UGT1A1*28 polymorphism in ovarian cancer patients.
(Uridino-diphosphate)glucuronosyl-transferase enzyme 1A1 isoform (UGT1A1) is involved in glucuronidation of antineoplastic drugs such as SN38, the active metabolite of irinotecan, as well as estrogens and their metabolites. UGT1A1*28 polymorphism decreases UGT1A1 expression and could alter estrogens disposition influencing tumour growth in hormone sensitive tissues. The UGT1A1*28 distribution among an ovarian cancer patient (OCP) population of 217 mono-institutional individuals was investigated to clarify its possible involvement in the pathogenesis and chemotherapy of ovarian cancer. Data were compared with those of 205 female healthy blood donors. In 160 patients also the tumour tissue was genotyped to describe the occurrence of loss of heterozygosity (LOH). A PCR based assay followed by automated fragment analysis was used. Odds ratios (OR), and 95% confidence intervals (95% CI), were computed by a multiple logistic regression model using as dependent variable in a case-control or in a case-case approach the histological classification. No significant prevalence of the polymorphism was observed in the cases versus controls. In a case-case approach, a higher frequency of the polymorphism was observed in patients with mucinous tumours (6/11, 54.6%) compared to non-mucinous (30/206, 14.6%) (p=0.009, OR=7.20; 95% CI 2.06-25.19). LOH was observed in 12 cases out of 160 (7.5%) and was associated with non-mucinous tumours, 10 (83.3%) cases determined a retention of the wild-type allele. In conclusion, the prevalence of UGT1A1*28 found in mucinous OCP could suggest a role in the development of specific histologic sub-groups and could become a marker to be considered when planning ovarian cancer chemotherapy.
Cecchin
Erika
E
Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico, National Cancer Institute, 33081 Aviano, Italy.
Russo
Antonio
A
Corona
Giuseppe
G
Campagnutta
Elio
E
Martella
Luca
L
Boiocchi
Mauro
M
Toffoli
Giuseppe
G
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D000077146:Irinotecan; D019656:Loss of Heterozygosity; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020033:Protein Isoforms; D012044:Regression Analysis; D000099148:UGT1A1 Enzyme
D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D004967:Estrogens; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D020033:Protein Isoforms; D000099148:UGT1A1 Enzyme