构建用于[具体内容]和测试的“接下来会怎样”队列：描述性分析。（注：原文中“Building the What Comes Next Cohort for and testing”里两个“for”后面的内容缺失）

Building the What Comes Next Cohort for and testing: a descriptive analysis.

作者信息

Dossa Fahima, Metcalfe Kelly, Sutradhar Rinku, Little Tari, Eisen Andrea, Chun Kathy, Meschino Wendy S, Velsher Lea, Ellis Jordan Lerner, Baxter Nancy N

机构信息

Division of General Surgery, Department of Surgery (Dossa), Institute of Health Policy, Management and Evaluation (Dossa, Sutradhar, Baxter), Lawrence S. Bloomberg Faculty of Nursing ( Metcalfe) Division of Biostatistics, Dalla Lana School of Public Health (Sutradhar), Department of Pediatrics (Meschino) and Department of Laboratory Medicine and Pathobiology (Lerner Ellis), University of Toronto; ICES Central (Sutradhar); Department of Surgery (Little), St. Michael's Hospital; Odette Cancer Centre (Eisen), Sunnybrook Health Sciences Centre; Department of Paediatric Laboratory Medicine (Chun), The Hospital for Sick Children; Genetics Program (Meschino, Velsher), North York General Hospital; Lunenfeld-Tanenbaum Research Institute (Lerner Ellis) and Pathology and Laboratory Medicine (Lerner Ellis), Mount Sinai Hospital, Sinai Health System, Toronto, Ont.; Melbourne School of Population and Global Health (Baxter), University of Melbourne, Melbourne, Victoria, Australia.

出版信息

CMAJ Open. 2021 Sep 21;9(3):E874-E885. doi: 10.9778/cmajo.20200228. Print 2021 Jul-Sep.

DOI:10.9778/cmajo.20200228

PMID:34870614

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8741196/

Abstract

BACKGROUND

Our understanding of how testing for and mutations of the and genes affect cancer risk and the use of risk-reduction strategies comes largely from studies of women recruited from specialized genetics clinics. Our aim was to assemble a generalizable cohort of women who underwent testing (the What Comes Next Cohort), irrespective of test result, to enable study of health care utilization and outcomes after testing.

METHODS

This descriptive study included adult women (≥ 18 yr) who met at least 1 of 13 provincial criteria for / testing and who underwent genetic testing at sites in Ontario, Canada, from 2007 to 2016. Most of the women were tested at 1 of 2 main sites, which together capture about 70% of all testing in the province. We collected detailed demographic, genetic testing and family history data through chart review for linkage with data from administrative health databases providing information on cancer history before and after testing. We followed all women to September 2019, evaluating the demographic characteristics of the cohort, indications for testing and test results.

RESULTS

We identified 15 986 women (mean age 52.5 [standard deviation 13.9] yr) who underwent / testing. Of these, 2033 women had positive results, 1175 women had variants of uncertain significance, and 12 778 women had negative results. Positive yields were 41.0% (955/2329) for predictive testing (for familial variants), 10.4% (216/2072) for Ashkenazi Jewish founder testing and 7.4% (862/11 585) for complete gene analysis. Six of the 13 provincial testing criteria had less than 10% positive yield. Among 403 women who tested negative for Ashkenazi Jewish founder mutations and subsequently underwent complete gene analysis, 12 (3.0%) tested positive for alternate pathogenic or likely pathogenic variants in the or gene.

INTERPRETATION

Several provincial eligibility criteria for testing led to positive results in less than 10% of cases. How testing influences women's health care behaviours, particularly those with negative results and those found to carry variants of uncertain significance, is unknown; the What Comes Next Cohort will be instrumental in the study of long-term implications of testing.

摘要

背景

我们对乳腺癌基因1（BRCA1）和乳腺癌基因2（BRCA2）检测及突变如何影响癌症风险以及降低风险策略的应用的理解，很大程度上来自于从专门的遗传学诊所招募的女性的研究。我们的目标是组建一个可推广的接受BRCA检测的女性队列（“后续情况队列”），无论检测结果如何，以便研究检测后的医疗保健利用情况和结果。

方法

这项描述性研究纳入了成年女性（≥18岁），她们符合加拿大安大略省13项BRCA检测省级标准中的至少1项，并于2007年至2016年在加拿大安大略省的一些机构接受了基因检测。大多数女性在2个主要机构中的1个进行检测，这2个机构合计占该省所有BRCA检测的约70%。我们通过病历审查收集了详细的人口统计学、基因检测和家族史数据，以便与行政健康数据库中的数据进行关联，这些数据库提供检测前后癌症病史的信息。我们对所有女性进行随访至2019年9月，评估队列的人口统计学特征、检测指征和检测结果。

结果

我们确定了15986名接受BRCA检测的女性（平均年龄52.5岁[标准差13.9岁]）。其中，2033名女性检测结果为阳性，1175名女性携带意义不明确的变异，12778名女性检测结果为阴性。预测性检测（针对家族性变异）的阳性率为41.0%（955/2329），德系犹太人群奠基者突变检测的阳性率为10.4%（216/2072），完整基因分析的阳性率为7.4%（862/11585）。13项省级检测标准中的6项阳性率低于10%。在403名德系犹太人群奠基者突变检测为阴性且随后接受完整基因分析的女性中，12名（3.0%）在BRCA1或BRCA2基因中检测到其他致病或可能致病的变异呈阳性。