CHST7 Gene Methylation and Sex-Specific Effects on Colorectal Cancer Risk

BackgroundX chromosome aberrations are involved in carcinogenesis and are associated with gender differences in cancer development. Abnormal DNA methylation also contributes to cancer. Carbohydrate Sulfotransferase 7 (CHST7), encoded by the X chromosome, is abnormally expressed during tumor development. However, its impact on colorectal cancer (CRC) and the effect of CHST7 methylation on sex-specific CRC risk remain unclear.AimsTo investigate the effect of CHST7 methylation in white blood cells on CRC risk and to evaluate its impact on gender-specific differences.MethodsCHST7 methylation in white blood cells was determined using methylation-sensitive high-resolution melting. A propensity score analysis was performed to control potential confounders. Furthermore, extensive sensitivity analyses were applied to assess the robustness of our findings. In addition, we validated the initial findings with a GEO dataset (GSE51032).ResultsCHST7 hypermethylation in white blood cells was associated with an increased CRC risk [odds ratio (OR)(adj)=4.447, 95% confidence interval (CI) 2.662-7.430; p<0.001]. The association was validated with the GEO dataset (ORadj=2.802, 95% CI 1.235-6.360; p=0.014). In particular, CHST7 hypermethylation significantly increased the CRC risk in females (ORadj=7.704, 95% CI 4.222-14.058; p<0.001) and younger patients (<= 60years) (ORadj=5.755, 95% CI 2.540-13.038; p<0.001). Subgroup analyses by tumor location and Duke's stage also observed these associations.ConclusionCHST7 methylation in white blood cells is positively associated with CRC risk, especially in females, and may potentially serve as a blood-based predictive biomarker for CRC risk.