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

Overview

Journal Dig Dis Sci

Specialty Gastroenterology

Date 2019 Mar 1

PMID 30815821

Citations 7

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

Affiliations

Soon will be listed here.

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) = 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.

Citing Articles

Studies in Cancer Epigenetics through a Sex and Gendered Lens: A Comprehensive Scoping Review.

Huerne K, Jackson S, Lall R, Palmour N, Berner A, Dupras C Cancers (Basel). 2023; 15(17).

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Carbohydrate sulfotransferases: a review of emerging diagnostic and prognostic applications.

Begolli G, Markovic I, Knezevic J, Debeljak Z Biochem Med (Zagreb). 2023; 33(3):030503.

PMID: 37545696 PMC: 10373059. DOI: 10.11613/BM.2023.030503.

Molecular basis of sex differences in cancer: Perspective from Asia.

Ornos E, Cando L, Catral C, Quebral E, Tantengco O, Arevalo M iScience. 2023; 26(7):107101.

PMID: 37404373 PMC: 10316661. DOI: 10.1016/j.isci.2023.107101.

Long non-coding RNA ZNF674-AS1 antagonizes oxaliplatin resistance of gastric cancer via regulating EZH2-mediated methylation of CHST7.

Ye K, Wang Y Aging (Albany NY). 2022; 14(13):5523-5536.

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A methylation-based prognostic model predicts survival in patients with colorectal cancer.

Tan S, Gui W, Wang S, Sun C, Xu X, Liu L J Gastrointest Oncol. 2021; 12(4):1590-1600.

PMID: 34532113 PMC: 8421910. DOI: 10.21037/jgo-21-376.

References

Debeljak Z, Dundovic S, Badovinac S, Mandic S, Samarzija M, Dmitrovic B . Serum carbohydrate sulfotransferase 7 in lung cancer and non-malignant pulmonary inflammations. Clin Chem Lab Med. 2018; 56(8):1328-1335. DOI: 10.1515/cclm-2017-1157. View

Robertson K . DNA methylation and human disease. Nat Rev Genet. 2005; 6(8):597-610. DOI: 10.1038/nrg1655. View

Ally M, Al-Ghnaniem R, Pufulete M . The relationship between gene-specific DNA methylation in leukocytes and normal colorectal mucosa in subjects with and without colorectal tumors. Cancer Epidemiol Biomarkers Prev. 2009; 18(3):922-8. DOI: 10.1158/1055-9965.EPI-08-0703. View

Zheng Z, Zheng R, Zhang S, Chen W . Colorectal cancer incidence and mortality in China, 2010. Asian Pac J Cancer Prev. 2014; 15(19):8455-60. DOI: 10.7314/apjcp.2014.15.19.8455. View

De Angelis P, Clausen O, Schjolberg A, Stokke T . Chromosomal gains and losses in primary colorectal carcinomas detected by CGH and their associations with tumour DNA ploidy, genotypes and phenotypes. Br J Cancer. 1999; 80(3-4):526-35. PMC: 2362312. DOI: 10.1038/sj.bjc.6690388. View

Teschendorff A, Menon U, Gentry-Maharaj A, Ramus S, Gayther S, Apostolidou S . An epigenetic signature in peripheral blood predicts active ovarian cancer. PLoS One. 2009; 4(12):e8274. PMC: 2793425. DOI: 10.1371/journal.pone.0008274. View

Lyon M . Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature. 1961; 190:372-3. DOI: 10.1038/190372a0. View

Bardhan K, Liu K . Epigenetics and colorectal cancer pathogenesis. Cancers (Basel). 2013; 5(2):676-713. PMC: 3730326. DOI: 10.3390/cancers5020676. View

Shivapurkar N, Gazdar A . DNA methylation based biomarkers in non-invasive cancer screening. Curr Mol Med. 2010; 10(2):123-32. PMC: 3397200. DOI: 10.2174/156652410790963303. View

10.

Walters R, Williamson E, English D, Young J, Rosty C, Clendenning M . Association between hypermethylation of DNA repetitive elements in white blood cell DNA and early-onset colorectal cancer. Epigenetics. 2013; 8(7):748-55. PMC: 3781194. DOI: 10.4161/epi.25178. View

11.

Jones M, Goodman S, Kobor M . DNA methylation and healthy human aging. Aging Cell. 2015; 14(6):924-32. PMC: 4693469. DOI: 10.1111/acel.12349. View

12.

Ashktorab H, Brim H . DNA Methylation and Colorectal Cancer. Curr Colorectal Cancer Rep. 2015; 10(4):425-430. PMC: 4286876. DOI: 10.1007/s11888-014-0245-2. View

13.

Bingham S, Riboli E . Diet and cancer--the European Prospective Investigation into Cancer and Nutrition. Nat Rev Cancer. 2004; 4(3):206-15. DOI: 10.1038/nrc1298. View

14.

Cordero F, Ferrero G, Polidoro S, Fiorito G, Campanella G, Sacerdote C . Differentially methylated microRNAs in prediagnostic samples of subjects who developed breast cancer in the European Prospective Investigation into Nutrition and Cancer (EPIC-Italy) cohort. Carcinogenesis. 2015; 36(10):1144-53. DOI: 10.1093/carcin/bgv102. View

15.

Greenland S . Quantitative methods in the review of epidemiologic literature. Epidemiol Rev. 1987; 9:1-30. DOI: 10.1093/oxfordjournals.epirev.a036298. View

16.

Heiss J, Brenner H . Impact of confounding by leukocyte composition on associations of leukocyte DNA methylation with common risk factors. Epigenomics. 2017; 9(5):659-668. DOI: 10.2217/epi-2016-0154. View

17.

Terry M, Delgado-Cruzata L, Vin-Raviv N, Wu H, Santella R . DNA methylation in white blood cells: association with risk factors in epidemiologic studies. Epigenetics. 2011; 6(7):828-37. PMC: 3154425. DOI: 10.4161/epi.6.7.16500. View

18.

Austin P . Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med. 2009; 28(25):3083-107. PMC: 3472075. DOI: 10.1002/sim.3697. View

19.

Ali R, Marafie M, Bitar M, Al-Dousari F, Ismael S, Bin Haider H . Gender-associated genomic differences in colorectal cancer: clinical insight from feminization of male cancer cells. Int J Mol Sci. 2014; 15(10):17344-65. PMC: 4227166. DOI: 10.3390/ijms151017344. View

20.

Lonning P, Berge E, Bjornslett M, Minsaas L, Chrisanthar R, Hoberg-Vetti H . White Blood Cell BRCA1 Promoter Methylation Status and Ovarian Cancer Risk. Ann Intern Med. 2018; 168(5):326-334. DOI: 10.7326/M17-0101. View