Abstract: Background and purpose: It is suggested that MUTYH mutation is closed to high colorectal cancer risk, but it is not clear that the relationship between MUTYH mutation and susceptibility to familiar breast carcinoma. The study was to investigate the significance of MUTYH c.892-2A>G splicing mutation in familial breast cancer. Methods: The mutations of MUTYH，BRCA1 and BRCA2 genes were tested by the next generation sequencing (NGS) method in total of 224 participants， from 95 families with breast cancer patients (containing breast cancer patients and their relatives), and then comparisons were carried out between them. The mutations detected by NGS were verified by Sanger sequencing. Results: Seven participants from 4 families had a MUTYH c.892-2A>G splicing mutation, with a mutation rate of 3.1% (7/224), of which only one proband carried with this mutation. In 224 participants, only one proband carried with BRCA1 mutation. While 9 participants from 5 families had BRCA2 mutations, and their mutation rate was 4% (9/224). Further the BRCA2 mutation site detected in the proband of every family was not the same. There were no significant differences between the number of MUTYH c.892-2A>G mutation and BRCA2 mutation or between the number of MUTYH c.892-2A>G mutation and BRCA 1 mutation. And there was no case which existed MUTYH and BRCAs gene co-mutations. Conclusion: Although its high mutation rate happens in the high-risk healthy population with a history of breast cancer, MUTYH c.892-2A>G is likely to be a low penetrance gene mutation of susceptibility to breast cancer.

Key words: MUTYH, Familial breast cancer, BRCA1, BRCA2