Hospital Universitario General de Medellín, Medellín, Colombia.
Department of Oncology, Hospital Sírio-Libanês, Brasília, Distrito Federal, Brazil.
JCO Glob Oncol. 2022 Jul;8:e2200104. doi: 10.1200/GO.22.00104.
To report on pathogenic germline variants detected among individuals undergoing genetic testing for hereditary breast and/or ovarian cancer (HBOC) from Latin America and compare them with self-reported Hispanic individuals from the United States.
In this cross-sectional study, unrelated individuals with a personal/family history suggestive of HBOC who received clinician-ordered germline multigene sequencing were grouped according to the location of the ordering physician: group A, Mexico, Central America, and the Caribbean; group B, South America; and group C, United States with individuals who self-reported Hispanic ethnicity. Relatives who underwent cascade testing were analyzed separately.
Among 24,075 unrelated probands across all regions, most were female (94.9%) and reported a personal history suggestive of HBOC (range, 65.0%-80.6%); the mean age at testing was 49.1 ± 13.1 years. The average number of genes analyzed per patient was highest in group A (A 63 ± 28, B 56 ± 29, and C 40 ± 28). Between 9.1% and 18.7% of patients had pathogenic germline variants in HBOC genes (highest yield in group A), with the majority associated with high HBOC risk. Compared with US Hispanics individuals the overall yield was significantly higher in both Latin American regions (A C = 1.64×10, B C < 2.2×10). Rates of variants of uncertain significance were similar across all three regions (33.7%-42.6%). Cascade testing uptake was low in all regions (A 6.6%, B 4.5%, and C 1.9%).
This study highlights the importance of multigene panel testing in Latin American individuals with newly diagnosed or history of HBOC, who can benefit from medical management changes including targeted therapies, eligibility to clinical trials, risk-reducing surgeries, surveillance and prevention of secondary malignancy, and genetic counseling and subsequent cascade testing of at-risk relatives.
报告在拉丁美洲接受遗传性乳腺癌和/或卵巢癌（HBOC）遗传检测的个体中检测到的致病性种系变异，并将其与美国自我报告的西班牙裔个体进行比较。
在这项横断面研究中，根据开单医生的位置将具有 HBOC 个人/家族史的无关个体分为以下三组：A 组，墨西哥、中美洲和加勒比地区；B 组，南美洲；C 组，美国，且组内个体自我报告为西班牙裔。单独分析接受级联检测的亲属。
在所有地区的 24075 名无关先证者中，大多数为女性（94.9%），报告有个人病史提示 HBOC（范围为 65.0%-80.6%）；检测时的平均年龄为 49.1±13.1 岁。每位患者平均分析的基因数量最高的是 A 组（A 组 63±28，B 组 56±29，C 组 40±28）。9.1%-18.7%的患者存在 HBOC 基因的致病性种系变异（A 组的检出率最高），其中大多数与 HBOC 高风险相关。与美国西班牙裔个体相比，拉丁美洲两个地区的总体检出率均显著更高（A 组与 C 组的比值为 1.64×10，B 组与 C 组的比值 < 2.2×10）。所有三个地区的意义未明变异的检出率相似（33.7%-42.6%）。所有三个地区的级联检测接受率均较低（A 组 6.6%，B 组 4.5%，C 组 1.9%）。
本研究强调了在新诊断或有 HBOC 病史的拉丁美洲个体中进行多基因panel 检测的重要性，这些个体可以从医疗管理改变中获益，包括靶向治疗、有资格参加临床试验、降低风险的手术、监测和预防继发性恶性肿瘤、遗传咨询以及随后对高危亲属的级联检测。
