title: Intron variants of the p53 gene are associated with increased risk for ovarian cancer but not in carriers of BRCA1 or BRCA2 germline mutations.
abstract: Two biallelic polymorphisms in introns 3 and 6 of the p53 gene were analysed for a possible risk-modifying effect for ovarian cancer. Germline DNA was genotyped from 310 German Caucasian ovarian cancer patients and 364 healthy controls. We also typed 124 affected and 276 unaffected female carriers with known deleterious BRCA1 or BRCA2 germline mutation from high-risk breast-ovarian cancer families. Genotyping was based on PCR and high-resolution gel electrophoresis. German ovarian cancer patients who carried the rare allele of the MspI restriction fragment length polymorphism (RELP) in intron 6 were found to have an overall 1.93-fold increased risk (95% confidence internal (CI) 1.27-2.91) which further increased with the age at diagnosis of 41-60 years (odds ratio (OR) 2.71, 95% CI 1.10-6.71 for 41-50 and OR 2.44, 95% CI 1.12-5.28 for 51-60). The 16 bp duplication polymorphism in intron 3 was in a strong linkage to the MspI RFLP. In BRCA1 or BRCA2 mutation carriers, no difference in allele frequency was observed for carriers affected or unaffected with ovarian cancer. Our data suggest that intronic polymorphisms of the p53 gene modify the risk for ovarian cancer patients but not in carriers with BRCA1 or BRCA2 mutations.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Ulm, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Wang-Gohrke
authors.forename: W
authors.initials: W
authors.lastname: Weikel
authors.forename: H
authors.initials: H
authors.lastname: Risch
authors.forename: D
authors.initials: D
authors.lastname: Vesprini
authors.forename: J
authors.initials: J
authors.lastname: Abrahamson
authors.forename: C
authors.initials: C
authors.lastname: Lerman
authors.forename: A
authors.initials: A
authors.lastname: Godwin
authors.forename: R
authors.initials: R
authors.lastname: Moslehi
authors.forename: O
authors.initials: O
authors.lastname: Olipade
authors.forename: J S
authors.initials: JS
authors.lastname: Brunet
authors.forename: E
authors.initials: E
authors.lastname: Stickeler
authors.forename: D G
authors.initials: DG
authors.lastname: Kieback
authors.forename: R
authors.initials: R
authors.lastname: Kreienberg
authors.forename: B
authors.initials: B
authors.lastname: Weber
authors.forename: S A
authors.initials: SA
authors.lastname: Narod
authors.forename: I B
authors.initials: IB
authors.lastname: Runnebaum
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024682:BRCA2 Protein; D016022:Case-Control Studies; D005260:Female; D019398:Genes, BRCA1; D016158:Genes, p53; D006580:Genetic Carrier Screening; D014644:Genetic Variation; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D007438:Introns / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors