Data from: Screening familial risk for hereditary breast and ovarian cancer

Background: Most patients with pathogenic or likely pathogenic (P/LP)
variants for breast cancer have not undergone genetic testing. Our primary
objective was to identify patients meeting family history criteria for
genetic testing in the electronic health record (EHR). Methods: This study
included a cross-sectional analysis with an observation date of February
1, 2024. Participants included patients aged 18 to 79 years enrolled in
Renown Health, a large health system in Northern Nevada. Genotype was
known for 38,003 patients enrolled in Healthy Nevada Project (HNP), a
population genomics study. The primary exposure in this study was an EHR
indicating that a patient is positive for criteria according to the
Seven-Question Family History Questionnaire (hereafter, FHS7 positive)
assessing familial risk for hereditary breast and ovarian cancer
(HBOC). The primary outcomes were the presence of P/LP variants
in the ATM, BRCA1, BRCA2, CHEK2,
or PALB2 genes. Results:  Among 835,727 patients, 29,913
(3.6%) were FHS7 positive. Among those who were FHS7 positive, 24,535
(82.0%) had no evidence of prior genetic testing for HBOC in their EHR.
Being FHS7 positive was associated with increased prevalence of P/LP
variants in BRCA1/BRCA2 (odds ratio [OR], 3.34; 95% CI,
2.48-4.47), CHEK2 (OR, 1.62; 95% CI, 1.05-2.43),
and PALB2 (OR, 2.84; 95% CI, 1.23-6.16) among HNP female
individuals, and in BRCA1/BRCA2 (OR, 3.35; 95% CI, 1.93-5.56)
among HNP male individuals. Among 1,527 HNP survey respondents, 352 of 383
EHR-FHS7 positive patients (91.9%) were survey-FHS7 positive, but only 352
of 883 survey-FHS7 positive patients (39.9%) were EHR-FHS7
positive.  Conclusions and Relevance: In this
cross-sectional study, EHR-derived FHS7 identified thousands of patients
with familial risk for breast cancer, indicating a substantial gap in
genetic testing.  Data description:  Data used to create
Tables 1, 3, and 4 of the manuscript are provided as
comma-separated-values files. Data used to create Table 2 and to
train the cause-specific hazard models are are subject to HIPAA and other
privacy and compliance restrictions. Requests for these and other data may
be addressed to Joe Grzymski (at [e-mail]) or Craig Kugler
(at [e-mail]). These data (and other sensitive data) are
available to qualified researchers upon reasonable request and with
permission from the Center for Genomic Medicine. The HNP encourages
collaboration with scientific researchers on an individual basis. Examples
of restrictions that will be considered in requests to data access include
but are not limited to:  1. Whether the request comes
from an academic institution in good standing that will collaborate with
our team toprotect the privacy of the participants and the security of the
data requested. 2. Type and amount of data requested. 3.
Feasibility of the research suggested. 4. Amount of resource allocation to
support the collaboration

研究背景：大多数携带乳腺癌致病性或可能致病性（P/LP）变异的患者未接受过基因检测。本研究的首要目标是在电子健康档案（Electronic Health Record, EHR）中识别符合基因检测家族史标准的患者。
研究方法：本研究为横断面分析，观察日期设定为2024年2月1日。研究对象为内华达州北部大型医疗系统Renown Health注册的18至79岁患者。内华达健康项目（Healthy Nevada Project, HNP）是一项人群基因组学研究，其纳入的38003名患者的基因型信息均已明确。本研究的主要暴露因素为电子健康档案显示患者符合七项问题家族史问卷（Seven-Question Family History Questionnaire，符合该问卷标准者记为FHS7阳性）的评估标准，该问卷用于评估遗传性乳腺癌和卵巢癌（hereditary breast and ovarian cancer, HBOC）的家族患病风险。本研究的主要结局为患者存在ATM、BRCA1、BRCA2、CHEK2或PALB2基因的P/LP变异。
研究结果：在835727名患者中，29913名（3.6%）为FHS7阳性。其中，24535名（82.0%）患者的电子健康档案中无既往接受HBOC基因检测的记录。在HNP的女性受试者中，FHS7阳性与BRCA1/BRCA2、CHEK2及PALB2基因的P/LP变异患病率升高显著相关（比值比[OR]分别为3.34、1.62、2.84，95%置信区间[CI]依次为2.48~4.47、1.05~2.43、1.23~6.16）；在HNP的男性受试者中，FHS7阳性与BRCA1/BRCA2基因的P/LP变异患病率升高显著相关（OR=3.35，95%CI：1.93~5.56）。在1527名HNP调查受访者中，383名电子健康档案-FHS7阳性患者中有352名（91.9%）为调查-FHS7阳性；但883名调查-FHS7阳性患者中仅39.9%（352名）为电子健康档案-FHS7阳性。
研究结论与意义：本横断面研究显示，通过电子健康档案提取的FHS7可识别出数千名存在乳腺癌家族患病风险的患者，这表明当前基因检测存在显著的缺口。
数据说明：本研究手稿中表1、表3及表4所用数据以逗号分隔值（comma-separated values, CSV）文件形式提供。用于制作表2及训练病因特异性风险模型的数据受《健康保险流通与责任法案》（Health Insurance Portability and Accountability Act, HIPAA）及其他隐私与合规性约束。如需获取上述或其他数据，可联系Joe Grzymski（邮箱：[e-mail]）或Craig Kugler（邮箱：[e-mail]）。上述数据（及其他敏感数据）仅可在提出合理申请并获得基因组医学中心许可后，向符合资质的研究人员开放。HNP鼓励与科研人员开展个体化合作。数据访问申请需考量的限制情形包括但不限于：1. 申请方是否为信誉良好的学术机构，且将与本团队合作保护受试者隐私及所申请数据的安全；2. 申请获取的数据类型与数量；3. 所提议研究的可行性；4. 支持本合作所需的资源投入量。