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Universal screening for Lynch syndrome in a large consecutive cohort of Chinese colorectal cancer patients: High prevalence and unique molecular features
Author(s) -
Jiang Wu,
Cai MuYan,
Li ShiYong,
Bei JinXin,
Wang Fang,
Hampel Heather,
Ling YiHong,
Frayling Ian M.,
Sinicrope Frank A.,
RodriguezBigas Miguel A.,
Dignam James J.,
Kerr David J.,
Rosell Rafael,
Mao Mao,
Li JiBin,
Guo YunMiao,
Wu XiaoYan,
Kong LingHeng,
Tang JingHua,
Wu XiaoDan,
Li ChaoFeng,
Chen JieRong,
Ou QingJian,
Ye MingZhi,
Guo FengMing,
Han Peng,
Wang QiWei,
Wan DeSen,
Li Li,
Xu RuiHua,
Pan ZhiZhong,
Ding PeiRong
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32044
Subject(s) - lynch syndrome , medicine , germline mutation , colorectal cancer , mlh1 , cohort , cancer , germline , oncology , genetic testing , dna mismatch repair , mutation , pediatrics , genetics , gene , biology
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.