Professor Lazarova from the US Federal Medical School has published a study in J Cancer on the effects of obesity on colon cancer, hypothesizing that obesity lowers the mutational threshold required to develop colon cancer. Obesity has become a worldwide problem, with 11% of colon cancer patients being obese, and there is evidence that obesity increases the risk of developing colon cancer. Professor Lazarova’s hypothesis that colon cancer patients with normal BMI are more likely to develop driver mutations than those with BMI ≥ 25 was confirmed in a Drosophila model: the JNK signaling pathway induces the production of cytokines that stimulate Ras mutated cells to develop into cancer cells. This cytokine is secreted by adipocytes and macrophages in obese patients. Do such obesity-associated cytokines induce mutations in pathways associated with colon cancer that together promote tumor development? To this end, Professor Lazarova used exon sequencing and clinical data from The Cancer Genome Atlas (TCGA) to analyze clinical and sequencing information from 175 patients with colon adenocarcinoma, more than half of whom had missing weight and height information. The median number of somatic mutations was 176.0, 123.0 and 129.5 in the normal, overweight and obese BMI groups, respectively, with the most somatic mutations occurring in the normal BMI group. Because the pathogenesis of microsatellite instability (MSI) colon cancer and microsatellite stability (MSS) colon cancer were different and the number of mutated genes was very different, the investigators analyzed the two groups separately. A total of 39 cases with somatic mutations ≥ 500 were MSI and 136 cases with somatic mutations < 500 were MSS. It was found that the number of mutations in MSS colon cancer patients tended to decrease with increasing BMI, with 5.3%, 4.6%, and 4.1% of driver mutations in the normal, overweight, and obese BMI groups, respectively, while MSI patients did not show this trend. Although the results suggest that obese individuals have fewer driver mutations in MSS colon cancer, the reasons for this are unknown, Professor Lazarova analyzed several possibilities: 1. The epigenetic alterations in obese individuals compensate for the reduced gap in driver gene mutations. If this assertion is confirmed, there is a need to incorporate weight management into the colon cancer prevention system, and there is reason to believe that patients with fewer mutations are more sensitive to molecularly targeted therapies, and that obesity-related signals may also lead to treatment tolerance, thus providing a basis for MSS colon cancer prevention and treatment of obese patients. This could provide a basis for the prevention of MSS colon cancer and the treatment of obese patients.