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

Abstract

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)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 (≤ 60 years) (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.

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.

• Authors: Haoran Bi, Yupeng Liu, Rui Pu, Tingting Xia, Hongru Sun, Hao Huang, Lei Zhang, Yuanyuan Zhang, Ying Liu, Jing Xu, Jiesheng Rong, Yashuang Zhao
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 64 Issue 8 Pg. 2158-2166 (08 2019) ISSN: 1573-2568 [Electronic] United States
• PMID: 30815821 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Sulfotransferases
• carbohydrate sulfotransferases

Topics

• Biomarkers, Tumor (genetics)
• Case-Control Studies
• Colorectal Neoplasms (genetics, pathology)
• DNA Methylation
• Female
• Humans
• Male
• Middle Aged
• Propensity Score
• Risk
• Sex Factors
• Sulfotransferases (genetics)