Elevated Risk of Prostate Cancer Among Men With Lynch Syndrome

Introduction

Lynch syndrome (LS) is an inherited cancer predisposition
syndrome with elevated lifetime risk of colorectal cancer (CRC) ranging from 35% to 80%.1-4 Germline mutations in the mismatch repair
(MMR) genes MLH1, MSH2, MSH6, and PMS2 are the leading cause of LS. In addition to CRC, other cancers are known to be associated with LS. For women, the risk of endometrial cancer (EC) is high, ranging from 34% to 71%.1-4 Other cancers, including gastric, ovarian, urinary tract, pancreatic, brain, and sebaceous tumors, are also associated with LS,
and there is an elevated risk in mutation carriers.5-8 Prostate cancer is the most common cancer in men, with a Surveillance, Epidemiology, and End Results (SEER)9 estimated lifetime risk of 17.84% and median age at diagnosis of 67 years. Prostate cancer has been described as a component tumor of LS10,11; however, the lifetime risk of prostate cancer in men with LS has been difficult to quantify. Prostate cancer has a high background population risk, which makes it difficult to identify significant modifications to the lifetime risk estimate. Most studies
that have aimed to estimate prostate cancer risk in LS have been performed in families identified through high-risk cancer genetics clinics, with strong personal and/or family histories of cancer,
subjecting them to ascertainment bias and leading to an overestimation of cancer risk........