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28.02.2019 | Original Article | Ausgabe 8/2019

Digestive Diseases and Sciences 8/2019

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

Zeitschrift:
Digestive Diseases and Sciences > Ausgabe 8/2019
Autoren:
Haoran Bi, Yupeng Liu, Rui Pu, Tingting Xia, Hongru Sun, Hao Huang, Lei Zhang, Yuanyuan Zhang, Ying Liu, Jing Xu, Jiesheng Rong, Yashuang Zhao
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s10620-019-05530-9) contains supplementary material, which is available to authorized users.

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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.

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