APC I1307K和临床管理:来自英国生物银行对德系和非德系白人结直肠癌和其他癌症风险关联分析的见解

IF 3.7 2区 医学 Q2 GENETICS & HEREDITY
Sophie Allen, Charlie F Rowlands, Andrew Latchford, Clare Turnbull, Laura Valle
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引用次数: 0

摘要

背景:APC c.3920T>A;p.i ile1307lys (I1307K)在德系犹太人(AJ)中普遍存在,与结直肠癌(CRC)风险适度增加有关。I1307K杂合子的临床建议因国家和专家组的不同而不同,反映了人群频率的差异、适度的风险估计和非aj个体的有限数据。方法:我们分析了英国生物银行(UK Biobank)数据,包括466315人(8944人患有结直肠癌),使用基因组分析对AJ和非AJ祖先进行分类。结果:I1307K在7.1%的AJ白人和0.08%的非AJ白人中被检出。在AJ (OR: 0.71; 95% CI: 0.17至2.95)或非AJ白人(OR: 1.05; 95% CI: 0.50至2.22)中未观察到与CRC的显著关联。先前建立的AJ个体的OR为1.7-1.8,在我们的95% CI范围内,表明由于CRC病例有限,结果不足。在其他癌症中没有发现明显的关联。在非aj人群中进行的无偏倚、充分有力的CRC病例对照研究需要比现有资源大得多的队列才能进行可行性分析。结论:I1307K的临床可操作性应优先考虑基于整体CRC风险和家族依赖性变异检出率的风险分层。然而,一旦确定携带者,管理策略不必因祖先而异,因为I1307K的生物学影响应该在人群中是一致的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
APC I1307K and clinical management: insights from UK Biobank association analysis of colorectal and other cancer risks in Ashkenazi and non-Ashkenazi whites.

Background: APC c.3920T>A; p.Ile1307Lys (I1307K), prevalent in individuals of Ashkenazi Jewish (AJ) origin, has been associated with a modestly increased colorectal cancer (CRC) risk. Clinical recommendations for I1307K heterozygotes vary across countries and expert groups, reflecting differences in population frequencies, modest risk estimates and limited data in non-AJ individuals.

Methods: We analysed UK Biobank data comprising 466 315 individuals (8944 with CRC), using genomic analysis to classify AJ and non-AJ ancestries.

Results: I1307K was identified in 7.1% of AJ and 0.08% of non-AJ white participants. No significant association with CRC was observed in AJ (OR: 0.71; 95% CI: 0.17 to 2.95) or non-AJ white individuals (OR: 1.05; 95% CI: 0.50 to 2.22). The previously established OR of 1.7-1.8 for AJ individuals lies within our 95% CI, indicating underpowered results due to limited CRC cases. No significant associations were detected for other cancers. Unbiased, adequately powered CRC case-control studies in non-AJ populations would require cohorts far larger than current resources for feasible analysis.

Conclusion: Clinical actionability of I1307K should prioritise risk stratification based on overall CRC risk and ancestry-dependent variant detection rates. However, management strategies need not differ by ancestry once a carrier is identified, as the biological impact of I1307K should be consistent across populations.

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来源期刊
Journal of Medical Genetics
Journal of Medical Genetics 医学-遗传学
CiteScore
7.60
自引率
2.50%
发文量
92
审稿时长
4-8 weeks
期刊介绍: Journal of Medical Genetics is a leading international peer-reviewed journal covering original research in human genetics, including reviews of and opinion on the latest developments. Articles cover the molecular basis of human disease including germline cancer genetics, clinical manifestations of genetic disorders, applications of molecular genetics to medical practice and the systematic evaluation of such applications worldwide.
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