Giacomazzi Juliana, Graudenz Marcia S, Osorio Cynthia A B T, Koehler-Santos Patricia, Palmero Edenir I, Zagonel-Oliveira Marcelo, Michelli Rodrigo A D, Scapulatempo Neto Cristovam, Fernandes Gabriela C, Achatz Maria Isabel W S, Martel-Planche Ghyslaine, Soares Fernando A, Caleffi Maira, Goldim José Roberto, Hainaut Pierre, Camey Suzi A, Ashton-Prolla Patricia
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.
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.
PLoS One. 2014 Jun 17;9(6):e99893. doi: 10.1371/journal.pone.0099893. eCollection 2014.
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.
种系TP53突变使个体易患多种癌症，并与李-弗劳梅尼/李-弗劳梅尼样综合征（LFS/LFL）相关。在巴西南部0.3%的普通人群中检测到奠基者突变TP53 p.R337H。该突变与儿童肾上腺皮质癌（ACC）风险增加相关，但在巴西LFS/LFL家族中也很常见。乳腺癌（BC）是TP53突变携带者中最常见的诊断癌症之一。我们评估了两组中p.R337H的患病率：（1）59名有家族性病史（FH）提示遗传性癌症综合征但无LFS/LFL特征的BC患病女性；（2）815名未因癌症FH进行选择、在45岁及以前或55岁及以后诊断为BC的BC患病女性。在第1组和第2组患者中，分别有2/59（3.4%，CI95%：0.4%-11.7%）和70/815（8.6%，CI95%：6.8%-10.7%）为种系p.R337H携带者。45岁及以前诊断为BC的女性中p.R337H的患病率（12.1%，CI95%：9.1%-15.8%）高于55岁及以后诊断为BC的女性（5.1%，CI95%：3.2%-7.7%），p<0.001。在所有分析的携带者中均检测到巴西奠基者p.R337H单倍型。这些结果表明，除了最近证明的对儿童ACC风险的影响外，p.R337H的遗传可能对巴西BC的高发病率有显著贡献。
