دورية أكاديمية
Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer.
| العنوان: | Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer. |
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| المؤلفون: | Win, Aung Ko, Jenkins, Mark A, Dowty, James G, Antoniou, Antonis C, Lee, Andrew, Giles, Graham G, Buchanan, Daniel D, Clendenning, Mark, Rosty, Christophe, Ahnen, Dennis J, Thibodeau, Stephen N, Casey, Graham, Gallinger, Steven, Le Marchand, Loïc, Haile, Robert W, Potter, John D, Zheng, Yingye, Lindor, Noralane M, Newcomb, Polly A, Hopper, John L, MacInnis, Robert J |
| بيانات النشر: | American Association for Cancer Research (AACR) //dx.doi.org/10.1158/1055-9965.epi-16-0693 Cancer Epidemiol Biomarkers Prev |
| سنة النشر: | 2017 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Adult, Aged, Colorectal Neoplasms, DNA Glycosylases, DNA Mismatch Repair, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Multifactorial Inheritance, MutL Protein Homolog 1, Mutation, Penetrance, Population Surveillance, Prevalence, Risk Factors |
| الوصف: | 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. ; This work was supported by grant UM1 CA167551 from the National Cancer Institute, National Institutes of Health (NIH) and through cooperative agreements with the following Colon Cancer Family Registry (CCFR) centers: Australasian Colorectal Cancer Family Registry (U01/U24 CA097735), Mayo Clinic Cooperative Family Registry for Colon Cancer ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print-Electronic; application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/262022Test |
| DOI: | 10.17863/CAM.7260 |
| الإتاحة: | https://doi.org/10.17863/CAM.7260Test https://www.repository.cam.ac.uk/handle/1810/262022Test |
| رقم الانضمام: | edsbas.E9145449 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.7260 |
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