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

Abstract

<b>Background:</b> Aberrant DNA methylation, especially tumor suppressor gene hypermethylation, is a well-recognized biomarker of initial tumorogenesis stages. <i>FAT4</i> and <i>SOX11</i> 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. <b>Methods:</b> 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 <i>FAT4</i> and <i>SOX11</i> methylation with GC susceptibility. <b>Results:</b> Positive methylation (Pm) and total positive methylation (Tpm) of <i>FAT4</i> were significantly increased the risk of GC (OR = 2.204, 95% CI: 1.168-4.159, <i>P</i> = 0.015; OR = 1.583, 95% CI: 1.031-2.430, <i>P</i> = 0.036, respectively). Compared with controls, cases exhibited higher <i>SOX11</i> Pm frequencies with OR of 2.530 (95% CI: 1.289-4.969, <i>P</i> = 0.007). Nonetheless, no statistically significant association between <i>SOX11</i> Tpm and GC risk was observed. Additionally, interactions between <i>FAT4</i> 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, <i>P</i> = 0.009), and high salt intake interacted with <i>SOX11</i> Tpm also showed statistically significant (OR = 0.490, 95% CI: 0.242-0.995, <i>P</i> = 0.048). <b>Conclusions:</b><i>FAT4</i> aberrant methylation in peripheral blood leukocytes and gene-environment interactions were associated with the risk of GC, while <i>SOX11</i> was controversial and needed to be more investigated.