A New Polygenic Model for Nonfamilial Colorectal Cancer Inheritance Based on the Genetic Architecture of the Azoxymethane-Induced Mouse Model
- 주제(키워드) cancer susceptibility , mouse models , heterogeneity , genetic architecture
- 주제(기타) Genetics & Heredity
- 설명문(일반) [Bissahoyo, Anika C.; Xie, Yuying; Pearsall, R. Scott; Pardo-Manuel de Villena, Fernando] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA; [Yang, Lynda; McMillan, Leonard] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27599 USA; [Lee, Daekee] Ewha Womans Univ, Div Life & Pharmaceut Sci, Seoul 03760, South Korea; [Elliott, Rosemary W.; Demant, Peter] Roswell Park Canc Inst, Dept Mol & Cellular Biol, Buffalo, NY 14263 USA; [Angel, Joe M.; Threadgill, David W.] Texas A&M Univ, Dept Mol & Cellular Med, Reynolds 440, College Stn, TX 77843 USA; [Threadgill, David W.] Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA
- 등재 SCIE, SCOPUS
- OA유형 Green Published, Bronze
- 발행기관 GENETICS SOCIETY AMERICA
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000168768
- 본문언어 영어
- Published As https://dx.doi.org/10.1534/genetics.119.302833
초록/요약
The azoxymethane model of colorectal cancer (CRC) was used to gain insights into the genetic heterogeneity of nonfamilial CRC. We observed significant differences in susceptibility parameters across 40 mouse inbred strains, with 6 new and 18 of 24 previously identified mouse CRC modifier alleles detected using genome-wide association analysis. Tumor incidence varied in F1 as well as intercrosses and backcrosses between resistant and susceptible strains. Analysis of inheritance patterns indicates that resistance to CRC development is inherited as a dominant characteristic genome-wide, and that susceptibility appears to occur in individuals lacking a large-effect, or sufficient numbers of small-effect, polygenic resistance alleles. Our results suggest a new polygenic model for inheritance of nonfamilial CRC, and that genetic studies in humans aimed at identifying individuals with elevated susceptibility should be pursued through the lens of absence of dominant resistance alleles rather than for the presence of susceptibility alleles. The azoxymethane carcinogen model of non-familial colorectal cancer has been used in mice to identify six new susceptibility loci and confirm 18 of 24 previous detected susceptibility loci. Using a population-based approach, the genetic architecture of colon cancer...
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