The D84E variant of the alpha-MSH receptor 1 gene is associated with cutaneous malignant melanoma early onset.

BACKGROUND: Alpha-melanocyte-stimulating hormone receptor 1 (MC1R) has an important role in skin pigmentation and variants of the gene have been established as independent risk factors for susceptibility to cutaneous malignant melanoma. OBJECTIVE: To explore whether variants of the gene also influence the onset of the disease. METHODS: We analyzed 285 melanoma patients of European ancestry for common variation in codon 84 (D84E) of the alpha-MSH receptor 1 gene, which is known to have functional consequences in MC1R protein activity. RESULTS: The mean age difference at diagnosis between MC1R 84E carriers and non-carriers was 9 years (95% confidence interval [CI]: 2-17; p=0.012), with 84E non-carrier patients being older. After adjusting for gender, Clark's level, phototype, eyes and hair colour, the risk for cutaneous malignant melanoma at any age was 2.07 times higher (95% CI: 1.21-3.52; p=0.008) among MC1R 84E carriers. Enrolment criteria, geographical origin, Clark's levels and Breslow's indexes were similar between MC1R 84E carriers and non-carriers. Further analyses based on the Clark level and Breslow's index, both indicative for cancer invasion, reasonably supported an unbiased selection of patients during the study enrolment. Additional exon re-sequencing of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene in MC1R 84E carriers ruled out the presence of high penetrance mutations that have previously been associated with early onset of the disease. CONCLUSION: Although our findings need to be confirmed by independent and larger studies we have described for the first time the association of D84E variant of the alpha-MSH receptor 1 gene as an independent risk factor for an earlier onset of cutaneous malignant melanoma.

Clinicopathological characteristics of cutaneous malignant melanoma in patients at a tertiary hospital in Macaronesia. Survival as a function of locoregional prognostic factors per the American Joint Committee on Cancer.

BACKGROUND: Despite suffering high ultraviolet radiation levels, few data on malignant melanoma (MM) in Macaronesia are available. METHODS: Observational study of cutaneous MM cases diagnosed during a period of 12 years at a tertiary hospital in Canary Islands. RESULTS: A total of 532 patients (female/male = 1.4) with an average age of 56 years were included; 5% developed more than one MM, and 7% reported family history of MM. Phototype II (43%), dark eyes (41%), and dark hair (41%) predominated. There was a lower frequency of light-colored hair and eyes in those born in the Canary Islands. The most frequent locations of MM were on the back for men (37%) and on the lower extremities for women (35%). Among the infiltrating tumors (83%), the (median) thickness was 1.07 mm (women, 0.90 mm; men, 1.21 mm). Anatomopathological ulceration (AU) and a mitotic rate ≥1 mitosis/mm2 (HMR) were recorded in 27% of patients. Patients with regional disease constituted 12% of the population. The most common stage was IA (34%). Melanoma-specific survival (MSSV) decreased significantly with thickness, presence of AU, HMR, and sentinel lymph node disease. These four variables were independent prognostic factors. The five-year MSSV varied between 100% (stage IA) and 39% (stage IIIC). CONCLUSIONS: The characteristics of the patients were similar to those published in datasets from continental Europe, although the pigmentary features were darker in those originating from Macaronesia. The prognostic parameters described in the 7th edition of the American Joint Committee on Cancer (AJCC) independently predict MSSV in our patients.

MC1R gene variants and sporadic malignant melanoma susceptibility in the Canary Islands population.

Several MC1R variants are associated with increased risk of malignant melanoma (MM) in a variety of populations. We aim to examine the influence of the MC1R variants (RHC: D84E, R151C, R160W; NRHC: V60L, R163Q and the synonymous polymorphism T314T) on the MM risk in a population from the Canary Islands. Overall, 1,046 Caucasian individuals were included in the study. A thousand of them were genotyped for MC1R variants: 509 were sporadic MM patients and 491 were healthy control subjects from general population. The analysis was adjusted for age, sex, hair colour, eye colour, skin phototype and ancestry. We found that carriers of the R151C and R163Q variants were at an increased risk for melanoma OR 2.76 (1.59-4.78) and OR 5.62 (2.54-12.42), respectively. The risk of carrying RHC variants was 3.04 (1.90-4.86). Current study confirms the increased MM risk for R151C carriers. It also supports the association between R163Q variant and MM risk in the population on the Canary Islands, as opposed to reported on northern populations. These results highlight the importance of the sample population selection in this kind of studies.

A new method for the prediction of cervical node metastases in squamous cell carcinoma of the oral cavity: a combination of Martínez-Gimeno Scoring System and clinical palpation.

AIMS: Evaluation of the accuracy of palpation, CT scan and Martínez-Gimeno Score System in the assessment of neck nodes metastasis in squamous cell carcinoma of the oral cavity. DESIGN: This is a prospective triple blind study performed in 40 consecutive patients with squamous cell carcinoma of the oral cavity. PATIENTS: 40 consecutive patients suffering primary oral squamous cell carcinoma, without any treatment before surgery, palpation or CT Scan. RESULTS: 40% of the cases showed metastasis in pathological study. Sensitivity was 100%, 94% and 75% for MGSS 13, CT scan and palpation, respectively. Specificity was 83%, 38% and 25-50% for palpation, CT scan and MGSS 13-17, respectively. Negative predictive result values were 100%, 90% and 83% for MGSS 13, CT Scan and palpation. The logistic regression analysis showed an independent predictor factor for palpation (p=0.001) and MGSS (p=0.01). The combination of MGSS and clinical palpation allowed a new design for evaluating neck metastasis in oral cancer. This method establishes 3 different groups at risk: 3 of very low (<2%), 2 of low risk (18-27%) and 1 of high risk (85%). CONCLUSIONS: MGSS predicts metastasis better than CT scan and palpation. Combination of MGSS and palpation improves the prediction of metastasis.