Abstract
FOSL1 (FOS like antigen 1) is one kind of proto-oncogene, and may play a vital role in carcinogenesis of multiple cancers. However, studies about the relationship between SNPs in FOSL1 and gastric cancer are still lacking. Thus, we investigated the association of seven SNPs in FOSL1 with gastric cancer using case-control design in a two-stage strategy (Screening stage: 1,140 gastric cancer cases and 1,547 controls; Replication stage: 1,006 cases and 2,273 controls). We found that rs1892901 was significantly associated with increased risk of gastric cancer in additive model (adjusted OR = 1.25, 95%CI: 1.06–1.47, P = 0.008) in first stage. Following replication results revealed that the relationship between rs1892901 and gastric cancer risk was consistent with our primary results. In silico analysis showed that rs1892901 might alter multiple regulatory motifs, disturb protein binding, and affect the expression of FOSL1 and other important gastric cancer-related genes such as EGR1, CHD, EP300, FOS, JUN and FOSL2. Our findings indicated that functional SNP rs1892901 in FOSL1 might affect the expression of FOSL1, and ultimately increase the risk of gastric cancer. Further functional studies and large-scale population studies are warranted to confirm our findings.
Highlights
The incidence and mortality of gastric cancer have been steadily decreasing in the past decades throughout the world, especially in the developed countries[1,2]
We systematically evaluated the relationships of tagging SNPs in FOS like antigen 1 (FOSL1) gene with gastric cancer risk in a two-stage case-control study in Chinese (Screening stage and Replication stage)
It has been reported that both Fos family and JUN family could function as oncogenic transcription factors[18], while the increased expression of FOSL1 might be more predictive of oncogenic activity[19]
Summary
The incidence and mortality of gastric cancer have been steadily decreasing in the past decades throughout the world, especially in the developed countries[1,2]. FOS like antigen 1 (FOSL1) is a member of the Fos gene family that plays important roles in cell proliferation, differentiation, transformation and metastasis[5,6]. FOSL1 may influence the occurrence and development of multiple types of cancers including gastric cancer. There are limited studies focusing on the relationship of genetic variants in FOSL1 with gastric cancer. We hypothesized that the SNPs in FOSL1 gene might play an important role in the carcinogenesis and progression of gastric cancer. We investigated the association of seven SNPs in FOSL1 gene with gastric cancer in a two-stage case-control study in Chinese (Screening stage: 1,140 gastric cancer cases and 1,547 controls; Replication stage: 1,006 cases and 2,273 controls)
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