Original ResearchRisk factors for keratinocyte skin cancer in patients diagnosed with melanoma, a large retrospective study
Introduction
Although malignant melanoma remains the major cause of death associated with skin cancers, public awareness, early detection and improved treatment strategies have markedly prolonged patient survival. Increased incidence and improved survival have led to an ever increasing number of melanoma survivors. However, like survivors of other cancers, patients who survive melanoma are also at an increased risk of developing second primary malignancies, which include second melanomas and keratinocyte skin cancers (KSCs) [1], [2], [3], [4].
Considering the morbidity caused by KSC in melanoma survivors and the added burden to healthcare systems, it is important to identify factors associated with increased risk for such malignancies for targeted prevention efforts. We hypothesised that risk factors associated with both primary melanoma and KSC also increase KSC risk in melanoma survivors. Factors associated with both risk of melanoma and risk of KSC include susceptible skin phototype with propensity to sunburn and sun exposure. Genetic variations in low-penetrant pigmentation genes that are major determinants of predisposing phenotypes like skin and hair colour are also known risk factors for both melanoma and KSC [5], [6]. Variants in the melanocortin 1 receptor (MC1R) gene are among the most important genetic determinants of high-risk phenotypes like fair skin and red hair and consequently increased risk of skin cancers in general [7], [8], [9], [10], [11], [12], [13], [14], [15].
Despite known risk of KSC in patients who survived melanoma, no prospective study to date has assessed risk factors in detail. Thus, we investigated the association of personal, clinical and genetic factors with risk of developing of KSC in melanoma patients in a cohort of 1200 melanoma patients followed for over 10 years. We also estimated cumulative incidence of KSC risk to stratify patients for increased surveillance and preventative measures.
Section snippets
Patients and methods
Patients with cutaneous melanoma in this study include individuals who had been treated at the Instituto Valenciano de Oncología between 1st January 2000 and 31th December 2011. At the end of this period, the database contained information for 1792 incident and prevalent patients. A wide range of clinical, epidemiological and histological variables evaluated by dermatologists with specialised training in melanoma management were collected, as described in detail previously [16].
In brief, all
Results
The investigated population included 1200 patients with median age at diagnosis of the first primary melanoma of 56.8 years (range 18.4–96.1 years). The characteristics of the population are detailed in Table 1 and Supplementary Table 1 (by groups defined by the development of KSC, SCC or BCC). A 50.7% of the patients were female. Most patients (61.2%) had skin phototype III–V, dark hair (73.0%) and dark eyes (59.4%); 14.0% of patients reported intense sun exposure at work (for >20 years) and
Discussion
It is well known that patients with melanoma are at an elevated risk of developing non-melanoma skin cancers;[22] however, associated factors have not been comprehensively investigated. We thus studied cumulative incidence of KSC and related risk factors in a large cohort of melanoma patients. We also estimated the role of MC1R variants in the development of KSC, particularly BCC, in patients diagnosed with cutaneous melanoma. In our population, the estimated cumulative incidence of KSC in
Conflict of interest statement
None exists.
Authors' contribution to this study
Pablo Espinosa: literature search, data collection, and writing. Ruth M. Pfeiffer: study design, figures, data analysis, data interpretation, and writing. Zaida García-Casado: data collection and writing. Celia Requena: data collection. Maria Teresa Landi: data interpretation and critical revision of the manuscript. Rajiv Kumar: data collection, data interpretation, and writing. Eduardo Nagore: literature search, conception and design of the study, data collection, data interpretation, and
Acknowledgement
We thank Orestis Panagiotou for helpful comments.
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These authors contributed equally to this work.