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

Background: X 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.

Aims: To investigate the effect of CHST7 methylation in white blood cells on CRC risk and to evaluate its impact on gender-specific differences.

Methods: CHST7 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).

Results: CHST7 hypermethylation in white blood cells was associated with an increased CRC risk [odds ratio (OR) = 4.447, 95% confidence interval (CI) 2.662-7.430; p < 0.001]. The association was validated with the GEO dataset (OR = 2.802, 95% CI 1.235-6.360; p = 0.014). In particular, CHST7 hypermethylation significantly increased the CRC risk in females (OR = 7.704, 95% CI 4.222-14.058; p < 0.001) and younger patients (≤ 60 years) (OR = 5.755, 95% CI 2.540-13.038; p < 0.001). Subgroup analyses by tumor location and Duke's stage also observed these associations.

Conclusion: CHST7 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.