{"entity":{"id":"paper-win-cancer-epidemiol-biomarkers-prev","kind":"paper","name":"Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 27799157 and published in Cancer Epidemiology, Biomarkers & Prevention; the citing page links this DOI, which is how the record was matched.","summary":"Background: Although high-risk mutations in identified major susceptibility genes (DNA mismatch repair genes and MUTYH) account for some familial aggregation of colorectal cancer, their population prevalence and the causes of the remaining familial aggregation are not known. Methods: We studied the families of 5,744 colorectal cancer cases (probands) recruited from population cancer registries in the United States, Canada, and Australia and screened probands for mutations in mismatch repair genes and MUTYH We conducted modified segregation analyses using the cancer history of first-degree relatives, conditional on the proband's age at diagnosis. We estimated the prevalence of mutations in the identified genes, the prevalence of HR for unidentified major gene mutations, and the variance of the residual polygenic component. Results: We estimated that 1 in 279 of the population carry mutations in mismatch repair genes ( MLH1 = 1 in 1,946, MSH2 = 1 in 2,841, MSH6 = 1 in 758, PMS2 = 1 in 714), 1 in 45 carry mutations in MUTYH, and 1 in 504 carry mutations associated with an average 31-fold increased risk of colorectal cancer in unidentified major genes. The estimated polygenic variance was reduced by 30% to 50% after allowing for unidentified major genes and decreased from 3.3 for age <40 years to 0.5 for age ≥70 years (equivalent to sibling relative risks of 5.1 to 1.3, respectively). Conclusions: Unidentified major genes might explain one third to one half of the missing heritability of colorectal cancer. Impact: Our findings could aid gene discovery and development of better colorectal cancer risk prediction models. Cancer Epidemiol Biomarkers Prev; 26(3); 404-12. ©2016 AACR.\n\nIndexed on Europe PMC as PubMed record 27799157 (DOI 10.1158/1055-9965.epi-16-0693). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Epidemiol Biomarkers Prev 2017","url":"https://doi.org/10.1158/1055-9965.epi-16-0693"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27799157/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27799157"}],"tags":["europepmc-ingest"],"related":["b-hereditary-risk"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-epidemiology-biomarkers-prevention"],"dependsOn":[],"notes":[],"journal":"Cancer Epidemiology, Biomarkers & Prevention","year":2017,"doi":"10.1158/1055-9965.epi-16-0693","pmid":"27799157","authors":"Win AK, Jenkins MA, Dowty JG, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-win-cancer-epidemiol-biomarkers-prev/","neighbours":{"bottleneck":[{"id":"b-hereditary-risk","kind":"bottleneck","name":"Inherited risk is mostly unidentified","route":"/bottlenecks/b-hereditary-risk/"}],"journal":[{"id":"cancer-epidemiology-biomarkers-prevention","kind":"journal","name":"Cancer Epidemiology, Biomarkers & Prevention","route":"/journals/cancer-epidemiology-biomarkers-prevention/"}]}}