Manchanda Ranjit, Loggenberg Kelly, Sanderson Saskia, Burnell Matthew, Wardle Jane, Gessler Sue, Side Lucy, Balogun Nyala, Desai Rakshit, Kumar Ajith, Dorkins Huw, Wallis Yvonne, Chapman Cyril, Taylor Rohan, Jacobs Chris, Tomlinson Ian, McGuire Alistair, Beller Uziel, Menon Usha, Jacobs Ian
Affiliation of authors: Department of Women's Cancer, EGA Institute for Women's Health, University College London, London, UK (RM, KL, MB, SG, LS, NB, RD, UM, IJ); Department of Gynaecological Oncology, St Bartholomew's Hospital, London, UK (RM); Mount Sinai School of Medicine, New York, NY (SS); Behavioral Sciences Unit, Department of Epidemiology and Public Health, University College London, London, UK (JW); Department of Clinical Genetics, North East Thames Regional Genetics Unit, Great Ormond Street Hospital, London, UK (AK); Department of Clinical Genetics, North West Thames Regional Genetics Unit, Northwick Park Hospital, London, UK (HD); West Midlands Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK (YW); Department of Clinical Genetics, West Midlands Regional Genetics Service, Birmingham Women's NHS Foundation Trust, Birmingham, UK (CC); South West Thames Molecular Genetics Diagnostic Laboratory, St George's Hospital, London, UK (RT); Department of Clinical Genetics, Guy's Hospital, London, UK (CJ); London Research Institute, Cancer Research UK (IT); Department of Health Economics, London School of Economics, London, UK (AM); Department of Gynaecology, Shaare Zedek Medical Center, Jerusalem, Israel (UB); Faculty of Medical and Human Sciences, University of Manchester, Oxford Road, Manchester, UK (IJ).
J Natl Cancer Inst. 2014 Nov 30;107(1):379. doi: 10.1093/jnci/dju379. Print 2015 Jan.
Technological advances raise the possibility of systematic population-based genetic testing for cancer-predisposing mutations, but it is uncertain whether benefits outweigh disadvantages. We directly compared the psychological/quality-of-life consequences of such an approach to family history (FH)-based testing.
In a randomized controlled trial of BRCA1/2 gene-mutation testing in the Ashkenazi Jewish (AJ) population, we compared testing all participants in the population screening (PS) arm with testing those fulfilling standard FH-based clinical criteria (FH arm). Following a targeted community campaign, AJ participants older than 18 years were recruited by self-referral after pretest genetic counseling. The effects of BRCA1/2 genetic testing on acceptability, psychological impact, and quality-of-life measures were assessed by random effects regression analysis. All statistical tests were two-sided.
One thousand, one hundred sixty-eight AJ individuals were counseled, 1042 consented, 1034 were randomly assigned (691 women, 343 men), and 1017 were eligible for analysis. Mean age was 54.3 (SD = 14.66) years. Thirteen BRCA1/2 carriers were identified in the PS arm, nine in the FH arm. Five more carriers were detected among FH-negative FH-arm participants following study completion. There were no statistically significant differences between the FH and PS arms at seven days or three months on measures of anxiety, depression, health anxiety, distress, uncertainty, and quality-of-life. Contrast tests indicated that overall anxiety (P = .0001) and uncertainty (P = .005) associated with genetic testing decreased; positive experience scores increased (P = .0001); quality-of-life and health anxiety did not change with time. Overall, 56% of carriers did not fulfill clinical criteria for genetic testing, and the BRCA1/2 prevalence was 2.45%.
Compared with FH-based testing, population-based genetic testing in Ashkenazi Jews doesn't adversely affect short-term psychological/quality-of-life outcomes and may detect 56% additional BRCA carriers.
技术进步增加了对癌症易感突变进行基于人群的系统基因检测的可能性，但尚不确定其利弊孰多。我们直接比较了这种检测方法与基于家族史（FH）检测的心理/生活质量结果。
在一项针对阿什肯纳兹犹太人（AJ）人群的BRCA1/2基因突变检测的随机对照试验中，我们将人群筛查（PS）组中所有参与者的检测与对符合基于FH的标准临床标准的参与者（FH组）的检测进行了比较。在有针对性的社区宣传活动之后，18岁以上的AJ参与者在接受检测前的遗传咨询后通过自我推荐招募。通过随机效应回归分析评估BRCA1/2基因检测对可接受性、心理影响和生活质量指标的影响。所有统计检验均为双侧检验。
1168名AJ个体接受了咨询，1042人同意，1034人被随机分配（691名女性，343名男性），1017人符合分析条件。平均年龄为54.3（标准差=14.66）岁。在PS组中鉴定出13名BRCA1/2携带者，FH组中有9名。研究完成后，在FH组中FH阴性的参与者中又检测出5名携带者。在焦虑、抑郁、健康焦虑、痛苦、不确定性和生活质量指标方面，FH组和PS组在7天或3个月时没有统计学上的显著差异。对比测试表明与基因检测相关的总体焦虑（P = 0.0001）和不确定性（P = 0.005）降低；积极体验得分增加（P = 0.0001）；生活质量和健康焦虑没有随时间变化。总体而言，56%的携带者不符合基因检测的临床标准，BRCA1/2患病率为2.45%。
与基于FH的检测相比，对阿什肯纳兹犹太人进行基于人群的基因检测不会对短期心理/生活质量结果产生不利影响，并且可能多检测出56%的BRCA携带者。
