Cigarette Smoking and the Risk of Cutaneous Melanoma: A Case-Control Study.

OBJECTIVE: Previous studies regarding cigarette smoking causing a lower risk of melanoma are inconclusive. Here, we re-examined melanoma risk in relation to cigarette smoking in a large, case-control study. METHODS: In total 1,157 patients with melanoma diagnosed between 2003 and 2011 in the Netherlands and 5,595 controls from the Nijmegen Biomedical Study were included. Information concerning smoking habits and known risk factors for melanoma were obtained through self-administered questionnaires. Logistic regression analyses stratified by gender were performed to study the risk of cigarette smoking on melanoma risk, adjusted for age, marital status, highest level of education, skin type, sun vacation, use of solarium, time spent outdoors, and sun protective measures. RESULTS: Among men, current and former smokers did not have a higher risk of melanoma compared to never smokers: adjusted odds ratio (OR) = 0.56 (95% confidence interval [CI]: 0.40-0.79) and adjusted OR = 0.50 (95% CI: 0.39-0.64), respectively. With an increasing number of years smoked the risk of melanoma decreased: <20 years: OR = 0.61 (95% CI: 0.46-0.80); 21-40 years: OR = 0.50 (95% CI: 0.37-0.68); >40 years: OR = 0.26 (95% CI: 0.15-0.44). No clear trend was found for the number of cigarettes smoked. Results for females were less clear and not statistically significant (current smoker: adjusted OR = 0.96, 95% CI: 0.74-1.26, former smoker: adjusted OR = 0.89, 95% CI: 0.73-1.08). CONCLUSION: This study shows a strong inverse association between cigarette smoking and melanoma risk in men. Fundamental laboratory research is necessary to investigate the biological relation between smoking cigarettes and melanoma.

Extensive segmental acanthosis nigricans form of epidermal nevus.

Eight cases of the acanthosis nigricans form of epidermal nevus have been described in literature. The present case is impressive and has an extensive segmental distribution. Although etiological factors, such as mutations in the FGFR3 gene, are becoming recognized, treatment options remain limited. We present a case of a 14-year-old male with multiple hyperpigmented, hyperkeratotic plaques on the upper body, axillae, and groin with a segmental distribution following Blaschko lines. Histopathological investigation showed aspects of both acanthosis nigricans and epidermal nevus. So far, screening has not revealed any internal abnormalities. As previous cases show a clear association with internal diseases, repetitive screening for internal diseases and syndromes is suggested in the case of the acanthosis nigricans form of epidermal nevus. Treatment of the condition remains a challenge.

Reproducibility of self-reported melanoma risk factors in melanoma patients.

As melanoma researchers continue to investigate environmental and lifestyle-related risk factors, questionnaire data remain important. The reproducibility of a questionnaire on melanoma risk factors was investigated using a test-retest approach in 389 Dutch melanoma patients. In 2011, 389 melanoma patients filled out a questionnaire on melanoma risk factors twice. Test-retest reproducibility was assessed by calculating kappas (κ), weighted kappas (κw), and intraclass correlation coefficients (ICCs) for categorical, ordinal, and continuous variables, respectively. Stratified analyses were carried out by sex, age group, education level, and time since diagnosis. The median time between the questionnaires was 31 days. The reproducibility was substantial for questions on phenotypic characteristics (κ/κw/ICC=0.62-0.77), fair-to-substantial for sun exposure and sun protection behavior (κ/κw/ICC=0.38-0.79), and moderate for sunburn history (κ/κw=0.42-0.51). No clear differences were observed between men and women. Younger patients showed a better reproducibility in nine of the 29 questions compared with older patients and higher educated patients showed a better reproducibility in four of the 29 questions. Patients with a diagnosis shorter than 1.5 years ago had a better reproducibility in four out of 29 items compared with patients with a diagnosis 1.5-3.0 years ago. Our study showed that self-reported information on melanoma risk factors is fairly well reproducible. Although this does not guarantee validity, this type of questionnaire seems to be useful in research settings. The reproducibility is slightly better in young patients and patients with a higher education level, which can be taken into account when interpreting results from epidemiological studies.

Melanoma of unknown primary origin: a population-based study in the Netherlands.

AIM: Few population-based studies have been published on melanoma of unknown primary origin (MUP). This study's aim is to describe characteristics and survival of MUP patients in the Netherlands, based on nationwide data from the Netherlands Cancer Registry (NCR). METHODS: Patient and tumour characteristics of MUP patients were retrieved from the NCR. Subgroups were made according to metastatic site: nodal or distant. Survival rates were calculated using the Kaplan-Meier method. To obtain a better insight in the composition and prognosis of the MUP group, the survival was compared to that of patients with melanoma of a known primary origin (MKP), tumour-node-metastasis (TNM) stage III and IV. RESULTS: Of all 33,181 melanoma patients diagnosed between 2003 and 2009, 2.6% (n=857) were diagnosed with MUP. MUP patients with nodal metastases had a similar survival as MKP stage III with macroscopic nodal involvement. After stratification according to the number of involved lymph nodes, the survival of patients with nodal metastases with one involved lymph node was not significantly different between MUP and MKP. The survival of MUP patients with two or more involved lymph nodes was slightly worse than that of MKP stage III patients with macroscopic nodal involvement with two or more involved lymph nodes. MUP patients with distant metastases had a similar survival as MKP stage IV. After stratification according to number of metastatic sites and metastatic site category, the survival in MKP stage IV patients with (sub)cutaneous metastases was slightly worse than MUP distant patients with (sub)cutaneous metastases. CONCLUSIONS: The results of this study imply that MUP patients form a heterogeneous group, and that MUP patients with nodal metastases could be classified as stage III melanoma with macroscopic nodal involvement, and MUP patients with distant metastases as stage IV melanoma.

A variant in FTO shows association with melanoma risk not due to BMI.

We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 × 10(-12), per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanoma-susceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTO's function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.

Pustulosis palmoplantaris is a disease distinct from psoriasis.

Pustulosis palmoplantaris (PPP) is a chronic inflammatory skin disease with a considerable impairment of quality of life and is characterized by sterile pustules and red, scaly skin on the palms and soles. The position of PPP in relation to psoriasis is unclear. Some authors regard PPP as a distinct disease entity, whereas others categorize PPP as a manifestation of psoriasis. Related to this discussion is the question on the treatment of PPP. Should the treatment of PPP follow the guidelines for psoriasis or is it a disease that has to be treated in a different way? The purpose of this editorial is to review the differences between PPP and psoriasis and to understand these differences with respect to the pathogenesis and treatment.