title: PPM1D mutations in circulating white blood cells and the risk for ovarian cancer.
abstract: We compared the frequency of PPM1D mutation in the white blood cells from 1295 ovarian cancer case patients and 834 control subjects. We found a truncating mutation in 20 case patients vs 1 control subject (odds ratio [OR] = 13.07; 95% confidence interval [CI] = 1.75 to 97.55; P < .001). The 12-year mortality of the PPM1D-positive case patients was higher than that of the PPM1D-negative case patients (hazard ratio = 2.02; 95% CI = 1.21 to 3.39; P = .007). Three of the 20 PPM1D carrier case patients had a past history of breast cancer compared with 29 of 1129 noncarriers (OR = 6.69; 95% CI = 1.86 to 24.11; P = .007). The lifetime risks for breast or ovarian cancer among female first-degree relatives of PPM1D mutation carriers were not increased compared with that of case patients without mutations. These observations suggest PPM1D mutations in the mosaic state predispose women to breast and ovarian cancer in the absence of a family history of cancer.
authors.affiliation: Affiliations of authors: Womens College Research Institute, Womens College Hospital (MRA, SAN), Dalla Lana School of Public Health (MRA, JM, SAN), Samuel Lunenfeld Research Institute (JM), University of Toronto, Toronto, Canada; Genome Quebec Innovation Centre, McGill University, Montreal, Canada (PL); Department of Gynecology-Oncology (BR), and Department of Medical Oncology (MM), Princess Margaret Hospital, Toronto, Canada; Department of Epidemiology and Public Health, School of Public Health, School of Medicine, Yale University, New Haven, CT (HR).
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Akbari
authors.forename: Pierre
authors.initials: P
authors.lastname: Lepage
authors.forename: Barry
authors.initials: B
authors.lastname: Rosen
authors.forename: John
authors.initials: J
authors.lastname: McLaughlin
authors.forename: Harvey
authors.initials: H
authors.lastname: Risch
authors.forename: Mark
authors.initials: M
authors.lastname: Minden
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
mesh_terms: D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D007962:Leukocytes / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D016016:Proportional Hazards Models; D000071636:Protein Phosphatase 2C; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C000607458:PPM1D protein, human; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C