{"doi":"10.1093/jncics/pkaa027","title":"Penetrance of Colorectal Cancer Among Mismatch Repair Gene Mutation Carriers: A Meta-Analysis","abstract":"Abstract 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 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 years, for male and female carriers, respectively, risks for MLH1 were 43.9% (95% confidence interval [CI] = 39.6% to 46.6%) and 37.3% (95% CI = 32.2% to 40.2%), for MSH2 were 53.9% (95% CI = 49.0% to 56.3%) and 38.6% (95% CI = 34.1% to 42.0%), and for MSH6 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.","journal":"JNCI Cancer Spectrum","year":2020,"id":94726,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9477,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":471585,"name":"Yan Wang","orcid":"0000-0003-1084-1957","position":1,"is_corresponding":false},{"id":284715,"name":"Kevin S. Hughes","orcid":"0000-0003-4084-6484","position":2,"is_corresponding":false},{"id":2251,"name":"Giovanni Parmigiani","orcid":"0000-0002-8783-5961","position":3,"is_corresponding":false},{"id":106070,"name":"Danielle Braun","orcid":"0000-0002-5177-8598","position":4,"is_corresponding":false},{"id":472431,"name":"Cathy Wang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T22:33:00.770265Z","pmid":"32923933","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}