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

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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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Acknowledgments

This work was supported by the National Natural Science Foundation of China grants, Grant numbers 81473055 and 30972539.

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Authors and Affiliations

  1. Department of Epidemiology, Public Health College, Harbin Medical University, 157 Baojian Street, Nangang District, Harbin, 150081, Heilongjiang Province, People’s Republic of China

    Haoran Bi, Yupeng Liu, Rui Pu, Tingting **a, Hongru Sun, Hao Huang, Lei Zhang, Yuanyuan Zhang, Ying Liu, **g Xu & Yashuang Zhao

  2. Department of Orthopedics Surgery, The Second Affiliated Hospital of Harbin Medical University, 246, Xuefu Street, Harbin, 150081, Heilongjiang Province, People’s Republic of China

    Jiesheng Rong

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  1. Haoran Bi
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Correspondence to Yashuang Zhao.

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Bi, H., Liu, Y., Pu, R. et al. CHST7 Gene Methylation and Sex-Specific Effects on Colorectal Cancer Risk. Dig Dis Sci 64, 2158–2166 (2019). https://doi.org/10.1007/s10620-019-05530-9

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