Figlioli Gisella, De Nicolo Arcangela, Catucci Irene, Manoukian Siranoush, Peissel Bernard, Azzollini Jacopo, Beltrami Benedetta, Bonanni Bernardo, Calvello Mariarosaria, Bondavalli Davide, Pasini Barbara, Vignolo Lutati Francesca, Ogliara Paola, Zuradelli Monica, Pensotti Valeria, De Vecchi Giovanna, Volorio Sara, Verderio Paolo, Pizzamiglio Sara, Matullo Giuseppe, Aneli Serena, Birolo Giovanni, Zanardi Federica, Tondini Carlo, Zambelli Alberto, Livraghi Luca, Franchi Michela, Radice Paolo, Peterlongo Paolo
Genome Diagnostics Program, IFOM, FIRC Institute for Molecular Oncology, 20139 Milan, Italy.
Cancer Genomics Program, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy.
Cancers (Basel). 2021 Jan 30;13(3):532. doi: 10.3390/cancers13030532.
Germline pathogenic variants (PVs) in the or genes cause high breast cancer risk. Recurrent or founder PVs have been described worldwide including some in the Bergamo province in Northern Italy. The aim of this study was to compare the PV spectra of the Bergamo and of the general Italian populations. We retrospectively identified at five Italian centers 1019 PVs carrier individuals affected with breast cancer and representative of the heterogeneous national population. Each individual was assigned to the Bergamo or non-Bergamo cohort based on self-reported birthplace. Our data indicate that the Bergamo PV spectrum shows less heterogeneity with fewer different variants and an average higher frequency compared to that of the rest of Italy. Consistently, four PVs explained about 60% of all carriers. The majority of the Bergamo PVs originated locally with only two PVs clearly imported. The Bergamo PV spectrum appears to be private. Hence, the Bergamo population would be ideal to study the disease risk associated with local PVs in breast cancer and other disease-causing genes. Finally, our data suggest that the Bergamo population is a genetic isolate and further analyses are warranted to prove this notion.
BRCA1或BRCA2基因中的种系致病性变异（PVs）会导致乳腺癌风险升高。全世界都有复发性或奠基者PVs的报道，包括意大利北部贝加莫省的一些病例。本研究的目的是比较贝加莫人群和意大利普通人群的PV谱。我们在意大利的五个中心进行回顾性研究，确定了1019名携带PVs且患有乳腺癌的个体，这些个体代表了异质性的全国人群。根据自我报告的出生地，将每个个体分配到贝加莫队列或非贝加莫队列。我们的数据表明，与意大利其他地区相比，贝加莫的PV谱显示出较低的异质性，不同变异较少，平均频率较高。一致的是，四种PVs解释了所有携带者的约60%。贝加莫的大多数PVs起源于当地，只有两种PVs明显是外来的。贝加莫的PV谱似乎是独特的。因此，贝加莫人群将是研究乳腺癌及其他致病基因中与当地PVs相关疾病风险的理想人群。最后，我们的数据表明贝加莫人群是一个遗传隔离群体，有必要进行进一步分析来证实这一观点。
