Abstract
Background: Several observational studies have suggested differences in the risk factor profile between patients with superficial basal cell carcinomas (BCCs) and non-superficial BCCs. Objective: To test the reproducibility of previous study findings and to find new genetic and non-genetic predictors for patients with a superficial first BCC. Methods: A total of 14.628 participants of northwestern European descent aged 45 years or older from a prospective population-based cohort study (Rotterdam Study) were linked with the Dutch Pathology Registry (PALGA) of whom 1528 were identified as BCC patients. After exclusion, 948 eligible BCC patients remained for further non-genetic analyses and 1014 for genetic analyses. We included 11 phenotypic, environmental and tumour-specific characteristics, and 20 candidate single nucleotide polymorphisms (SNP) as potential predictors for patients with a superficial first BCC. We performed binary logistic multivariable regression analyses. Results: We found that patients with a superficial first BCC were significantly younger, almost two times more often female and 12–18 times more likely to have their BCC on the trunk or extremities than patients with a non-superficial first BCC. One SNP (rs12203592), mapped to IRF4, looked promising (OR 1.83, 95% CI 1.13–2.97, P-value <0.05), but after adjustment for multiple testing, no significant differences in genetic make-up between superficial BCC and non-superficial BCC patients were found. Conclusion: We conclude that patients with a superficial BCC differ from non-superficial BCC patients with respect to environmental factors (tumour localization as a proxy for UVR exposure) and phenotypic characteristics (age and sex), but we found no difference in genotype. As superficial BCC patients develop their first BCCs at a younger age, they could be at higher lifetime risk for subsequent skin cancers and therefore be an important group for secondary prevention.
| Original language | English |
|---|---|
| Pages (from-to) | 533-540 |
| Number of pages | 8 |
| Journal | Journal of the European Academy of Dermatology and Venereology |
| Volume | 33 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2019 |
Bibliographical note
Funding Information:Funding source This study was supported by a Netherlands Organization for the Health Research and Development (ZonMw) (no. 91711315). The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The generation and management of GWAS genotype data for the Rotterdam Study (RS I, RS II, RS III) were executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. The GWAS datasets are supported by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012), the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA), project nr. 050-060-810. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera and Marjolein Peters, MSc, and Carolina Medina-Gomez, MSc, for their help in creating the GWAS database, and Karol Estrada, PhD, Yurii Aulchenko, PhD, and Carolina Medina-Gomez, MSc, for the creation and analysis of imputed data. We further thank Esther van den Broek and Lucy Overbeek from foundation PALGA, the Dutch Pathology Registry, for their help with the linkage. We also thank Senada Koljenovic for her help in the dermatopathology part of the linkage.
Funding Information:
This study was supported by a Netherlands Organization for the Health Research and Development (ZonMw) (no. 91711315).
Funding Information:
The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The generation and management of GWAS genotype data for the Rotterdam Study (RS I, RS II, RS III) were executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. The GWAS datasets are supported by the Netherlands Organisation of Scientific Research NWO Investments (nr.
Publisher Copyright:
© 2018 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.
