PURPOSE: Prostate cancer has been described as a component tumor of Lynch syndrome (LS), with tumors obtained from mutation carriers demonstrating the DNA mismatch repair deficiency phenotype.
Previous studies quantifying prostate cancer risk in LS have provided conflicting results.
METHODS: We examined cancer histories of probands and their first- through fourth-degree relatives for 198 independent mutation-positive LS families enrolled in two US familial cancer registries. Modified segregation analysis was used to calculate age-specific cumulative risk or penetrance estimates, with accompanying Wald-type CIs. Cumulative lifetime risks and hazard ratio (HR) estimates for prostate cancer were calculated and compared with those of the general population.
RESULTS: Ninety-seven cases of prostate cancer were observed in 4,127 men. Median age at prostate cancer diagnosis was 65 years (range, 38 to 89 years), with 11.53% of affected individuals diagnosed before age 50 years. The cumulative risk of prostate cancer at ages 60 and 80 years was 6.30% (95% CI, 2.47 to 9.96) and 30.0% (95% CI, 16.54 to 41.30), as compared with the population risk of 2.59% and 17.84%, respectively. The overall prostate cancer HR among carriers was 1.99 (95% CI, 1.31 to 3.03).
CONCLUSION: The cumulative lifetime risk of prostate cancer in individuals with LS is two-fold higher than in the general population and is slightly higher in carriers diagnosed before age 60 years (HR, 2.48; 95% CI, 1.34 to 4.59). These estimates are clinically valuable to quantify risk for both patients and providers.
Written by:
Raymond VM, Mukherjee B, Wang F, Huang SC, Stoffel EM, Kastrinos F, Syngal S, Cooney KA, Gruber SB. Are you the author?
University of Michigan; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; Columbia University Medical Center, Herbert Irving Comprehensive Cancer Center, New York, NY; University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA.
Reference: J Clin Oncol. 2013 Mar 25. Epub ahead of print.
doi: 10.1200/JCO.2012.44.1238
PubMed Abstract
PMID: 23530095
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