Microsomal epoxide hydrolase polymorphism and susceptibility to ovarian cancer

• Published in: Cancer letters 2002-03, Vol.177 (1), p.75-81
• Main Authors: Baxter, S.W, Choong, D.Y.H, Campbell, I.G
• Format: Article
• Language: English
• Subjects: Adenocarcinoma, Mucinous - enzymology; Adenocarcinoma, Mucinous - genetics; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Cancer predisposition; Carcinoma, Endometrioid - enzymology; Carcinoma, Endometrioid - genetics; Case-Control Studies; Cystadenocarcinoma, Serous - enzymology; Cystadenocarcinoma, Serous - genetics; Disease Susceptibility; DNA Primers; Enzymes; Epoxide Hydrolases - genetics; Female; Female genital diseases; Genes; Genotype; Genotype & phenotype; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Microsomal epoxide hydrolase; Microsomes - enzymology; Middle Aged; Neoplasms, Glandular and Epithelial - enzymology; Neoplasms, Glandular and Epithelial - genetics; Ovarian cancer; Ovarian Neoplasms - enzymology; Ovarian Neoplasms - genetics; Polymerase Chain Reaction; Polymorphism; Polymorphism, Genetic; Retrospective Studies; Tumors
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(01)00782-0

Polymorphic variants of microsomal epoxide hydrolase (mEPHX) with altered enzyme activity have been associated with an increased risk for ovarian cancer. We assessed the frequency of exon 3 and exon 4 variants of mEPHX among 291 ovarian cancers and 257 controls from a UK-based population. The distribution of the exon 3 alleles among both the cancer and control groups was significantly different from that expected under Hardy–Weinberg equilibrium suggesting that the PCR restriction fragment length polymorphism (PCR-RFLP) genotyping assay might be flawed. The codon 113 polymorphism was reassessed using a two-color allele-specific PCR-based assay. We found that a codon 119 G>A polymorphism, present in 20% of the British population and linked to the wild-type exon 3 allele, resulted in some Tyr113/His113 heterozygotes being falsely classified as His113/His113 homozygotes when using the PCR-RFLP assay. Consequently, we reassessed all our codon 113 data using the new allele-specific assay. We found no evidence of an association of ovarian cancer risk with the exon 3 Tyr113>His113 variant. Similarly the frequencies of the exon 4 His139>Arg139 genotypes were not significantly different between cases and controls. Stratifying the genotyping data according to the predicted mEPHX activity revealed a highly significant decrease in high mEPHX activity among the serous ovarian cancers ( P=0.01) suggesting that high mEPHX activity may be protective for this histological sub-type. Furthermore previous disease association studies of exon 3 alleles which utilized the PCR-RFLP assay may be compromised by the existence of a codon 119 G>A polymorphism which may be common in Caucasian populations.