Lynch syndrome (LS) is an inherited syndrome of predisposition to cancer with an increased risk for colorectal cancer ranging from 30% to 80%. Prostate cancer has been described as a component tumor of LS, but the lifetime risk of prostate cancer in patients with LS has not been quantified because of inherent difficulties. In a new analysis, researchers have used genetic data to define the risk of prostate cancer in men with LS (Raymond VM, et al. J Clin Oncol. 2013;31:1713-1718).
Mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 are the leading causes of LS. The investigators identified 198 families with pathogenic mutations in the MMR genes MLH1, MSH2, MSH6, and PMS2 who have registered with 2 cancer genetics clinics. Each family was comprised of all first-degree through fourth-degree relatives of the first person in the family to undergo MMR-related gene testing. Mutation status was known for 597 men; of these patients, 412 had at least 1 of the MMR-based mutations, and 185 men had no mutations.
Medical records were used to analyze prostate cancer data. Of the 4127 men included in the prostate cancer analysis, 97 (2.4%) had a personal history of prostate cancer; the median age at prostate cancer diagnosis was 65 years. The cumulative lifetime risk (to age 80) for prostate cancer was 30% in patients with 1 of the MMR-based mutations compared with 17.84% for the general population (P = .07).
The US Preventive Services Task Force recently recommended against prostate-specific antigen (PSA) screening in asymptomatic men aged <75 years. However, based on the findings in this study, early screening for prostate cancer, including PSA testing, may be of benefit in men who are at an increased risk for prostate cancer, including men with a family history of prostate cancer or a genetic predisposition to prostate cancer, such as LS.
