title: Mapping hyper-susceptibility to colitis-associated colorectal cancer in FVB/NJ mice.
abstract: Inbred strains of mice differ in susceptibility to colitis-associated colorectal cancer (CA-CRC). We tested 10 inbred strains of mice for their response to azoxymethane/dextran sulfate sodium-induced CA-CRC and identified a bimodal inter-strain distribution pattern when tumor multiplicity was used as a phenotypic marker of susceptibility. The FVB/NJ strain was particularly susceptible showing a higher tumor burden than any other susceptible strains (12.5-week post-treatment initiation). FVB/NJ hyper-susceptibility was detected as early as 8-week post-treatment initiation with FVB/NJ mice developing 5.5-fold more tumors than susceptible A/J or resistant B6 control mice. Linkage analysis by whole genome scan in informative (FVB/NJ×C3H/HeJ)F2 mice identified a novel susceptibility locus designated as C olon c ancer s usceptibility 6 (Ccs6) on proximal mouse chromosome 6. When gender was used as a covariate, a LOD score of 5.4 was computed with the peak marker being positioned at rs13478727, 43.8 Mbp. Mice homozygous for FVB/NJ alleles at this locus had increased tumor multiplicity compared to homozygous C3H/HeJ mice. Positional candidates in this region of chromosome 6 were analyzed with respect to a possible role in carcinogenesis and a role in inflammatory response using a new epigenetic gene scoring tool (Myeloid Inflammation Score).
authors.affiliation: Department of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.|Goodman Cancer Research Centre, McGill University, Montreal, QC, H3A 1A3, Canada.
authors.forename: Lauren
authors.initials: L
authors.lastname: Van Der Kraak
authors.affiliation: Department of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.|Goodman Cancer Research Centre, McGill University, Montreal, QC, H3A 1A3, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Langlais
authors.affiliation: Department of Laboratory Medicine and Pathology, St. Michael's Hospital and University of Toronto, Toronto, ON, M5B 1W8, Canada.
authors.forename: Serge
authors.initials: S
authors.lastname: Jothy
authors.affiliation: Department of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.|Goodman Cancer Research Centre, McGill University, Montreal, QC, H3A 1A3, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Beauchemin
authors.affiliation: Department of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada. philippe.gros@mcgill.ca.|Goodman Cancer Research Centre, McGill University, Montreal, QC, H3A 1A3, Canada. philippe.gros@mcgill.ca.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gros
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics; D003092:Colitis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D051379:Mice; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics*