title: X chromosome inactivation pattern in BRCA gene mutation carriers.
abstract: An association of preferential X chromosome inactivation (XCI) with BRCA gene status and breast/ovarian cancer risk has been reported. We evaluated XCI in a large group of BRCA mutation carriers compared to non-carriers and investigated associations between preferential XCI (⩾90:10) and age, mutated gene, cancer development and chemotherapy. XCI was analysed by human androgen receptor (HUMARA) assay and pyrosequencing in 437 BRCA1 or BRCA2 mutation carriers and 445 age-matched controls. The distribution of XCI patterns in the two groups was compared by logistic regression analysis. The association between preferential XCI and selected variables was investigated in both univariate and multivariate fashion. In univariate analyses preferential XCI was not significantly associated with the probability of being a BRCA mutation carrier, nor with cancer status, whereas chemotherapeutic regime and age both showed a significant association. In multivariate analysis only age maintained significance (odds ratio, 1.056; 95% confidence interval, 1.016-1.096). Our findings do not support the usefulness of XCI analysis for the identification of BRCA mutation carriers and cancer risk assessment. The increasing preferential XCI frequency with ageing and the association with chemotherapy justify extending the investigation to other categories of female cancer patients to identify possible X-linked loci implicated in cell survival.
authors.affiliation: Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Siranoush
authors.initials: S
authors.lastname: Manoukian
authors.forename: Paolo
authors.initials: P
authors.lastname: Verderio
authors.forename: Silvia
authors.initials: S
authors.lastname: Tabano
authors.forename: Patrizia
authors.initials: P
authors.lastname: Colapietro
authors.forename: Sara
authors.initials: S
authors.lastname: Pizzamiglio
authors.forename: Francesca R
authors.initials: FR
authors.lastname: Grati
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Calvello
authors.forename: Bernard
authors.initials: B
authors.lastname: Peissel
authors.forename: John
authors.initials: J
authors.lastname: Burn
authors.forename: Valeria
authors.initials: V
authors.lastname: Pensotti
authors.forename: Claudia
authors.initials: C
authors.lastname: Allemani
authors.forename: Silva M
authors.initials: SM
authors.lastname: Sirchia
authors.forename: Paolo
authors.initials: P
authors.lastname: Radice
authors.forename: Monica
authors.initials: M
authors.lastname: Miozzo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D002277:Carcinoma / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D011237:Predictive Value of Tests; D011944:Receptors, Androgen / Q000032:analysis / Q000235:genetics; D049951:X Chromosome Inactivation / Q000235:genetics*; D055815:Young Adult
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen