J Cancer 2018; 9(13):2275-2283. doi:10.7150/jca.24797

Research Paper

Aberrant methylation of FAT4 and SOX11 in peripheral blood leukocytes and their association with gastric cancer risk

Hongxu Sun1*, Haibo Zhou1*, Yan Zhang1, Jie Chen1, Xu Han1, Di Huang1, Xiyun Ren1, Yunhe Jia2, Qing Fan3, Wenjing Tian1✉, Yashuang Zhao1✉

1. Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, P. R. China.
2. Department of Colorectal Cancer Surgery, The third affiliated hospital, Harbin Medical University, Harbin, Heilongjiang Province, P. R. China.
3. Xiangfang Center for Disease Control and Prevention, Harbin 150081, Heilongjiang Province, P. R. China.
* These authors contributed equally to this work

Abstract

Background: Aberrant DNA methylation, especially tumor suppressor gene hypermethylation, is a well-recognized biomarker of initial tumorogenesis stages. FAT4 and SOX11 are putative tumor suppressor genes and can be down-regulated by hypermethylation in various cancers tissues. However, in peripheral blood leukocytes, the association between these two genes methylation status, as well as the effects of gene-environment interactions, and gastric cancer (GC) risk remain unclear.

Methods: A hospital-based case-control study including 375 cases and 394 controls was conducted. Peripheral blood leukocytes DNA methylation status were detected by methylation-sensitive high-resolution melting (MS-HRM) assay. Logistic regression was adopted to analyze the relationship of FAT4 and SOX11 methylation with GC susceptibility.

Results: Positive methylation (Pm) and total positive methylation (Tpm) of FAT4 were significantly increased the risk of GC (OR = 2.204, 95% CI: 1.168-4.159, P = 0.015; OR = 1.583, 95% CI: 1.031-2.430, P = 0.036, respectively). Compared with controls, cases exhibited higher SOX11 Pm frequencies with OR of 2.530 (95% CI: 1.289-4.969, P = 0.007). Nonetheless, no statistically significant association between SOX11 Tpm and GC risk was observed. Additionally, interactions between FAT4 Tpm and increased consumption of freshwater fish (≥1 times/week) displayed an antagonistic effect on GC (OR = 0.328, 95% CI: 0.142-0.762, P = 0.009), and high salt intake interacted with SOX11 Tpm also showed statistically significant (OR = 0.490, 95% CI: 0.242-0.995, P = 0.048).

Conclusions: FAT4 aberrant methylation in peripheral blood leukocytes and gene-environment interactions were associated with the risk of GC, while SOX11 was controversial and needed to be more investigated.

Keywords: DNA methylation, peripheral blood leukocytes, gastric cancer, gene-environment interaction.

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How to cite this article:
Sun H, Zhou H, Zhang Y, Chen J, Han X, Huang D, Ren X, Jia Y, Fan Q, Tian W, Zhao Y. Aberrant methylation of FAT4 and SOX11 in peripheral blood leukocytes and their association with gastric cancer risk. J Cancer 2018; 9(13):2275-2283. doi:10.7150/jca.24797. Available from http://www.jcancer.org/v09p2275.htm