Cancers in DNA mismatch repair mutation carriers: results from a hospital based Lynch syndrome registry

Method There were a total of 463 cancers recorded in 239 patients from 150 families enrolled in the Lynch syndrome registry at MD Anderson Cancer Center. Each of these patients had a confirmed germline MMR mutation. Overall there were 218 (47.1%) colorectal and 245 (52.9%) extracolonic cancers. There was no difference in the total number of colorectal and extracolonic cancers in MLH1 mutation carriers (50.3% vs 49.7%) whereas for MSH2 and MLH6 mutation carriers there were more extracolonic than colorectal cancers overall (54.2% vs. 45.8% for MSH2 and 61.9% vs. 38.1% for MSH6). Men had fewer extracolonic cancers than colorectal (44.6% vs. 55.4%), whereas women had more extracolonic cancers than colorectal (58.9% vs. 41.1%). The mean age at diagnosis for extracolonic cancers was older than for colorectal, 48.6 vs. 44.5 years (P=<0.001). There were no significant differences by race between the colorectal and extracolonic cancers in Whites, African Americans and Hispanics. Results The index cancer was colorectal in 54.8% of patients. Among the extracolonic index cancers endometrial/uterine was the most common (29.6%) followed by skin (24.1%, of which 11.1% were confirmed cases of MuirTorre). Other index cancers were renal/ureter/bladder (10.2%), upper GI/small intestine (6.5%), ovary (5.6%) and hepatobiliary/pancreas (3.7%). It was interesting to note that the index tumor was breast cancer in 5 patients (4.6%) although breast cancer is not considered part of Lynch syndrome [1-3]. Other non-Lynch syndrome index cancers recorded were prostate (n=3, 2.8%), thyroid (n=2, 1.85%), cervix/vagina (n=2, 1.85%) and 1 case each of thymoma, leukemia, lymphoma soft palate, adenocarcinoma of the lung and fibroxanthoma peritoneum. In addition, there was 1 index brain tumor and 4 patients presented with metastatic disease (lung, liver, unknown primary).