title: Genetic analysis of the GRM1 gene in human melanoma susceptibility.
abstract: Data obtained from a mouse model indicated that the ectopic expression of the Grm1 gene is sufficient for transforming melanocytes and causing malignant melanoma in vivo. In addition, it has also been documented that the GRM1 gene is aberrantly expressed in human melanomas. Here we have performed a genetic association study to elucidate whether the GRM1 gene contributes to human melanoma susceptibility. To carry out this study, we initially genotyped 250 melanoma patients and 329 nonselected and nonrelated controls with three single nucleotide polymorphisms, rs854145, rs362962 and rs6923492, located in the intron 1, intron 4 and exon 10 of the GRM1 gene, respectively. To perform sample genotyping, we used pyrosequencing techniques. Regarding rs854145 and rs6923492, there were no differences in genotypic distribution or allelic frequency between patients and controls. However, we observed (i) a higher frequency of patients carrying the C allele of rs362962 than in controls (OR=1.40, CI=[1.01-1.95], P=0.045), and (ii) that difference became greater in a subgroup of patients with a low level of sun exposure and tumours located on the trunk and extremities (OR=2.10, CI=[1.26-3.51], P=0.0039). To confirm these observations, the sample size of both patient and control groups was increased. In total, 464 patients and 561 controls were genotyped for the rs362962 polymorphism. Only the second observation was confirmed (OR=1.69, CI=[1.16-2.47], P=0.0064). Our results suggest that the GRM1 gene may contribute to melanoma susceptibility in that specific group of patients.
authors.affiliation: Servicio de Dermatología, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Ortiz
authors.forename: Francisco
authors.initials: F
authors.lastname: Vanaclocha
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Bran
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Esquivias
authors.forename: José Luis
authors.initials: JL
authors.lastname: López-Estebaranz
authors.forename: Manuel
authors.initials: M
authors.lastname: Martín-González
authors.forename: Itziar
authors.initials: I
authors.lastname: Arrue
authors.forename: Diana
authors.initials: D
authors.lastname: García-Romero
authors.forename: Carolina
authors.initials: C
authors.lastname: Ochoa
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Perez
authors.forename: Agustin
authors.initials: A
authors.lastname: Ruiz
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Real
mesh_terms: D016022:Case-Control Studies; D005121:Extremities; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*; D013472:Sunlight / Q000009:adverse effects
chemical_list: D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1