Haoran Bi1, Yupeng Liu1, Rui Pu1, Tingting Xia1, Hongru Sun1, Hao Huang1, Lei Zhang1, Yuanyuan Zhang1, Ying Liu1, Jing Xu1, Jiesheng Rong2, Yashuang Zhao3. 1. Department of Epidemiology, Public Health College, Harbin Medical University, 157 Baojian Street, Nangang District, Harbin, 150081, Heilongjiang Province, People's Republic of China. 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. 3. Department of Epidemiology, Public Health College, Harbin Medical University, 157 Baojian Street, Nangang District, Harbin, 150081, Heilongjiang Province, People's Republic of China. zhao_yashuang@263.net.
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.
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.
Entities:
Keywords:
CHST7; Colorectal cancer; DNA methylation; Propensity score; Sex difference; White blood cell
Authors: Rhiannon J Walters; Elizabeth J Williamson; Dallas R English; Joanne P Young; Christophe Rosty; Mark Clendenning; Michael D Walsh; Susan Parry; Dennis J Ahnen; John A Baron; Aung Ko Win; Graham G Giles; John L Hopper; Mark A Jenkins; Daniel D Buchanan Journal: Epigenetics Date: 2013-06-17 Impact factor: 4.528
Authors: Andrew E Teschendorff; Usha Menon; Aleksandra Gentry-Maharaj; Susan J Ramus; Simon A Gayther; Sophia Apostolidou; Allison Jones; Matthias Lechner; Stephan Beck; Ian J Jacobs; Martin Widschwendter Journal: PLoS One Date: 2009-12-18 Impact factor: 3.240