Pathogenic Variants in Less Familiar Cancer Susceptibility Genes: What Happens After Genetic Testing?
Pathogenic Variants in Less Familiar Cancer Susceptibility Genes: What Happens After Genetic Testing?
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DOI：
10.1200/po.18.00167
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发表时间：
2018-11-08
影响因子：
4.6
通讯作者：
Kurian, Allison W.
中科院分区：
文献类型：
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作者：
Hall, Evan T.;Parikh, Divya;Kurian, Allison W.
随着基因检测的扩展，越来越多的患者被发现携带大多数临床医生不太熟悉的癌症易感基因的致病性变体，特别是导致遗传性乳腺卵巢癌综合征（BRCA 1和BRCA 2）和Lynch综合征的基因。方法2013年1月至2015年7月在斯坦福大学癌症遗传学诊所接受咨询和测试的所有成年患者，在非BRCA 1/2，非Lynch综合征基因中存在致病性变异，被邀请参加关于遵守降低风险建议的电话采访，结果142名符合条件的患者中有57名（40%）成功联系，所有57名患者均参与;中位随访时间为677天（范围：247至1，401天）。大多数患者（82%; 95% CI，70%-90%）回忆起建议进行风险降低干预（筛查、药物治疗或手术），大多数患者（85%; 95% CI，72%-93%）遵守了建议。几乎所有患者（91%; 95% CI，81%至97%）与亲属共享结果，大多数患者（78%; 95% CI，64%至88%）报告随后对亲属进行了检测。在随访期间，9%的患者（95%CI，3%至19%）开发的第二个癌症，并在14%的患者（95%CI，7%至26%），一级亲属开发的癌症，其中一些被检测到推荐screen.Conclusion患者的致病性变异在一个不太熟悉的癌症易感基因报告高坚持降低风险的干预措施。此外，在57名携带者和随后接受检测的亲属中，经过两年的随访，通过根据致病性变异推荐的干预措施，共检测到3种癌症（1种在先证者中，2种在亲属中）。这些结果表明，遗传咨询和检测不太熟悉的基因中的致病性变异的潜在益处。(C)2018年美国临床肿瘤学会
Purpose As genetic testing expands, patients are increasingly found to carry pathogenic variants in cancer susceptibility genes that are less familiar to most clinicians, specifically genes other than those causing hereditary breast ovarian cancer syndrome (BRCA1 and BRCA2) and Lynch syndrome. Little is known about the subsequent behaviors of such patients in terms of managing cancer risks and informing relatives.Methods All adult patients who were counseled and tested at the Stanford Cancer Genetics Clinic from January 2013 to July 2015 and had a pathogenic variant in a non-BRCA1/2, non-Lynch syndrome gene were invited to participate in a telephone interview about adherence to risk-reducing recommendations, genetic testing by relatives, and new cancer incidence.Results Fifty-seven (40%) of 142 eligible patients were successfully contacted, and all 57 patients participated; median follow-up was 677 days (range, 247 to 1,401 days). Most patients (82%; 95% CI, 70% to 90%) recalled that a risk-reducing intervention (screening, medication, or surgery) was recommended, and most patients (85%; 95% CI, 72% to 93%) adhered to the recommendation. Nearly all patients (91%; 95% CI, 81% to 97%) shared results with relatives, and most patients (78%; 95% CI, 64% to 88%) reported that a relative was subsequently tested. During the follow-up period, 9% of patients (95% CI, 3% to 19%) developed second cancers, and in 14% of patients (95% CI, 7% to 26%), a first-degree relative developed cancer, some of which were detected by recommended screening.Conclusion Patients with a pathogenic variant in a less familiar cancer susceptibility gene report high adherence to risk-reducing interventions. Furthermore, in the 57 carriers and subsequently tested relatives with two years of follow-up, a total of three cancers (one in a proband and two in relatives) were detected through interventions recommended on the basis of the pathogenic variant. These results suggest a potential benefit of genetic counseling and testing for pathogenic variants in less familiar genes. (C) 2018 by American Society of Clinical Oncology