de Kort S, et al. - Among participants from the Netherlands Cohort Study (n=120,852), researchers examined the combined impacts on colorectal cancer (CRC) risk of type 2 diabetes mellitus (T2DM) and genetic variation in the insulin-like growth factor (IGF) pathway. In 1986, when these subjects were 55-69 years old, they completed a baseline questionnaire (case-cohort, n subcohort=5,000, n cases = 3,441 after 16.3 years follow-up). In subcohort members and in CRC cases, the respective baseline T2DM prevalence was 3.1% and 3.8%. When they compared combined categories to non-T2DM subjects in the lowest genetic risk score (GRS) tertile as a reference, they found significantly increased CRC risks in those in the highest GRS tertiles with and without T2DM; this was especially seen in those with T2DM. A significantly reduced CRC risk was observed in those without T2DM in relation to carrying two IGF1 19-CA variant repeat alleles vs IGF1 19-CA wild type carriers without T2DM. They noted the absence of this link in the presence of T2DM. Overall, the risk of CRC related to T2DM may be further enhanced by the presence of unfavorable alleles in the IGF pathway.