Non-genetic and genetic predictors of a superficial first basal cell carcinoma.

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.

Epidemiology of basal cell carcinoma: scholarly review.

Basal cell carcinoma (BCC) is the most common cancer in white-skinned individuals with increasing incidence rates worldwide. Patients with BCC place a large burden on healthcare systems, because of the high incidence and the increased risk of synchronous and metachronous BCCs and other ultraviolet radiation (UVR) related skin cancers (i.e. field cancerization). As a result, the disability-adjusted life years and healthcare costs have risen significantly in recent decades. BCC is a complex disease, in which the interplay between UVR, phenotype (UVR-sensitive) and genotype (somatic mutations and germline mutations/polymorphisms) fulfils a key role in the aetiopathogenesis. Prevention programmes with continual refinements and improvements could be of major importance in tackling the growing skin cancer problem. To provide the most appropriate BCC care, physicians should engage in shared decision-making and choose their treatments wisely.

Occurrence of metachronous basal cell carcinomas: a prognostic model.

BACKGROUND: A third of patients with a first basal cell carcinoma (BCC) will develop subsequent (metachronous) BCCs. OBJECTIVES: To study the prognostic effect of the number of previous BCC diagnosis dates a patient has experienced to derive a prediction model to assess the risk of metachronous BCCs that may inform individualized decision making on surveillance. METHODS: We considered participants of north-western European ancestry from a prospective population-based cohort study (Rotterdam Study). After linkage with the Dutch Pathology Registry, 1077 patients with a first BCC were included. Candidate predictors for metachronous BCCs included patient, lifestyle and tumour characteristics. The prognostic model was developed with Fine and Gray regression analysis to account for competing risk of death. We used bootstrapping to correct for within-patient correlation and statistical optimism in predictive performance. RESULTS: Second to fifth BCCs occurred in 293, 122, 58 and 36 patients, with median follow-up times of 3·0, 2·1, 1·7 and 1·8 years after the previous BCC, respectively. The risk of a new BCC was higher for patients with more metachronous BCCs. Having more than one BCC at diagnosis was another strong predictor of metachronous BCCs. Discriminative ability of the model was reasonable with an optimism-corrected c-index of 0·70 at 3 years. CONCLUSIONS: The number of previous BCC diagnosis dates was a strong prognostic factor and should be considered when predicting the risk of metachronous BCCs. When the number of previous BCC diagnosis dates is combined with other readily available characteristics into a prognostic model, patients at high risk of a new BCC can be identified.

Atopic dermatitis is not associated with actinic keratosis: cross-sectional results from the Rotterdam study.

BACKGROUND: Epidermal barrier impairment and an altered immune system in atopic dermatitis (AD) may predispose to ultraviolet-induced DNA damage. OBJECTIVES: To study the association between AD and actinic keratosis (AK) in a population-based cross-sectional study. METHODS: AD was defined by modified criteria of the U.K. working party's diagnostic criteria. AKs were diagnosed by physicians during a full-body skin examination, and keratinocyte cancers were identified via linkage to the national pathology database. The results were analysed in adjusted multivariable and multinomial models. RESULTS: A lower proportion of subjects with AD had AKs than those without AD: 16% vs. 24%, P = 0·002; unadjusted odds ratio (OR) 0·60, 95% confidence interval (CI) 0·42-0·83; adjusted OR 0·74, 95% CI 0·51-1·05; fully adjusted OR 0·69, 95% CI 0·47-1·07. In a multinomial model patients with AD were less likely to have ≥ 10 AKs (adjusted OR 0·28, 95% CI 0·09-0·90). No effect of AD on basal cell carcinoma or squamous cell carcinoma was found: adjusted OR 0·71, 95% CI 0·41-1·24 and adjusted OR 1·54, 95% CI 0·66-3·62, respectively. CONCLUSIONS: AD in community-dwelling patients is not associated with AK.