title: A two-locus system controls susceptibility to colitis-associated colon cancer in mice.
abstract: We have previously shown that the differential susceptibility of A/J (susceptible) and C57BL/6J (B6, resistant) mouse strains to azoxymethane (AOM)-induced colorectal cancer (CRC) is controlled by the chromosome 3 locus, Ccs3. We report that A/J and B6 mice also show differential susceptibility to colitis-associated colorectal cancer (CA-CRC) induced by combined administration of AOM and dextran sulfate. This differential susceptibility is not controlled by Ccs3, but is under distinct genetic control. Linkage analyses in (A/J x B6)F2 mice detected a major CA-CRC susceptibility locus on chromosome 9 (Ccs4) which controls tumor multiplicity and tumor surface area. Susceptibility alleles at Ccs4 are inherited in a recessive fashion, with A/J alleles being associated with susceptibility. We also detected a second locus on chromosome 14 that acts in an additive fashion with Ccs4. Strikingly, F2 mice homozygous for A/J alleles at both loci (Ccs4 and chromosome 14) are as susceptible to CA-CRC as the A/J controls while mice homozygous for B6 alleles are as resistant as the B6 controls, thus supporting the role of two interacting loci in this CA-CRC model. This indicates that susceptibility to chemically-induced CRC and susceptibility to CA-CRC are under distinct genetic control in mice, and probably involve distinct cellular pathways.
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Quebec, Canada.|Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Lauren
authors.initials: L
authors.lastname: Van Der Kraak
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Quebec, Canada.|Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Meunier
authors.affiliation: Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Claire
authors.initials: C
authors.lastname: Turbide
authors.affiliation: Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Serge
authors.initials: S
authors.lastname: Jothy
authors.affiliation: Institut de Recherche en Immunologie et en Cancérologie, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Louis
authors.initials: L
authors.lastname: Gaboury
authors.affiliation: Department of Pathology, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Victoria
authors.initials: V
authors.lastname: Marcus
authors.affiliation: Department of Pathology, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Sing Yun
authors.initials: SY
authors.lastname: Chang
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Quebec, Canada.|Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.|Departments of Medicine and Oncology, McGill University, Montreal, Quebec, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Beauchemin
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Quebec, Canada.|Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gros
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D003092:Colitis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D008040:Genetic Linkage; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D040641:Quantitative Trait Loci / Q000235:genetics*
chemical_list: D002273:Carcinogens; D001397:Azoxymethane