PDF(Pubmed)
Abstract：
UNASSIGNED: There is a significant lack of epidemiological data on hereditary cancer in Northeast Brazil. This is the largest study on the prevalence and mutational spectrum of cancer predisposition genes conducted in this region and the first in the State of Ceará.
UNASSIGNED: Patients ≥18 years of age that were referred to CHANCE (Grupo de Câncer Hereditário do Ceará) from March 2014 to December 2020 with testing criteria for breast cancer susceptibility genes according to NCCN v.1.2021 were eligible to participate. The inclusion of patients was limited to one individual per family and to those born in the State of Ceará. All patients underwent a hereditary cancer panel testing with at least 30 genes.
UNASSIGNED: A total of 355 patients were included, and 97 (27.3%) carried a P/LP germline variant in 18 different genes. Among the 97 P/LP carriers, BRCA1 (31, 31.9%) and BRCA2 (25, 25.7%) were the most frequently mutated genes, followed by PALB2 (10, 10.3%), CHEK2 (7, 7.2%) and ATM (4, 4.1%). A small number of recurrent variants (detected in three or more individuals) in BRCA1, BRCA2, CHEK2 and ATM represented the majority of the P/LP variants described in this cohort.
UNASSIGNED: In this cohort, the prevalence of L/PL was high, particularly involving the BRCA1, BRCA2, PALB2, CHEK2 and ATM genes and, to a lesser extent than expected, the TP53 gene. A high frequency of recurrent variants was also observed, for which further and larger analyses should clarify the presence of any possible founder effect. Characterizing the mutational profile of cancer predisposition genes in diverse populations may contribute to cancer prevention and therapeutic management.
UNASSIGNED: Patients ≥18 years of age that were referred to CHANCE (Grupo de Câncer Hereditário do Ceará) from March 2014 to December 2020 with testing criteria for breast cancer susceptibility genes according to NCCN v.1.2021 were eligible to participate. The inclusion of patients was limited to one individual per family and to those born in the State of Ceará. All patients underwent a hereditary cancer panel testing with at least 30 genes.
UNASSIGNED: A total of 355 patients were included, and 97 (27.3%) carried a P/LP germline variant in 18 different genes. Among the 97 P/LP carriers, BRCA1 (31, 31.9%) and BRCA2 (25, 25.7%) were the most frequently mutated genes, followed by PALB2 (10, 10.3%), CHEK2 (7, 7.2%) and ATM (4, 4.1%). A small number of recurrent variants (detected in three or more individuals) in BRCA1, BRCA2, CHEK2 and ATM represented the majority of the P/LP variants described in this cohort.
UNASSIGNED: In this cohort, the prevalence of L/PL was high, particularly involving the BRCA1, BRCA2, PALB2, CHEK2 and ATM genes and, to a lesser extent than expected, the TP53 gene. A high frequency of recurrent variants was also observed, for which further and larger analyses should clarify the presence of any possible founder effect. Characterizing the mutational profile of cancer predisposition genes in diverse populations may contribute to cancer prevention and therapeutic management.
摘要：
■巴西东北部严重缺乏遗传性癌症的流行病学数据。这是在该地区进行的关于癌症易感性基因的流行和突变谱的最大研究，也是在塞阿拉州进行的首次研究。
■从2014年3月至2020年12月转诊至CHANCE（GrupodeCáncerHereditáriodoCeara）的年龄≥18岁的患者，根据NCCNv.1.2021有资格参加。患者的纳入仅限于每个家庭一名，也仅限于在塞阿拉州出生的患者。所有患者都接受了至少30个基因的遗传性癌症小组测试。
■共纳入355名患者，97（27.3％）在18个不同基因中携带P/LP种系变异。在97个P/LP运营商中，BRCA1(31,31.9%)和BRCA2(25,25.7%)是最常见的突变基因,其次是PALB2（10，10.3％），CHEK2（7，7.2%）和ATM（4，4.1%）。BRCA1、BRCA2、CHEK2和ATM中的少量复发变体(在三个或更多个体中检测到)代表了该队列中描述的大多数P/LP变体。
■在此队列中，L/PL的患病率很高，特别涉及BRCA1，BRCA2，PALB2，CHEK2和ATM基因，程度低于预期，TP53基因。也观察到高频率的复发变异，为此，进一步和更大的分析应该澄清任何可能的创始人效应的存在。表征不同人群中癌症易感性基因的突变谱可能有助于癌症预防和治疗管理。
■从2014年3月至2020年12月转诊至CHANCE（GrupodeCáncerHereditáriodoCeara）的年龄≥18岁的患者，根据NCCNv.1.2021有资格参加。患者的纳入仅限于每个家庭一名，也仅限于在塞阿拉州出生的患者。所有患者都接受了至少30个基因的遗传性癌症小组测试。
■共纳入355名患者，97（27.3％）在18个不同基因中携带P/LP种系变异。在97个P/LP运营商中，BRCA1(31,31.9%)和BRCA2(25,25.7%)是最常见的突变基因,其次是PALB2（10，10.3％），CHEK2（7，7.2%）和ATM（4，4.1%）。BRCA1、BRCA2、CHEK2和ATM中的少量复发变体(在三个或更多个体中检测到)代表了该队列中描述的大多数P/LP变体。
■在此队列中，L/PL的患病率很高，特别涉及BRCA1，BRCA2，PALB2，CHEK2和ATM基因，程度低于预期，TP53基因。也观察到高频率的复发变异，为此，进一步和更大的分析应该澄清任何可能的创始人效应的存在。表征不同人群中癌症易感性基因的突变谱可能有助于癌症预防和治疗管理。
