@article{203b971965bf4c7bb996b8613c956ce5,
title = "Universal screening for Lynch syndrome in a large consecutive cohort of Chinese colorectal cancer patients: High prevalence and unique molecular features",
abstract = " The prevalence of Lynch syndrome (LS) varies significantly in different populations, suggesting that ethnic features might play an important role. We enrolled 3330 consecutive Chinese patients who had surgical resection for newly diagnosed colorectal cancer. Universal screening for LS was implemented, including immunohistochemistry for mismatch repair (MMR) proteins, BRAF V600E mutation test and germline sequencing. Among the 3250 eligible patients, MMR protein deficiency (dMMR) was detected in 330 (10.2%) patients. Ninety-three patients (2.9%) were diagnosed with LS. Nine (9.7%) patients with LS fulfilled Amsterdam criteria II and 76 (81.7%) met the revised Bethesda guidelines. Only 15 (9.7%) patients with absence of MLH1 on IHC had BRAF V600E mutation. One third (33/99) of the MMR gene mutations have not been reported previously. The age of onset indicates risk of LS in patients with dMMR tumors. For patients older than 65 years, only 2 patients (5.7%) fulfilling revised Bethesda guidelines were diagnosed with LS. Selective sequencing of all cases with dMMR diagnosed at or below age 65 years and only of those dMMR cases older than 65 years who fulfill revised Bethesda guidelines results in 8.2% fewer cases requiring germline testing without missing any LS diagnoses. While the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of constitutional mutations and frequency of BRAF V600E mutation is different. Patients older than 65 years who do not meet the revised Bethesda guidelines have a low risk of LS, suggesting germline sequencing might not be necessary in this population.",
keywords = "Lynch syndrome, colorectal cancer, ethnic diversity, universal screening",
author = "{Written on behalf of AME Colorectal Cancer Cooperative Group} and Wu Jiang and Cai, {Mu Yan} and Li, {Shi Yong} and Bei, {Jin Xin} and Fang Wang and Heather Hampel and Ling, {Yi Hong} and Frayling, {Ian M.} and Sinicrope, {Frank A.} and Rodriguez-Bigas, {Miguel A.} and Dignam, {James J.} and Kerr, {David J.} and Rafael Rosell and Mao Mao and Li, {Ji Bin} and Guo, {Yun Miao} and Wu, {Xiao Yan} and Kong, {Ling Heng} and Tang, {Jing Hua} and Wu, {Xiao Dan} and Li, {Chao Feng} and Chen, {Jie Rong} and Ou, {Qing Jian} and Ye, {Ming Zhi} and Guo, {Feng Ming} and Peng Han and Wang, {Qi Wei} and Wan, {De Sen} and Li Li and Xu, {Rui Hua} and Pan, {Zhi Zhong} and Ding, {Pei Rong}",
note = "Funding Information: Key words: colorectal cancer, Lynch syndrome, universal screening, ethnic diversity Abbreviations: CNV: copy number variations; CRC: colorectal cancer; dMMR: MMR protein deficiency; IHC: immunohistochemical; InSiGHT: International Society of Gastrointestinal Hereditary Tumors; LOVD: Leiden Open Variation Database; LS: Lynch syndrome; MMR: mismatch repair; PCR: polymerase chain reaction; VUS: variants of uncertain significance Additional Supporting Information may be found in the online version of this article. Conflict of interest: Ms Hampel discloses a scientific advising role with Invitae and Genome Medical, research collaborations with Ambry, Invite, and Myriad Genetics Inc, and stock in Genome medical. No other conflicts are reported. †W.J., M.C., S.L., and J.B. contributed equally to this work Grant sponsor: National Key R&D Program of China; Grant number: 2017YFC0908200; Grant sponsor: Health & Medical collaborative innovation project of Guangzhou city; Grant number: 201604020003; Grant sponsor: the Fundamental Research Funds for young teachers in basic research of Sun Yat-sen University; Grant number: 16kyzd01; Grant sponsor: the Pearl River Nova Program of Guangzhou; Grant number: 201506010065; Grant sponsor: the Science and Technology Project Foundation of Guangdong Province; Grant number: 2015B020232008; Grant sponsor: the Science and Technology Project of Guangzhou; Grant numbers: 201400000001-4 and 201400000004-5 DOI: 10.1002/ijc.32044 History: Received 26 Jun 2018; Accepted 4 Oct 2018; Online 6 Dec 2018 Correspondence to: Prof. Pei-Rong Ding, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People{\textquoteright}s Republic of China, E-mail: dingpr@sysucc.org.cn; Tel.: +86 20 87343920; or Prof. Rui-Hua Xu, Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People{\textquoteright}s Republic of China, E-mail: xurh@sysucc.org.cn; or Prof. Zhi-Zhong Pan, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People{\textquoteright}s Republic of China, E-mail: panzhzh@sysucc.org.cn Publisher Copyright: {\textcopyright} 2018 UICC",
year = "2019",
month = may,
day = "1",
doi = "10.1002/ijc.32044",
language = "English (US)",
volume = "144",
pages = "2161--2168",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "9",
}