Comparison of clinical features between suspected familial colorectal cancer type X and Lynch syndrome in Japanese patients with colorectal cancer: a cross-sectional study conducted by the Japanese Society for Cancer of the Colon and Rectum.

OBJECTIVE The characteristics of familial colorectal cancer type X are poorly defined. Here we aimed to clarify the differences in clinical features between suspected familial colorectal cancer type X and Lynch syndrome in Japanese patients. METHODS We performed germline mutation analyses of mismatch repair genes in 125 patients. Patients who met the Amsterdam Criteria I but lacked mismatch repair gene mutations were diagnosed with suspected familial colorectal cancer type X. RESULTS We identified 69 patients with Lynch syndrome and 25 with suspected familial colorectal cancer type X. The frequencies of gastric and extracolonic Lynch syndrome-associated cancers were lower with suspected familial colorectal cancer type X than with Lynch syndrome. The number of organs with Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. The cumulative incidence of extracolonic Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. We estimated that the median cancer risk in 60-year-old patients with Lynch syndrome was 89, 36 and 24% for colorectal, endometrial and gastric cancers, respectively. Analyses of family members, including probands, revealed that the median age at diagnosis of extracolonic Lynch syndrome-associated cancer was significantly older with suspected familial colorectal cancer type X than with Lynch syndrome. The frequency of extracolonic Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. CONCLUSION A significant difference in extracolonic Lynch syndrome-associated cancer was evident between suspected familial colorectal cancer type X and Lynch syndrome.