Family history assessment significantly enhances delivery of precision medicine in the genomics era.
Family history assessment significantly enhances delivery of precision medicine in the genomics era.
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DOI：
10.1186/s13073-020-00819-1
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发表时间：
2021-01-07
期刊：
影响因子：
12.3
通讯作者：
Tan P
中科院分区：
文献类型：
--
作者：
Bylstra Y;Lim WK;Kam S;Tham KW;Wu RR;Teo JX;Davila S;Kuan JL;Chan SH;Bertin N;Yang CX;Rozen S;Teh BT;Yeo KK;Cook SA;Jamuar SS;Ginsburg GS;Orlando LA;Tan P
家族史传统上是评估健康风险的临床护理的重要组成部分。然而，不断下降的测序成本促使人群筛查项目转向基因组学优先的方法，使得家族史的价值不得而知。我们评估了结合家族史信息进行基因组测序选择的实用性。为了确定家族史与这类人群层面倡议之间的关系，我们分析了1750名没有已知既往疾病的研究参与者的全基因组序列，其中一半人接受了长达四代的综合家族史评估，重点是95个癌症基因。在1750名参与者中，866人(49.5%)拥有高质量的标准化家族史。在这一组中，73名(8.4%)参与者的癌症家族史风险增加(FH风险队列增加)，7名参与者中有1名(n = 10/73)携带临床上可操作的变异，从而推断出6倍于47名平均家族史癌症风险(平均FH风险队列)评估的参与者(n = 17/793)(p = 0.00001)，比52名没有家族病史(FH风险队列)的参与者(n = 17/884)高7倍(p = 0.00001)。当仅评估美国医学遗传学学会(ACMG)二次发现(SF)基因中的25个癌症基因时，这种浓缩进一步明显(高达18倍)。此外，63名参与者(7.3%)在没有明显的临床可操作变异的情况下有更高的家族癌症风险。这些发现表明，收集和分析全面的家族史和基因组数据是相辅相成的，结合起来可以优先考虑个体进行基因组分析。因此，家族史仍然是健康风险评估的关键组成部分，在实施基因组学筛查计划时提供重要的可操作数据。临床试验.gov NCT02791152。追溯登记于2016年5月31日。网上版载有补充材料，可在10.1186/s13073-020-00819-1查阅。
Family history has traditionally been an essential part of clinical care to assess health risks. However, declining sequencing costs have precipitated a shift towards genomics-first approaches in population screening programs rendering the value of family history unknown. We evaluated the utility of incorporating family history information for genomic sequencing selection. To ascertain the relationship between family histories on such population-level initiatives, we analysed whole genome sequences of 1750 research participants with no known pre-existing conditions, of which half received comprehensive family history assessment of up to four generations, focusing on 95 cancer genes. Amongst the 1750 participants, 866 (49.5%) had high-quality standardised family history available. Within this group, 73 (8.4%) participants had an increased family history risk of cancer (increased FH risk cohort) and 1 in 7 participants (n = 10/73) carried a clinically actionable variant inferring a sixfold increase compared with 1 in 47 participants (n = 17/793) assessed at average family history cancer risk (average FH risk cohort) (p = 0.00001) and a sevenfold increase compared to 1 in 52 participants (n = 17/884) where family history was not available (FH not available cohort) (p = 0.00001). The enrichment was further pronounced (up to 18-fold) when assessing only the 25 cancer genes in the American College of Medical Genetics (ACMG) Secondary Findings (SF) genes. Furthermore, 63 (7.3%) participants had an increased family history cancer risk in the absence of an apparent clinically actionable variant. These findings demonstrate that the collection and analysis of comprehensive family history and genomic data are complementary and in combination can prioritise individuals for genomic analysis. Thus, family history remains a critical component of health risk assessment, providing important actionable data when implementing genomics screening programs. ClinicalTrials.gov NCT02791152. Retrospectively registered on May 31, 2016. The online version contains supplementary material available at 10.1186/s13073-020-00819-1.
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