Analysis in the Prospective Lynch Syndrome Database identifies sarcoma as part of the Lynch syndrome tumor spectrum

摘要

Dear editor, Lynch syndrome (LS) is the most common hereditary cancer syndrome. It results from heterozygous pathogenic germline variants in the mismatch repair (MMR) genes that are carried by over 1 in 200 individuals. Pathogenic variants in each of the MMR genes, path_MLH1, path_MSH2, path_MSH6 and path_PMS2, result in different risks for cancers in organs including the colorectum, endometrium, ovaries, stomach, small bowel, bile duct, pancreas and upper urinary tract. These cancers, but not sarcomas, are commonly cited as LS spectrum cancers. Sarcomas include osteosarcomas (OS) that have a worldwide incidence of 4.3 per million in males and 3.4 per million females per year, and soft tissue sarcomas (STS) that are a heterogeneous group of cancers of mesenchymal origin with a population incidence of 3.5 per 100 000 people per year in the US. In the most recent study from the Prospective Lynch Syndrome Database (PLSD) we reported 14 cases of sarcoma among 1808 prospectively observed tumors in 6350 carriers of path_MMR variants with 51 646 follow-up years (FUY).