Abstract
PurposeRecently, genetic polymorphism (rs3803662C>T) in TOX3 was reported to induce the risk of breast cancer. In this study, we hypothesized that rs3803662 could influence gastric cancer survival outcomes.MethodsWith multiplex SNaPshot method, we genotyped TOX3 rs3803662 in 880 gastric patients with surgical resection. The association between genotype and survival outcomes was performed by the Kaplan-Meier method, Cox regression analysis models and the log-rank test.ResultsThere was no association in the analyses of rs3803662 and survival of gastric cancer. However, the stratified analysis by histology showed that rs3803662 CT/TT genotype was associated with a significantly better survival for diffuse-type gastric cancer (log-rank p = 0.030, hazard ratio [HR] = 0.67, 95% confidence interval [CI] = 0.46–0.96), than the CC genotype. In addition, this favorable effect was especially obvious among gastric cancer patients with tumor size >5 cm, T3 and T4 depth of invasion, lymph node metastasis, no drinking, no distant metastasis, no chemotherapy and gastric cardia cancer.Conclusions TOX3 rs3803662 might play an important role in the prognostic outcome and treatment of gastric cancer, especially perhaps further help in explaining the reduced risk of death associated with diffuse-type gastric cancer.
Highlights
Gastric cancer is the fourth common type of malignant tumor in the world and the leading cause of cancer deaths in China, Japan and Eastern European countries [1]
Extensive epidemiological studies have demonstrated that genetic variants, single nucleotide polymorphisms (SNPs), are likely to modulate the effect of environmental risk factors through modifying functions of various biological pathways involved in gastric carcinogenesis in response to environmental exposure
Several common low-penetrant genes have been identified as potential gastric cancer susceptibility genetic variants, such as Glutathione S-transferase M1 (GSTM1) polymorphism
Summary
Gastric cancer is the fourth common type of malignant tumor in the world and the leading cause of cancer deaths in China, Japan and Eastern European countries [1]. Survival in patients with advanced gastric cancer remains poor. Extensive epidemiological studies have demonstrated that genetic variants, single nucleotide polymorphisms (SNPs), are likely to modulate the effect of environmental risk factors through modifying functions of various biological pathways involved in gastric carcinogenesis in response to environmental exposure. Several common low-penetrant genes have been identified as potential gastric cancer susceptibility genetic variants, such as Glutathione S-transferase M1 (GSTM1) polymorphism. It has been found genetic variant may be a useful marker for predicting the prognosis of patients with gastric cancer. Previous studies reported PSCA rs2294008 and APE1 rs1760944 are associated with gastric cancer survival [5,6]
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