title: CYP2D6 genetic polymorphisms are associated with susceptibility to pituitary tumors.
abstract: Several polymorphisms of drug-metabolizing enzymes have been implicated in the susceptibility to tumor development. The role of the CYP2D6, GSTM1 and GSTT1 genes has been extensively studied, with alleles conferring different metabolic efficiencies and tumor risk. We studied the relationship between the main polymorphisms of these genes and the susceptibility to develop pituitary tumors, by performing a case-control study comprising 235 patients and 256 controls which were genotyped by means of PCR-RFLP based assays. Frequencies of the CYP2D6*1 and of the poor metabolizer allele CYP2D6*4, were determined along with the frequencies of the GSTM1 and GSTT1 null genotypes. CYP2D6 genotype frequencies were similar in patients and controls (p=0.087). CYP2D6*1 and CYP2D6*4 allele frequencies were 83.8%, 16.2% in cases and 78.3%, 21.7% in controls, showing a significant difference between the two groups (p=0.012). There were no significant differences between the frequencies of the GSTM1 and GSTT1 null genotypes in both groups. No association was found between histological type and any of the studied polymorphisms. Our data suggest an association of the CYP2D6*1 allele and the susceptibility to pituitary adenomas, which could be due to an increased metabolism of unidentified procarcinogens or to linkage disequilibrium with another gene involved in pituitary tumorigenesis.
authors.affiliation: Serviço de Endocrinologia, Diabetes e Metabolismo, Hospitais da Universidade de Coimbra, Faculdade de Medicina, Coimbra.
authors.forename: Leonor
authors.initials: L
authors.lastname: Gomes
authors.forename: Manuel C
authors.initials: MC
authors.lastname: Lemos
authors.forename: Isabel
authors.initials: I
authors.lastname: Paiva
authors.forename: Cristina
authors.initials: C
authors.lastname: Ribeiro
authors.forename: Manuela
authors.initials: M
authors.lastname: Carvalheiro
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Regateiro
mesh_terms: D000236:Adenoma / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D020868:Gene Silencing; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010911:Pituitary Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D012189:Retrospective Studies
chemical_list: D019389:Cytochrome P-450 CYP2D6; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1