Insulin-like growth factor 2 hypermethylation in peripheral blood leukocytes and colorectal cancer risk and prognosis: a propensity score analysis

To comprehensively assess and validate the associations between insulin-like growth factor 2 ( ) gene methylation in peripheral blood leukocytes (PBLs) and colorectal cancer (CRC) risk and prognosis. The association between methylation in PBLs and CRC risk was initially evaluated in a case-control study and then validated in a nested case-control study and a twins' case-control study, respectively. Meanwhile, an initial CRC patient cohort was used to assess the effect of methylation on CRC prognosis and then the finding was validated in the EPIC-Italy CRC cohort and TCGA datasets. A propensity score (PS) analysis was performed to control for confounders, and extensive sensitivity analyses were performed to assess the robustness of our findings. PBL hypermethylation was associated with an increased risk of CRC in the initial study (OR , 2.57, 95% CI: 1.65 to 4.03,