@entity5 requires accumulation of several mutations (mutation threshold). We hypothesize that @entity28 raises the risk of microsatellite stable (MSS) @entity694 ( @entity694 ) at least in part by decreasing the mutation threshold. Thus, we posit that @entity28 @entity1 require fewer mutations, particularly driver mutations, compared to their normal BMI counterparts. Further, we suggest that the reduced number of required mutations in @entity28 @entity1 could be due to several factors, including the high levels of cytokines that accompany @entity28 . Cytokine-activated @entity3963 , AKT, and JAK/STAT signaling could synergize with @entity694 -initiating mutations to promote intestinal neoplastic development. Therefore, driver mutations that induce these specific pathways may not be "required" for neoplastic development in @entity28 ; alteration in cell signaling consequent to @entity28 can substitute for some driver mutations in neoplastic progression. This hypothesis is supported by preliminary analyses of data from The @entity5 (TCGA). Thus, we observed that, compared to normal weight @entity1 , @entity5 genomes of @entity694 @entity1 exhibit fewer somatic mutations, and correspondingly lower numbers of mutations in driver genes (P = 0.026).The most striking observation was the lower number of @entity984 mutations detected in @entity1 with high body-mass index (BMI). These intriguing observations require further validation with increased number of @entity1 , taking into account all possible confounding factors. If the hypothesis is confirmed, future studies should also address several possible explanations for the observed lower mutation threshold in @entity694 @entity1 .

Hypothesis: Obesity Is Associated with a Lower Mutation Threshold in XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity28 :: ('MESH:D009765', 'Disease') :: ['obese', 'obesity'] @entity5 :: ('MESH:D009369', 'Disease') :: ['Cancer Genome Atlas', 'cancer', 'Neoplastic progression'] @entity984 :: ('3845', 'Gene') :: ['KRAS'] @entity3963 :: ('5594', 'Gene') :: ['ERK'] @entity694 :: ('MESH:D003110', 'Disease') :: ['colon cancer', 'CC', 'obese MSS CC']
@entity694 :: (MESH:D003110,Disease) :: ['Colon Cancer']
