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. 2014 Jun 17;9(6):e99893.
doi: 10.1371/journal.pone.0099893. eCollection 2014.

Prevalence of the TP53 p.R337H mutation in breast cancer patients in Brazil

Juliana Giacomazzi  1 , Marcia S Graudenz  2 , Cynthia A B T Osorio  3 , Patricia Koehler-Santos  4 , Edenir I Palmero  5 , Marcelo Zagonel-Oliveira  6 , Rodrigo A D Michelli  5 , Cristovam Scapulatempo Neto  5 , Gabriela C Fernandes  5 , Maria Isabel W S Achatz  7 , Ghyslaine Martel-Planche  8 , Fernando A Soares  3 , Maira Caleffi  9 , José Roberto Goldim  10 , Pierre Hainaut  11 , Suzi A Camey  12 , Patricia Ashton-Prolla  13
Affiliations

Prevalence of the TP53 p.R337H mutation in breast cancer patients in Brazil

Juliana Giacomazzi et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: An academic grant from GlaxoSmithKline Oncology (Ethnic Research Initiative Grant Award 2009) provided partial funding for this study. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Pedigrees of mutation-positive probands from group 1.
Blackened symbols represent cancer-affected relatives. An arrow indicates the proband. Dx: age at diagnosis; WT: wild-type; WT: wild-type; *TP53 (p.R337H) mutation carriers and negative for BRCA1/2; **TP53 (p.R337H) and BRCA1 negative and BRCA2 mutation carrier; ***TP53 (p.R337H) negative an BRCA1/2 negative.
Figure 2
Figure 2. The geographic distribution of breast cancer-affected women in group 2 whose city of residence was known (n = 657).
Legend: Blue dots, red triangles and green stars represent the cities of residence of women who are homozygous normal, heterozygous, and homozygous mutant p.R337H, respectively.
See this image and copyright information in PMC

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