Penetrance of Colorectal Cancer Among Mismatch Repair Gene Mutation Carriers: A Meta-Analysis.

BACKGROUND

Lynch syndrome, the most common colorectal cancer (CRC) syndrome, is caused by germline mismatch repair (MMR) genes. Precise estimates of age-specific risks are crucial for sound counseling of individuals managing a genetic predisposition to cancer, but published risk estimates vary. The objective of this work is to provide gene-, sex-, and age-specific risk estimates of CRC for MMR mutation carriers that comprehensively reflect the best available data.

METHODS

We conducted a meta-analysis to combine risk information from multiple studies on Lynch syndrome-associated CRC. We used a likelihood-based approach to integrate reported measures of CRC risk and deconvolved aggregated information to estimate gene- and sex-specific risk.

RESULTS

Our comprehensive search identified 10 studies (8 on , 9 on , and 3 on ). We estimated the cumulative risk of CRC by age and sex in heterozygous mutation carriers. At age 70 years, for male and female carriers, respectively, risks for were 43.9% (95% confidence interval [CI] = 39.6% to 46.6%) and 37.3% (95% CI = 32.2% to 40.2%), for were 53.9% (95% CI = 49.0% to 56.3%) and 38.6% (95% CI = 34.1% to 42.0%), and for were 12.0% (95% CI = 2.4% to 24.6%) and 12.3% (95% CI = 3.5% to 23.2%).

CONCLUSIONS

Our results provide up-to-date and comprehensive age-specific CRC risk estimates for counseling and risk prediction tools. These will have a direct clinical impact by improving prevention and management strategies for both individuals who are MMR mutation carriers and those considering testing.