Germline Mutational Profile Of Chinese Patients Under 70 Years Old With Colorectal Cancer

Background Inherited susceptibility accounts for nearly one-third of colorectal cancer (CRC) predispositions and has an 80%-100% lifetime risk of this disease. However, there are few data about germline mutations of hereditary CRC-related genes in Chinese patients with CRC. This study aimed to assess the prevalence of gene mutations related to cancer susceptibility among Chinese patients with CRC, differences between Chinese and Western patients, and the phenotype-genotype correlation. Methods We retrospectively collected tumor samples from 526 patients with CRC under 70 years old who underwent hereditary CRC genetic testing. A series of bioinformatic analyses, as well as statistical comparisons, were performed. Results We found that 77 patients (14.6%) harbored functional variants of the 12 genes. The mutation frequencies of the top 5 mutated genes were 6.5% for MutL homolog 1 (MLH1), 5.1% for MutS homolog 2 (MSH2), 1.0% forMSH6, 0.8% forPMS1homolog 2 (PMS2), and 0.8% for APC regulator of the WNT signaling pathway (APC). Our data showed much higher rates of mutations ofMSH6andPMS2genes among all mismatch repair (MMR) genes as compared with those in Western populations. Mutations inMLH1,MSH2, andMSH6were found to be mutually exclusive. Patients withMLH1orMSH2mutations had higher frequencies of personal history of cancer (MLH1: 20.6% vs. 8.7%;MSH2: 25.9% vs. 8.6%) and family history of cancer than those without these mutations (MLH1: 73.5% vs. 48.4%;MSH2: 70.4% vs. 48.9%), and the lesions were more prone to occur on the right side of the colon than on the left side (MLH1: 73.5% vs. 29.3%;MSH2: 56.0% vs. 31.0%). The proportion of stage I/II disease was higher in patients withMLH1mutations than in those withoutMLH1mutations (70.6% vs. 50.7%), and the rate of polyps was higher in patients withAPCmutations than in those with wild-typeAPC(75.0% vs. 17.4%). Conclusion These results provide a full-scale landscape of hereditary susceptibility over 12 related genes in CRC patients and suggest that a comprehensive multi-gene panel testing for hereditary CRC predisposition could be a helpful analysis in clinical practice.