Penetrance of Colorectal Cancer Among Mismatch Repair Gene Mutation Carriers: A Meta-Analysis
A partir d'une revue systématique de la littérature publiée jusqu'en mars 2019 (10 études), cette méta-analyse évalue le risque de cancer colorectal chez les personnes porteuses d'une mutation d'un gène de réparation des mésappariements de l'ADN ou syndrome de Lynch, en fonction du gène considéré, du sexe et de l'âge
Lynch syndrome, the most common colorectal cancer (CRC) syndrome, is caused by germline mutations in 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.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.Our comprehensive search identified 10 studies (8 on MLH1, 9 on MSH2, and 3 on MSH6). We estimated the cumulative risk of CRC by age and sex in heterozygous mutation carriers. At age 70, for males and females respectively, risks for MLH1 are 43.9% (95% CI: 39.6, 46.6) and 37.3%(95% CI: 32.2, 40.2); for MSH2 53.9% (95% CI: 49.0, 56.3) and 38.6% (95% CI: 34.1, 42.0); and for MSH6 12.0% (95% CI: 2.4, 24.6) and 12.3% (95% CI: 3.5, 23.2).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.
JNCI Cancer Spectrum , article en libre accès, 2019