Abstract
Gastric cancer (GC) is one of the major malignant diseases worldwide, especially in Asia. It is classified into intestinal and diffuse types. While the intestinal-type GC (IGC) is almost certainly caused by Helicobacter pylori (HP) infection, its role in the diffuse-type GC (DGC) appears limited. 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. MUC1 has been known as an oncogene with an anti-apoptotic function in cancer cells; however, in normal gastric mucosa, it is anticipated that the mucin 1 protein has a role in protecting gastric epithelial cells from a variety of external insults which cause inflammation and carcinogenesis. HP infection is the most definite insult leading to GC, and a protective function of mucin 1 protein has been suggested by studies on Muc1 knocked-out mice.
Highlights
Gastric cancer (GC) is one of the major cancers and the second most deadly form of cancer worldwide [1]
These findings suggest that rs4072037 influences the quantity and/or the quality of the mucin 1 gene (MUC1) protein, which causes a difference in its barrier function in the stomach and subsequently the difference in GC susceptibility between individuals
Contrary to its protective function in normal gastric epithelial cells, the two findings mentioned above suggest a different function of MUC1 in GC cells: the gene is silenced in intestinal metaplasia, a pre-neoplastic lesion, but frequently reactivated in GC, and its expression is correlated to poor prognosis
Summary
Gastric cancer (GC) is one of the major cancers and the second most deadly form of cancer worldwide [1]. The geographical enigma suggests that genetic factors may contribute to IGC development With this as a background, three genome-wide association studies (GWASes) were recently performed for detecting the genetic factors related to GC susceptibility, and two of them identified chromosome 1q22 harboring the mucin 1 (MUC1) gene as a GC susceptibility locus [8,9,10,11]. DNA samples are digested with restriction enzymes It was demonstrated in a Caucasian population (159 GC cases and 324 controls) that SS genotypes of MUC1 had an increased risk of developing GC (SS to LL, OR = 4.3, 95% CI = 1.8–10.5, p < 0.0001) [36], and the two alleles, the S and the A of rs4072037, as well as the L and the G of the SNP are in LD, respectively, in Japanese and European populations [9,29].
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