Comparisons of screening strategies for identifying Lynch syndrome among patients with MLH1-deficient colorectal cancer

doi:10.1038/s41431-020-0687-8

	Comparisons of screening strategies for identifying Lynch syndrome among patients with MLH1-deficient colorectal cancer
	Xiao, Binyi 2,3,4; Luo, Jun 5,6,7; Xie, E.8; Kong, Lingheng 2,3,4; Tang, Jinghua 2,3,4; Liu, Dingxin 2,3,4; Mao, Linlin 1; Sui, Qiaoqi 2,3,4; Li, Weirong 2,3,4; Hong, Zhigang 2,3,4
刊名	EUROPEAN JOURNAL OF HUMAN GENETICS
	2020-07-13
ISSN号	1018-4813
DOI	10.1038/s41431-020-0687-8
通讯作者	Pan, Zhizhong(panzhzh@sysucc.org.cn) ; Jiang, Wu(jiangwu@sysucc.org.cn) ; Ding, Pei-Rong(dingpr@sysucc.org.cn)
英文摘要	BRAFandMLH1promoter methylation testings have been proven effective prescreens for Lynch Syndrome. We aimed to compare different screening strategies for Lynch Syndrome in patients with MLH1(-) CRC. Patients with MLH1(-) CRC who had been tested forBRAFmutation and germline variants of DNA mismatch repair genes were included. We compared the sensitivities and specificities for identifying Lynch Syndrome and the cost-effectiveness of four screening approaches that used the following tests as prescreens:BRAFtesting,MLH1methylation testing,MLH1methylation &BRAFtesting, andMLH1methylation testing & Revised Bethesda Criteria. Of 109 patients included, 23 (21.1%) were Lynch Syndrome patients.BRAFmutation andMLH1methylation occurred in 6 (5.5%) and 40 (36.7%) patients, respectively. The sensitivity for identifying Lynch syndrome ofBRAFtesting was 100%, but the specificity was only 7%.MLH1methylation testing had a lower sensitivity thanBRAFtesting (97.5% vs 100%), but had a markedly higher specificity (45.3% vs 7%). The combination of the two testings had a slightly higher specificity thanMLH1methylation testing alone (47.7% vs 45.3%). TheMLH1methylation testing approach had a 10% lower cost of identifying MLH1(-) Lynch syndrome carriers per case than universal genetic testing, but it missed 4.5% of patients.BRAFandMLH1promoter methylation testings as prescreens for Lynch syndrome are less effective in Chinese patients with MLH1(-) CRC than in their Western counterparts. Universal genetic testing could be considered an up-front option for this population.
资助项目	National Natural Science Foundation of China[81871971] ; Science and Technology Planning Project of Guangzhou City of China[201803010117] ; Science and Technology Program Project of Guangzhou[201802020030]
WOS关键词	MLH1 METHYLATION ; BRAF ; MUTATIONS ; MANAGEMENT ; GUIDELINE ; SOCIETY
WOS研究方向	Biochemistry & Molecular Biology ; Genetics & Heredity
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000548249800003
资助机构	National Natural Science Foundation of China ; Science and Technology Planning Project of Guangzhou City of China ; Science and Technology Program Project of Guangzhou
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/102965]
专题	中国科学院合肥物质科学研究院
通讯作者	Pan, Zhizhong; Jiang, Wu; Ding, Pei-Rong
作者单位	1.Guangzhou Kingmed Diagnost Grp Co Ltd, Clin Genome Ctr, KingMed Ctr Clin Lab Co Ltd, Guangzhou, Peoples R China 2.Sun Yat Sen Univ, Canc Ctr, Guangzhou 510060, Peoples R China 3.State Key Lab Oncol South China, Guangzhou 510060, Peoples R China 4.Collaborat Innovat Ctr Canc Med, Guangzhou 510060, Peoples R China 5.Chinese Acad Sci, Inst Canc & Basic Med ICBM, Hangzhou, Zhejiang, Peoples R China 6.Univ Chinese Acad Sci, Canc Hosp, Hangzhou, Zhejiang, Peoples R China 7.Zhejiang Canc Hosp, Hangzhou, Zhejiang, Peoples R China 8.Sun Yat Sen Univ, Affiliated Shantou Hosp, Dept Gen Surg, Guangzhou 515000, Guangdong, Peoples R China
推荐引用方式 GB/T 7714	Xiao, Binyi,Luo, Jun,Xie, E.,et al. Comparisons of screening strategies for identifying Lynch syndrome among patients with MLH1-deficient colorectal cancer[J]. EUROPEAN JOURNAL OF HUMAN GENETICS,2020.
APA	Xiao, Binyi.,Luo, Jun.,Xie, E..,Kong, Lingheng.,Tang, Jinghua.,...&Ding, Pei-Rong.(2020).Comparisons of screening strategies for identifying Lynch syndrome among patients with MLH1-deficient colorectal cancer.EUROPEAN JOURNAL OF HUMAN GENETICS.
MLA	Xiao, Binyi,et al."Comparisons of screening strategies for identifying Lynch syndrome among patients with MLH1-deficient colorectal cancer".EUROPEAN JOURNAL OF HUMAN GENETICS (2020).