Mo1131 Genetic Polymorphism of MAFK (Rs4268033) Is Associated With the Susceptibility to Gastric Cancer in Japan

Abstract

[Background] The small Maf proteins have emerged as crucial regulators of mammalian gene expression. Small Mafs do not contain an obvious transcriptional activation domain. However, it has been clear that small Maf proteins are regulated transcription factors, such as Nrf2 or Bach1. MafK, one of the small Maf proteins, is encoded by MAFK gene. Within 20kbp around MAFK gene, there are two linkage disequilibrium blocks, with above 0.05 of HWE p value and above 0.05 of minor allele frequency. In this study, we investigated an association between gastric cancer (UC) and each tag polymorphism, rs4268033G .A and rs3735656 (*910T.C), and the other one rs10226620 (*1506T.C). [Material and Methods] The study was performed in 334 patients with gastric cancer (GC cases) and 661 subjects with no evidence of gastric malignancies (controls) on upper gastro-duodenal endoscopy. We employed the PCR-SSCP method to detect the gene polymorphism. [Results] The mean age, male/female ratio and Helicobacter pylori (HP) positive ratio in GC cases were significantly higher than those in controls. The distributions of rs4268033, rs3735656 and rs10226620 in controls were 326GG, 284GA and 51AA (HWE p=0.35), 291TT, 304TC and 66CC (HWE p=0.33) and 304TT, 288TC and 69CC (HWE p=0.93) respectively, whereas the distributions in GC cases was 127GG, 163GA and 44AA, 142TT, 153TC and 39CC, 144TT, 154TC and 36CC, respectively. The allelic frequency of rs4268033 Awas significantly higher in GC cases than in controls ‘(37.6% vs. 29.2%, p=0.0002). Overall, rs4268033 minor variant had a significantly increased risk for the development of gastric cancer by logistic regression analysis after adjustment for gender, age and HP infection status (recessive genetic model: OR, 1.72 95%CI, 1.10-2.69; p=0.016 and dominant genetic model: OR, 1.61; 95%CI, 1.21-2.14; p=0.0009), whereas no significant association was found between gastric cancer susceptibility and rs3735656 or rs10226620. The rs4268033 minor allele was more strongly associated with intestinal type of gastric cancer (recessive genetic model: OR, 2.12; 95%CI, 1.27-3.54; p=0.0040 and dominant genetic model: OR, 1.66; 95%CI, 1.17-2.35; p=0.0042), and slightly associated with diffuse type of gastric cancer (dominant genetic model: OR, 1.50; 95%CI, 1.02-2.21; p=0.040). In addition, rs4268033 minor allele was significantly associated with non-cardiac gastric cancer (recessive genetic model: OR, 1.76; 95%CI, 1.11-2.77; p=0.015 and dominant genetic model: OR, 1.68; 95%CI, 1.252.25; p=0.0005). [Conclusion] Our results provided the first evidence that MAFK gene polymorphism is significantly associated with the susceptibility to gastric cancer development. The rs4268033 minor allele is closely associated with an increased risk for the development of gastric cancer.