title: Prevalence of the TP53 p.R337H mutation in breast cancer patients in Brazil.
abstract: Germline TP53 mutations predispose individuals to multiple cancers and are associated with Li-Fraumeni/Li-Fraumeni-Like Syndromes (LFS/LFL). The founder mutation TP53 p.R337H is detected in 0.3% of the general population in southern Brazil. This mutation is associated with an increased risk of childhood adrenal cortical carcinoma (ACC) but is also common in Brazilian LFS/LFL families. Breast Cancer (BC) is one of the most common cancers diagnosed in TP53 mutation carriers. We have assessed the prevalence of p.R337H in two groups: (1) 59 BC affected women with a familial history (FH) suggestive of hereditary cancer syndrome but no LFS/LFL features; (2) 815 BC affected women unselected for cancer FH, diagnosed with BC at or before age 45 or at age 55 or older. Among group 1 and group 2 patients, 2/59 (3.4%, CI95%: 0.4%-11.7%) and 70/815 (8.6%, CI95%: 6.8%-10.7%), respectively, were p.R337H carriers in the germline. The prevalence of p.R337H was higher in women diagnosed with BC at or before age 45 (12.1%, CI95%: 9.1%-15.8%) than at age 55 or older (5.1%, CI95%: 3.2%-7.7%), p<0.001). The Brazilian founder p.R337H haplotype was detected in all carriers analysed. These results suggest that inheritance of p.R337H may significantly contribute to the high incidence of BC in Brazil, in addition to its recently demonstrated impact on the risk of childhood ACC.
authors.affiliation: Genomic Medicine Laboratory, Experimental Research Centre, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil; Post-Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Giacomazzi
authors.affiliation: Post-Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil; Pathology Service, HCPA, Porto Alegre, Rio Grande do Sul, Brazil and Instituto de Patologia, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Marcia S
authors.initials: MS
authors.lastname: Graudenz
authors.affiliation: Pathology Service, Hospital do Câncer AC Camargo (HCACC), São Paulo, São Paulo, Brazil.
authors.forename: Cynthia A B T
authors.initials: CA
authors.lastname: Osorio
authors.affiliation: Protein and Molecular Analysis Laboratory, Experimental Research Centre, HCPA, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Koehler-Santos
authors.affiliation: Molecular Oncology Research Centre, Hospital do Câncer de Barretos, Barretos, São Paulo, Brazil.
authors.forename: Edenir I
authors.initials: EI
authors.lastname: Palmero
authors.affiliation: National Institute of Populational Medical Genetics (INAGEMP), UFRGS, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Zagonel-Oliveira
authors.affiliation: Molecular Oncology Research Centre, Hospital do Câncer de Barretos, Barretos, São Paulo, Brazil.
authors.forename: Rodrigo A D
authors.initials: RA
authors.lastname: Michelli
authors.affiliation: Molecular Oncology Research Centre, Hospital do Câncer de Barretos, Barretos, São Paulo, Brazil.
authors.forename: Cristovam
authors.initials: C
authors.lastname: Scapulatempo Neto
authors.affiliation: Molecular Oncology Research Centre, Hospital do Câncer de Barretos, Barretos, São Paulo, Brazil.
authors.forename: Gabriela C
authors.initials: GC
authors.lastname: Fernandes
authors.affiliation: Oncogenetics Department, HCACC, São Paulo, São Paulo, Brazil.
authors.forename: Maria Isabel W S
authors.initials: MI
authors.lastname: Achatz
authors.affiliation: International Agency for Research on Cancer (IARC), Lyon, Rhone, France.
authors.forename: Ghyslaine
authors.initials: G
authors.lastname: Martel-Planche
authors.affiliation: Pathology Service, Hospital do Câncer AC Camargo (HCACC), São Paulo, São Paulo, Brazil.
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Hospital Moinhos de Vento, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Maira
authors.initials: M
authors.lastname: Caleffi
authors.affiliation: Bioethics Research Laboratory, HCPA, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: José Roberto
authors.initials: JR
authors.lastname: Goldim
authors.affiliation: International Agency for Research on Cancer (IARC), Lyon, Rhone, France; International Prevention Research Institute, Lyon, Rhone, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Hainaut
authors.affiliation: Department of Statistics, Institute of Mathematics, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Suzi A
authors.initials: SA
authors.lastname: Camey
authors.affiliation: Genomic Medicine Laboratory, Experimental Research Centre, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil; Post-Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil; National Institute of Populational Medical Genetics (INAGEMP), UFRGS, Porto Alegre, Rio Grande do Sul, Brazil; Post-Graduate Program in Genetics and Molecular Biology, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ashton-Prolla
mesh_terms: D000328:Adult; D001938:Brazil / Q000453:epidemiology; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D015995:Prevalence; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53