N95: Screening of hereditary CRC at a Chinese cancer center

Peirong Ding1, Wu Jiang1, Zhizhong Pan1, Ruihua Xu2

1 – Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, PR China. 2 – Medical oncology, Sun Yat-Sen University Cancer Center, Guangzhou, PR China.

Background: Prevalence and genotype of hereditary colorectal cancer (CRC) varies significantly in different populations. China has large population but data of hereditary CRC was limited: 376,300 newly diagnosed CRC per year. CRC with unique characteristic in Chinese population: early onset, 10-12 years earlier than the West; site, rectum predominate and more lower locating.

Methods: Universal screening for Lynch syndrome (LS) was performed in patients who had surgical resection for newly diagnosed CRC in SYSUCC from 2011-2015. Germline cancer susceptibility gene mutations was tested in unselected patients with CRC.

Results: 1)  Universal screening for LS in a large consecutive CRC cohort: prevalence of dMMR and LS were 10.2% (330/3250) and 2.9% (93/3191) respectively; only 9.7% (15/154) 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 tumours; 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. 2) Universal germline sequencing for unselected CRC cohort: forty-four (9.9%) of 433 participants carried one or more pathogenic mutations, including 25 (5.6%) with LS; six (1.4%) patients with polyposis syndrome related gene mutations (4 APC and 2 monoallelic MUTYH); fourteen (3.2%) patients carried pathogenic mutations not traditionally associated with hereditary CRC (three BRCA1/2, two ATM, two CHEK2, two BLM, two CDH1, one TP53, one NBN, and one RAD51C).

Conclusions: Ethnic diversity might play an important role in heredtary CRC. The Chinese CRC patients has relatively high prevalence of LS and unique molecular features. Patients older than 65y who do not meet the revised Bethesda guidelines have a low risk of LS, suggesting germline sequencing might not be necessary in this population. Universal germline sequencing could detected more patients with cancer susceptibility gene mutations, especially those untraditional CRC genes.