Dermatology, Brigham and Women's Hospital & Harvard Medical School, Boston, Massachusetts.
2Department of Dermatology, VA Integrated Service Network (VISN-1), Jamaica Plain, Massachusetts.
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  • ORCID record for Rebecca I. Hartman
Junchao Xue
3Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana.
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Edward L. Giovannucci
4Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
5Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
6Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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Hongmei Nan
3Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana.
7Department of Global Health, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana.
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Keming Yang
4Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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  • For correspondence: kyang@hsph.harvard.edu
DOI: 10.1158/1940-6207.CAPR-20-0376 Published January 2021
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Abstract

Previous studies demonstrate mixed evidence regarding the association between metformin and skin cancer risk. To synthesize prior evidence and evaluate the association between metformin and skin cancer risk in patients with diabetes/prediabetes, we conducted a meta-analysis. A systematic literature search was performed up to March 23, 2020 to identify randomized controlled trials (RCT) and observational studies of metformin that reported any event of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma. In a meta-analysis of 6 trials involving 8,541 patients (Peto method), compared with controls, metformin was not significantly associated with decreased risk of melanoma [OR, 0.82; 95% confidence interval (CI), 0.27–2.43], BCC (OR, 0.75; 95% CI, 0.36–1.57), SCC (OR, 0.98; 95% CI, 0.06–15.60), total nonmelanoma skin cancer (NMSC; OR, 0.69; 95% CI, 0.38–1.24), or total skin cancer (OR, 0.71; 95% CI, 0.42–1.20). This nonsignificant association pattern was consistent with the random-effects meta-analysis of 4 cohort studies with 354,746 patients (melanoma: RR, 0.91; 95% CI, 0.62–1.33; NMSC: RR, 0.65; 95% CI, 0.35–1.18; total skin cancer: RR, 0.83; 95% CI, 0.59–1.16). In conclusion, meta-analyses of both RCT and cohort studies showed no statistically significant association between metformin and skin cancer risks, although suggestive evidence of modestly reduced risks of skin cancer among metformin users was observed. Further studies are needed.

Prevention Relevance: Meta-analyses of RCT and cohort studies showed no significant association between metformin and skin cancer, although suggestive evidence of modestly reduced skin cancer risks among metformin users was observed. These findings suggest metformin use should not influence current medical decision making for diabetes patients at risk of developing skin cancer.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Prevention Research Online (http://cancerprevres.aacrjournals.org/).

  • Cancer Prev Res 2021;14:77–84

  • Received July 14, 2020.
  • Revision received August 26, 2020.
  • Accepted September 15, 2020.
  • Published first September 21, 2020.
  • ©2020 American Association for Cancer Research.
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Cancer Prevention Research: 14 (1)
January 2021
Volume 14, Issue 1
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Risk of Skin Cancer Associated with Metformin Use: A Meta-Analysis of Randomized Controlled Trials and Observational Studies
Michael S. Chang, Rebecca I. Hartman, Junchao Xue, Edward L. Giovannucci, Hongmei Nan and Keming Yang
Cancer Prev Res January 1 2021 (14) (1) 77-84; DOI: 10.1158/1940-6207.CAPR-20-0376

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Risk of Skin Cancer Associated with Metformin Use: A Meta-Analysis of Randomized Controlled Trials and Observational Studies
Michael S. Chang, Rebecca I. Hartman, Junchao Xue, Edward L. Giovannucci, Hongmei Nan and Keming Yang
Cancer Prev Res January 1 2021 (14) (1) 77-84; DOI: 10.1158/1940-6207.CAPR-20-0376
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