title: Absence of BRCA/FMR1 correlations in women with ovarian cancers.
abstract: Previously reported findings in Austrian BRCA1/2 mutation carriers suggested a possible dependency of embryos with BRCA1/2 mutations on so-called low alleles of the fragile X mental retardation 1 (FMR1) gene, characterized by less than 26 CGG repeats (CGG(n<26)). The hypothesis arose from a study reporting highly statistically significant enrichment of low FMR1 alleles, significantly exceeding low allele prevalence in a general population, suggesting embryo lethality of BRCA1/2 mutations, "rescued" by presence of low FMR1 alleles. Such a dependency would also offer an explanation for the so-called "BRCA-paradox," characterized by BRCA1/2 deficient embryonic tissues being anti-proliferative (thereby potentially causing embryo-lethality) but proliferative in malignant tumors, including breast and ovarian cancers. Follow up investigations by other investigators, however, at most demonstrated trends towards enrichment but, mostly, no enrichment at all, raising questions about the original observation and hypothesis. We in this study, therefore, investigated CGGn of the FMR1 gene of 86 anonymized DNA samples from women with various forms of ovarian cancer, and were unable to demonstrate differences in prevalence of low FMR1 alleles either between positive and negative ovarian cancer patients for BRCA1/2 or between ovarian cancer patients and reported rates in non-cancer populations. This raises further questions about a suggested dependency between BRCA1/2 and FMR1, but also raises the possibility that investigated Austrian BRCA1/2 carrier populations differ from those in other countries. Either only selected BRCA1/2 mutations, therefore, interact with low FMR1 alleles or the Austrian data reflect only coincidental observations.
authors.affiliation: Center for Human Reproduction, New York, New York, United States of America; Foundation for Reproductive Medicine, New York, New York, United States of America.
authors.forename: Norbert
authors.initials: N
authors.lastname: Gleicher
authors.affiliation: Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, University of British Columbia, Vancouver, British Columbia, Canada; OvCaRe Gynecologic Tissue Bank, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: McAlpine
authors.affiliation: OvCaRe Gynecologic Tissue Bank, BC Cancer Agency, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.affiliation: Center for Human Reproduction, New York, New York, United States of America.
authors.forename: Vitaly A
authors.initials: VA
authors.lastname: Kushnir
authors.affiliation: Center for Human Reproduction, New York, New York, United States of America.
authors.forename: Ho-Joon
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Center for Human Reproduction, New York, New York, United States of America.
authors.forename: Yan-Guang
authors.initials: YG
authors.lastname: Wu
authors.affiliation: Center for Human Reproduction, New York, New York, United States of America.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Lazzaroni-Tealdi
authors.affiliation: Center for Human Reproduction, New York, New York, United States of America; Foundation for Reproductive Medicine, New York, New York, United States of America.
authors.forename: David H
authors.initials: DH
authors.lastname: Barad
mesh_terms: D000483:Alleles; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human