AI Article Synopsis

  • Different inbred strains of mice respond variably to colitis-associated colorectal cancer (CA-CRC), with the FVB/NJ strain showing the highest susceptibility and tumor burden compared to other strains like A/J and B6.
  • A significant increase in tumor development in FVB/NJ mice was observed as early as 8 weeks post-treatment with azoxymethane/dextran sulfate sodium, with findings indicating a 5.5-fold increase in tumors compared to other strains.
  • Genetic analysis revealed a new susceptibility locus, Ccs6, on chromosome 6, associated with increased tumor multiplicity; further studies are exploring its potential role in cancer development and inflammatory responses.

Article 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).

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http://dx.doi.org/10.1007/s00335-016-9625-zDOI Listing

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