title: The CYP1A1 Ile462Val polymorphism and platinum resistance of epithelial ovarian neoplasms.
abstract: The role of estrogens in ovarian carcinogenesis and progression of ovarian cancer is unclear. Cytochrome P450 is involved in estrogen metabolism, and polymorphisms have been associated with functional changes and risk for ovarian cancer. In this study, we investigated the impact of the CYP1A1 Ile462Val polymorphism upon tumor risk and disease progression in ovarian cancer patients. One hundred and eleven ovarian cancer patients who had been treated at the University Hospital of Essen between 1999 and 2007 and 119 age-matched healthy female controls were enrolled in this study. Genotyping was performed using PCR-RFLP. The distribution of genotypes was statistically significant different between ovarian cancer patients and healthy controls. We observed a significant association of the Ile allele with ovarian cancer (OR 2.6, 95% CI 1.5-4.7, p = 0.001). Clinical parameters such as overall survival, FIGO stage, grading, and age at diagnosis did not differ significantly. We observed a statistically significant association between the 462Val allele and platinum resistance, which was defined as a time interval < 6 months to disease progression after administration of a platinum-based primary chemotherapy (OR 5.9, 95% CI 1.5-23.2, p = 0.005). We observed a significant association between the presence of the 462Ile allele with ovarian cancer. While there is uncertainty about the potential involvement of CYP1A1 in the metabolism of platinum-containing agents, our findings suggest an association between the 462Val allele and the development of platinum resistance in ovarian tumors. If confirmed in a larger, independent collective, our findings would have important relevance with respect to the clinical consequences for the primary chemotherapy of ovarian cancer patients.
authors.affiliation: Institute of Pharmacogenetics, Medical Faculty, University of Duisburg-Essen, Essen, Germany. martin.heubner@uk-essen.de
authors.forename: Martin
authors.initials: M
authors.lastname: Heubner
authors.forename: Pauline
authors.initials: P
authors.lastname: Wimberger
authors.forename: Kathrin
authors.initials: K
authors.lastname: Riemann
authors.forename: Sabine
authors.initials: S
authors.lastname: Kasimir-Bauer
authors.forename: Friedrich
authors.initials: F
authors.lastname: Otterbach
authors.forename: Rainer
authors.initials: R
authors.lastname: Kimmig
authors.forename: Winfried
authors.initials: W
authors.lastname: Siffert
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D019363:Cytochrome P-450 CYP1A1