title: Adiposity is associated with p53 gene mutations in breast cancer.
abstract: Mutations in the p53 gene are among the most frequent genetic events in human cancer and may be triggered by environmental and occupational exposures. We examined the association of clinical and pathological characteristics of breast tumors and breast cancer risk factors according to the prevalence and type of p53 mutations. Using tumor blocks from incident cases from a case-control study in western New York, we screened for p53 mutations in exons 2-11 using the Affymetrix p53 Gene Chip array and analyzed case-case comparisons using logistic regression. The p53 mutation frequency among cases was 28.1 %; 95 % were point mutations (13 % of which were silent) and the remainder were single base pair deletions. Sixty seven percent of all point mutations were transitions; 24 % of them are G:C>A:T at CpG sites. Positive p53 mutation status was associated with poorer differentiation (OR, 95 % CI 2.29, 1.21-4.32), higher nuclear grade (OR, 95 % CI 1.99, 1.22-3.25), and increased Ki-67 status (OR, 95 % CI 1.81, 1.10-2.98). Cases with P53 mutations were more likely to have a combined ER-positive and PR-negative status (OR, 95 % CI 1.65, 1.01-2.71), and a combined ER-negative and PR-negative status (OR, 95 % CI 2.18, 1.47-3.23). Body mass index >30 kg/m(2), waist circumference >79 cm, and waist-to-hip ratio >0.86 were also associated with p53 status; obese breast cancer cases are more likely to have p53 mutations (OR, 95 % CI 1.78, 1.19-2.68). We confirmed that p53 mutations are associated with less favorable tumor characteristics and identified an association of p53 mutation status and adiposity.
authors.affiliation: Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Ochs-Balcom
authors.affiliation: Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA. catalin.marian@osumc.edu.|Biochemistry Department, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania. catalin.marian@osumc.edu.
authors.forename: Catalin
authors.initials: C
authors.lastname: Marian
authors.affiliation: Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
authors.affiliation: Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Theodore M
authors.initials: TM
authors.lastname: Brasky
authors.affiliation: Lombardi Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Goerlitz
authors.affiliation: Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA.|Department of Community Health and Social Medicine, School of Biomedical Education, The City College of New York, New York, NY, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Trevisan
authors.affiliation: Division of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Edge
authors.affiliation: Division of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Winston
authors.affiliation: Lombardi Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Berry
authors.affiliation: Lombardi Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Bhaskar V
authors.initials: BV
authors.lastname: Kallakury
authors.affiliation: Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA.
authors.forename: Jo L
authors.initials: JL
authors.lastname: Freudenheim
authors.affiliation: Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Shields
mesh_terms: D050154:Adiposity; D000328:Adult; D000368:Aged; D000483:Alleles; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D016158:Genes, p53; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009518:New York / Q000453:epidemiology; D011159:Population Surveillance; D012307:Risk Factors; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor
keywords: Adiposity; Breast cancer; p53 mutation