ABSTRACT
As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pathway have been successfully genotyped using a SNP array. Five hundred and ninety MM cases and 507 controls were analyzed in a discovery phase I. Ten candidate SNPs based on a p-value threshold of 0.01 were identified. Two of them, rs35414 (SLC45A2) and rs2069398 (SILV/CKD2), were statistically significant after conservative Bonferroni correction. The best six SNPs were further tested in an independent Spanish series (624 MM cases and 789 controls). A novel SNP located on the SLC45A2 gene (rs35414) was found to be significantly associated with melanoma in both phase I and phase II (P<0.0001). None of the other five SNPs were replicated in this second phase of the study. However, three SNPs in TYR, SILV/CDK2 and ADAMTS20 genes (rs17793678, rs2069398 and rs1510521 respectively) had an overall p-value<0.05 when considering the whole DNA collection (1214 MM cases and 1296 controls). Both the SLC45A2 and the SILV/CDK2 variants behave as protective alleles, while the TYR and ADAMTS20 variants seem to function as risk alleles. Cumulative effects were detected when these four variants were considered together. Furthermore, individuals carrying two or more mutations in MC1R, a well-known low penetrance melanoma-predisposing gene, had a decreased MM risk if concurrently bearing the SLC45A2 protective variant. To our knowledge, this is the largest study on Spanish sporadic MM cases to date.
Subject(s)
Antigens, Neoplasm/genetics , Genetic Predisposition to Disease , Melanoma/genetics , Membrane Transport Proteins/genetics , Oligonucleotide Array Sequence Analysis , Polymorphism, Single Nucleotide , Adult , Aged , Aged, 80 and over , Female , Gene Frequency , Genetic Variation , Genotype , Haplotypes , Humans , Male , Melanoma/epidemiology , Middle Aged , Mutation , Risk , SpainABSTRACT
La queratodermia acuagénica es un proceso infrecuente caracterizado por la aparición de lesiones en las palmas de las manos pocos minutos después del contacto con el agua, y que desaparecen al poco tiempo de su secado. Los casos publicados corresponden a mujeres, fundamentalmente durante la adolescencia. Presentamos el caso de un varón con lesiones clínicamente superponibles a una queratodermia acuagénica pero con distribución en el dorso de ambas manos y en la cara anterior de muñeca. Estas características no se habían descrito hasta el momento en la literatura científica. Se revisan los casos previamente descritos y se establecen varios diagnósticos diferenciales, como las lesiones palmares inducidas por el rofecoxib o las que aparecen en la fibrosis quística
Aquagenic keratoderma is an infrequent condition characterized by the appearance of lesions on the palms of the hands a few minutes after contact with water; these lesions vanish a short time after they dry. Published cases were primarily in adolescent females. We present the case of a male patient with lesions that clinically corresponded to aquagenic keratoderma, except that they were distributed on the backs of both hands and on the anterior face of the wrist. These characteristics had not been described in the literature prior to this case. Previously described cases were reviewed and several differential diagnoses were established, such as rofecoxib-induced palmar lesions, or those appearing in cystic fibrosis
Subject(s)
Male , Adult , Humans , Keratoderma, Palmoplantar/diagnosis , Keratoderma, Palmoplantar/therapy , Diagnosis, Differential , Silicon Compounds/therapeutic use , Aluminum/therapeutic use , Botulinum Toxins, Type A/therapeutic use , Eccrine Glands/pathology , Hand/pathology , Hand Dermatoses/diagnosis , Hand Dermatoses/therapyABSTRACT
Aquagenic keratoderma is an infrequent condition characterized by the appearance of lesions on the palms of the hands a few minutes after contact with water; these lesions vanish a short time after they dry. Published cases were primarily in adolescent females. We present the case of a male patient with lesions that clinically corresponded to aquagenic keratoderma, except that they were distributed on the backs of both hands and on the anterior face of the wrist. These characteristics had not been described in the literature prior to this case. Previously described cases were reviewed and several differential diagnoses were established, such as rofecoxib-induced palmar lesions, or those appearing in cystic fibrosis.
Subject(s)
Hand Dermatoses/pathology , Keratosis/pathology , Skin Diseases, Papulosquamous/pathology , Adult , Humans , MaleABSTRACT
El diagnóstico de enfermedad de Lafora se basa en la sintomatología clínica y en la detección histológica de unas inclusiones intracitoplasmáticos PAS positivas denominadas cuerpos de Lafora. A pesar de que esta entidad no cursa con manifestaciones cutáneas, la participación del dermatólogo y del dermatopatólogo es importante, pues la biopsia de la piel axilar es el procedimiento diagnóstico más rentable. En esta localización los cuerpos de Lafora se detectan principalmente en las células periféricas ductales de los conductos ecrinos y en las células mioepiteliales de las glándulas apocrinas. Presentamos este hallazgo en una mujer de 17 años (AU)
