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UGT1A1*28 polymorphism in ovarian cancer patients

Authors: Erika, Cecchin; Antonio, Russo; Giuseppe, Corona; Elio, Campagnutta; Luca, Martella; Mauro, Boiocchi; Giuseppe, Toffoli;

UGT1A1*28 polymorphism in ovarian cancer patients

Abstract

(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.

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Keywords

Ovarian Neoplasms, Heterozygote, Polymorphism, Genetic, Homozygote, Loss of Heterozygosity, Estrogens, Irinotecan, Antineoplastic Agents, Phytogenic, Polymerase Chain Reaction, Odds Ratio, Humans, Protein Isoforms, Regression Analysis, Camptothecin, Female, Glucuronosyltransferase, UGT1A1 Enzyme

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
23
Average
Top 10%
Top 10%
Related to Research communities
Cancer Research
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