GSTM1 and CYP2D6 genotype frequencies in patients with pituitary tumours: effects on P53, ras and gsp.
We describe studies to determine if susceptibility to pituitary tumours is associated with the putatively high risk GSTM1 null and CYP2D6 EM genotypes. Frequency distributions of these genotypes were similar in cases and controls though the frequency of CYP2D6 PM and GSTM1 B tended to be lower (P = 0.072 and P = 0.095 respectively) in the tumour group. Immunopositivity for p53 was found in 18/97 tumours. In these samples GSTM1 null (39%) and CYP2D6 EM (56%) frequencies were not different to those in controls. The frequencies of CYP2D6 PM and GSTM1 B in the p53 immunonegative tumours tended to be lower (P = 0.055 and P = 0.1185 respectively) than in controls. Mutations in gsp and ras were studied using the polymerase chain reaction and allele specific oligonucleotide analysis. Eight of 19 somatotrophinomas demonstrated mutations in gsp; frequencies of GSTM1 null and CYP02D6 EM were similar to controls. No ras mutations were identified in 55-tumour studies. The data indicate the GSTM1 null and CYP2D6 EM genotypes are not associated with altered expression of p53 or, mutation of gsp and ras in these adenomas and, suggest the CYP2D6 PM genotype is associated with a reduced risk of pituitary adenomas and, that GSTM1*B confers greater protection than GSTM1*A.
Perrett
C W
CW
Department of Medicine, School of Postgraduate Medicine, Keele University, North Staffordshire Hospital/Stoke-on-Trent, UK.
Clayton
R N
RN
Pistorello
M
M
Boscaro
M
M
Scanarini
M
M
Bates
A S
AS
Buckley
N
N
Jones
P
P
Fryer
A A
AA
Gilford
J
J
D000328:Adult; D000368:Aged; D000483:Alleles; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D011905:Genes, ras; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics*; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009154:Mutation; D010911:Pituitary Neoplasms / Q000201:enzymology* / Q000235:genetics*; D010940:Plant Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
C088852:GSP-1 protein, Triticum aestivum; D007527:Isoenzymes; D010940:Plant Proteins; D016159:Tumor Suppressor Protein p53; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; D005982:Glutathione Transferase; D019204:GTP-Binding Proteins