title: Assessment of TP53 Polymorphisms and MDM2 SNP309 in Premenopausal Breast Cancer Risk.
abstract: Germline polymorphic variants in cancer predisposition genes such as TP53 have been shown to impact the risk of premenopausal cancer. Accordingly, the aim of this study was to assess the spectrum of polymorphisms in TP53 and its negative regulatory gene, MDM2 (SNP309:T>G) in patients with premenopausal breast cancer. Our findings in a cohort of 40 female patients demonstrate no significant correlation between the studied polymorphisms and risk of premenopausal breast cancer. Although one polymorphism is found in high frequency in this cohort (rs1800372:A>G, 9.0%), it was not associated with the risk of developing cancer before the age of 35 years in an extended cohort of 1,420 breast cancer cases. Functional studies of the rs1800372:A>G polymorphic allele reveal that it does not affect p53 transactivation function. Further study of variants or mutations in other cancer susceptibility genes is warranted to refine our understanding of the germline contribution to premenopausal breast cancer susceptibility.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.|Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.|Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: Nardin
authors.initials: N
authors.lastname: Samuel
authors.affiliation: Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Badr
authors.initials: B
authors.lastname: Id Said
authors.affiliation: Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Tanya
authors.initials: T
authors.lastname: Guha
authors.affiliation: Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Ana
authors.initials: A
authors.lastname: Novokmet
authors.affiliation: The Centre for Applied Genomics, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Weili
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Genetics, Institute for Cancer Research, The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
authors.forename: Laxmi
authors.initials: L
authors.lastname: Silwal-Pandit
authors.affiliation: Department of Genetics, Institute for Cancer Research, The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børrsen-Dale
authors.affiliation: Department of Genetics, Institute for Cancer Research, The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
authors.forename: Anita
authors.initials: A
authors.lastname: Langerød
authors.affiliation: Oncology Discovery and Early Development, AbbVie Inc, Redwood City, California.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.|Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Pediatrics, University of Toronto, Toronto, Ontario.
authors.forename: David
authors.initials: D
authors.lastname: Malkin
mesh_terms: D017668:Age of Onset; D000483:Alleles; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D017697:Premenopause; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012306:Risk; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2
keywords: MDM2; PIN3; TP53; polymorphism; pre-menopausal breast cancer