HFE gene expressions and polymorphisms in gastric cancers: A pilot study

Abstract

Background: GC has a poor prognosis and causes a significant global health burden, being the fourth cause of cancer mortality worldwide. The HFE gene polymorphisms H63D and C282Y have been linked to various cancers, but its pathogenic role in gastric cancers (GC) is not studied in detail. Therefore, further experimentation on HFE gene variants and GC is necessary to confirm the hypothesis that iron overload induces tumourigenesis.

Aims: The overall aim of this study is to identify if GC risk is associated with HFE gene expressions and polymorphisms with relation to cytotoxic iron overload.

Methods: A retrospective case-control study was conducted on 20 patient samples with GC tissues and matched normal gastric tissues, collected from patients who underwent diagnostic stomach endoscopies or gastrostomies at Kaohsiung Medical University, Taiwan. For gene expression analysis, a quantitative polymerase chain reaction (qPCR) was performed to investigate HFE gene expression levels in the 20 GC tissues and matched normal gastric tissues. The H63D and C282Y polymorphisms were detected through Sanger sequencing.

Results: An up-regulation of HFE mRNA expression levels was noted in ∼35% (7/20) of GC patients, whereas ∼65% (13/20) showed low HFE expression. Furthermore, through current Sanger sequencing analysis, neither any C282Y polymorphisms nor any H63D polymorphisms have been identified. Nonetheless, one sample has a HFE variant known as rs369354634 (c.843G>A), and another variant (c.184G>A) has also been found in five samples.

Conclusion: This pilot study has confirmed varied expression profiling for HFE gene expressions in GCs, and it may have potential association with gene polymorphisms. However, larger sample size and additional data are required to support the hypothesis and confirm significance.