However, subtype-specific associations were observed for gastric cardia adenocarcinomas at MUC1/TRIM46/1q22 rs2070803 [HRAA versus GA+GG = 2.16; 95% confidence interval (CI) = 1.24-3.78; P = 0.0068] and LTA/TNF/6p21.33 rs1799724 (HRTT+CT versus CC = 1.30; 95% CI = 1.07-1.57; P = 0.0077), and for diffuse-type GC at PSCA/8q24.3 rs2294008 (HRTT versus CT+CC = 1.99; 95% CI = 1.33-2.97; P = 7.8E-04).
In conclusion, this meta-analysis suggested that rs4245739 polymorphism in the MUC1 gene may play a pivotal role in the pathogenesis of GC, especially for white populations.
We also confirmed a previously reported association for rs4072037 in MUC1 with p=6.59×10(-8) for total gastric cancer and similar estimates for cardia and non-cardia cancers.
Our results confirm an association between gastric cancer in Europeans and three loci previously reported in Asians, MUC1, PRKAA1 and PSCA, refine the association signal at PRKAA1 and support a pathogenic role for the tandem repeat identified in MUC1.
The aim of this study was to determine whether rs4072037A > G in MUC1 at 1q22 and rs2274223A > G in PLCE1 at 10q23 are associated with a risk of gastric cancer in a Korean population.
Recently, genome-wide association studies (GWAS) on Japanese and Chinese populations identified chromosome 1q22 as a GC susceptibility locus which harbors mucin 1 gene (MUC1) encoding a cell membrane-bound mucin protein.
In conclusion, MUC1rs4072037 polymorphism may be used as potential biomarker for cancer susceptibility particularly for gastric cancer and for Asian population.
Overall, our data indicated that common genetic variations in MUC1 gene might not make a major contribution to the risk of H. pylori infection and non-cardia gastric cancer in our studied population.
In this two-stage study, we selected 24 putative functional tag single-nucleotide polymorphisms (tagSNPs) for six H.pylori-related host genes, MUC1, toll-like receptor 4 (TLR4), protein tyrosine phosphatase, non-receptor type 11 (PTPN11), IL-1B, PGC and PGA3-5, and analyzed their influence and interaction with H.pylori on the GA and GC risks.
From the second candidate locus identified using the GWAS, 1q22, we found the Mucin 1 (MUC1) gene encoding a cell membrane-bound mucin protein as another gene related to diffuse-type GC.
Our study suggested rs2294008 in the PSCA gene to be associated with increased risk of gastric cancer and rs2070803 in MUC1 to play a protective role in a Chinese population.
The rs4072037 polymorphism in MUC1 was associated with a reduced risk of GC of intestinal histological type (OR 0.4; 95% CI 0.2-0.9) and a reduced risk of oesophageal squamous cell cancer (OR 0.5; 95% CI 0.2-1.0), but not oesphageal adenocarcinoma.
Thus we have provided evidence that may identify the MUC1 A/G polymorphism at 568 site, as a potential genetic factor which leads to an increase in susceptibility for GC through alteration of MUC1 gene and MUC1 expression in the population that carry the A allele.
These findings indicate that MUC1 CT plays a role in the intracellular signaling through its interaction with beta-catenin and upregulate the Wnt target gene cyclinD1 in CagA H. pylori-infected gastric carcinoma.
Both CEA and MUC1 mRNA expression was correlated significantly with all malignant biological properties of GC, such as macroscopic type, depth of tumor invasion, lymph-node metastasis, TNM stage and coexisting distant metastasis (all p < 0.05).