Genetic analysis of the GRM1 gene in human melanoma susceptibility

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.