Abstract
BackgroundThe single-nucleotide polymorphism SLC39A6 rs1050631 is strongly implicated in esophageal squamous cell carcinoma, leading us to question whether it may also play a role in gastric adenocarcima (GA).MethodsWe genotyped the SLC39A6 rs1050631 in 512 patients who underwent GA resection. All study subjects lived in an area of China with high GA incidence. Genotypes were examined for possible correlation with survival and recurrence. The potential involvement of SLC39A6 in gastric cancer was explored in clinical samples and cell culture studies.ResultsMultivariable analysis showed that patients with the CT + TT genotype at SLC39A6 rs1050631 were at greater risk of recurrence (hazard ratio, HR 1.387, p = 0.004) and death (HR 1.429, p = 0.002) than patients with CC genotype. Median recurrence-free and overall survival were significantly shorter in patients with the CT + TT genotype (20, 27 months) than in patients with the CC genotype (36, 43 months, p = 0.001, p < 0.001). Patients with the CT + TT genotype who were male or ≥ 60 years, or who had a tumor ≥5 cm or a moderately differentiated tumor were at significantly higher risk of recurrence and death. SLC39A6 was overexpressed in tissues from GA patients and in GA cell lines, and SLC39A6 knockdown in GA cell lines inhibited their proliferation, migration and invasion.ConclusionSLC39A6 rs1050631 correlates with post-resection prognosis of GA patients and SLC39A6 may participate in GA onset or progression.
Highlights
The single-nucleotide polymorphism SLC39A6 rs1050631 is strongly implicated in esophageal squamous cell carcinoma, leading us to question whether it may play a role in gastric adenocarcima (GA)
We decided to focus on this polymorphism, other polymorphisms may be important in gastric cancer.All patients were diagnosed with primary GA
Multivariable analysis showed that patients with the CT genotype were at increased recurrence risk if they were male (HR 1.564, p = 0.001), aged ≥60 years (HR 1.512, p = 0.009), with a tumor ≥5 cm (HR 1.807, p = 0.001) or with a moderately differentiated tumor (HR 1.830, p < 0.001) than those patients with CC genotype had (Additional file 1: Table S1)
Summary
The single-nucleotide polymorphism SLC39A6 rs1050631 is strongly implicated in esophageal squamous cell carcinoma, leading us to question whether it may play a role in gastric adenocarcima (GA). Most gastric cancer cases occur in Asia, in China [2, 3]. The incidence of gastric cancer, its progression and patient prognosis differ across geographic regions and ethnic groups, and the reasons for these variations are poorly understood. Gao et al BMC Cancer (2019) 19:1069. We obtained clinical samples from patients in Fujian province following resection to treat GA, and examined potential association between SLC39A6 r1050631 with clinical outcomes. We examined the relationship between SLC39A6 expression and SLC39A6 r1050631. Potential effects of knocking down SLC39A6 expression were examined in representative GA cell lines
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