Myriad Women's Health, South San Francisco, California.
Myriad Genetics, Salt Lake City, Utah.
Cancer. 2020 Feb 1;126(3):549-558. doi: 10.1002/cncr.32572. Epub 2019 Nov 4.
Although management guidelines exist for several genes associated with a 2-fold to 5-fold increase in the relative risk for certain cancers, the value of testing for them remains controversial.
De-identified personal and family history data for 654 individuals with pathogenic variants (PVs) in PALB2, ATM, CHEK2, NBN, BRIP1, RAD51C, and/or RAD51D were analyzed for pretest and post-test candidacy for guideline-recommended management of cancer risk. These individuals were invited to complete a survey about provider recommendations and their adherence.
Twenty-four percent of CHEK2, ATM, PALB2, or NBN PV carriers were appropriate for consideration of annual breast magnetic resonance imaging screening before genetic testing, with the remaining 76% appropriate only after testing. No BRIP1, RAD51C, or RAD51D PV carriers were appropriate for consideration of risk-reducing salpingo-oophorectomy before genetic testing; 100% were appropriate only after testing. Seventeen percent of CHEK2 PV carriers were appropriate for earlier and more frequent colonoscopy before genetic testing, with the remaining 83% appropriate only after testing. Provider recommendations for annual breast magnetic resonance imaging, consideration of risk-reducing salpingo-oophorectomy, and earlier and more frequent colonoscopy were reported by 42%, 26%, and 66% of breast, ovarian, and colorectal cancer risk PV carriers, respectively, before genetic testing, versus 82%, 79%, and 81%, respectively, after testing. Nearly all respondents had planned or undertaken provider-recommended management.
Testing for PALB2, ATM, CHEK2, NBN, BRIP1, RAD51C, and RAD51D changed management for those carrying PVs. Provider recommendations were aligned with guidelines, and patients adhered to recommendations, both of which are critical for reducing both long-term cancer morbidity and mortality.
虽然有管理指南针对某些癌症的相对风险增加 2 至 5 倍的几种基因，但对其进行检测的价值仍存在争议。
对 654 名携带 PALB2、ATM、CHEK2、NBN、BRIP1、RAD51C 和/或 RAD51D 致病性变异（PV）的个体的个人和家族史数据进行分析，以确定是否符合指南推荐的癌症风险管理标准。这些个体被邀请完成一份关于提供者建议及其依从性的调查。
在进行基因检测之前，24%的 CHEK2、ATM、PALB2 或 NBN PV 携带者适合考虑每年进行乳房磁共振成像筛查，而其余 76%的携带者仅在检测后才适合考虑。BRIP1、RAD51C 或 RAD51D 无 PV 携带者适合考虑在基因检测前进行降低风险的输卵管卵巢切除术；100%的人仅在检测后才适合考虑。在进行基因检测之前，17%的 CHEK2 PV 携带者适合更早、更频繁地进行结肠镜检查，而其余 83%的携带者仅在检测后才适合。在进行基因检测之前，分别有 42%、26%和 66%的乳腺癌、卵巢癌和结直肠癌风险 PV 携带者报告了提供者建议进行年度乳房磁共振成像检查、考虑降低风险的输卵管卵巢切除术和更早、更频繁的结肠镜检查，而在进行基因检测之后，这一比例分别为 82%、79%和 81%。几乎所有的受访者都计划或接受了提供者推荐的管理。
PALB2、ATM、CHEK2、NBN、BRIP1、RAD51C 和 RAD51D 的检测改变了携带 PV 个体的管理方式。提供者的建议与指南一致，且患者遵循了这些建议，这对于降低长期癌症发病率和死亡率都是至关重要的。
Zotero 插件
