A Functional Single Nucleotide Polymorphism in Mucin 1, at Chromosome 1q22, Determines Susceptibility to Diffuse-Type Gastric Cancer

Saeki, Norihisa; Saito, Akira; Choi, Il Ju; Matsuo, Keitaro; Ohnami, Sumiko; Totsuka, Hirohiko; Chiku, Suenori; Kuchiba, Aya; Lee, Yeon–Su; Yoon, Kyong–Ah; Kook, Myeong–Cherl; Park, Sook Ryun; Kim, Young Woo; Tanaka, Hideo; Tajima, Kazuo; Hara, Hiroshi; Tanioka, Fumihiko; Matsuno, Yoshihiro; Sugimura, Haruhiko; Kato, Shunji; Nakamura, Toshiyasu; Nishina, Tomohiro; Yasui, Wataru; Aoyagi, Kazuhiko; Sasaki, Hiroki; Yanagihara, Kazuyoshi; Katai, Hitoshi; Shimoda, Tadakazu; Yoshida, Teruhiko; Nakamura, Yusuke; Hirohashi, Setsuo; Sanada, Hiromi

doi:10.1053/j.gastro.2010.10.058

Cited by 110 publications

(145 citation statements)

References 35 publications

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“…A following study considered MUC1 a major susceptibility gene and the SNP with MUC1 (rs2070803) was significantly associated with diffuse-type gastric cancer (Sakamoto et al 2008;Saeki et al, 2011). In the present study, we evaluated the association of the two SNPs (rs2294008 in PSCA and rs2070803 in MUC1) with gastric cancer susceptibility in a Chinese population.…”

Section: Research Communicationmentioning

confidence: 97%

Case-control Study of Single Nucleotide Polymorphisms of PSCA and MUC1 Genes with Gastric Cancer in a Chinese

Mei-zuo²,

Li³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Aims: A case-control study of 300 gastric cancer patients and 300 controls was conducted to investigate whether the polymorphisms rs2294008 in PSCA and rs2070803 in MUC1 might be associated with risk of gastric cancer in a Chinese population. Methods: Single nucleotide polymorphisms (SNPs) were genotyped using the Sequenom MassARRAY platform. Results: The data showed that the rs2294008 TT genotype increased gastric cancer risk to an adjusted odds ratio (OR) of 2.26 (95%CI 1.25-4.07), TC to 1.72 (95%CI 1.23-2.42) and TC/TT to 1.81 (95% CI 1.31-2.50), while the rs2070803 GA genotype was associated with a decrease in risk to an adjusted OR of 0.42 (95% CI 0.28-0.62) and rs2070803 GA / AA to 0.46 (95% CI 0.32-0.67). Further stratification analysis revealed that rs2294008 in PSCA consistently increased risk of both intestinal and diffuse-type gastric cancers. The effect of rs2070803 in MUC1 was noteworthily also consistent with both subtypes. Conclusions: 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.

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Section: Research Communicationmentioning

confidence: 97%

Case-control Study of Single Nucleotide Polymorphisms of PSCA and MUC1 Genes with Gastric Cancer in a Chinese

Mei-zuo²,

Li³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…(13) While rs2070803 was one of the original LD mapping markers, which we found to have an association with DGC, we later identified rs4072037 in the MUC1 gene as a functional SNP. (13) In addition, the combined genotype association data of rs2294008 in PSCA and rs4072037 in MUC1, both of which were shown to have biological functions (discussed in sections PSCA gene and MUC1 gene), revealed that 66.5% of the Japanese control subjects had the risk genotype of rs4072037 (risk allele = A, in a recessive model of the allele effect), 84.6% had the risk genotype of rs2294008 (risk allele = T, in a dominant model) and 55.8% had both, showing an odds ratio = 8.4 (Fig. 1).…”

Section: à4mentioning

confidence: 77%

“…(12) The subsequent linkage-disequilibrium (LD) analyses revealed two genes in the LD block at 8q24.3 and five genes at 1q22. (12,13) In the 8q24.3 locus, prostate stem cell antigen (PSCA) gene was identified as a DGC susceptibility gene, with a significant association between DGC and two SNP, rs2976392 and rs2294008, in the gene (rs2976392: 926 cases, 1397 controls, allele-specific odds ratio = 1.71, 95% confidence interval = 1.50 -1.94, P = 1.5 9 10 À16 ; rs2294008: 925 cases, 1396 controls, allele-specific odds ratio = 1.67, 95% confidence interval = 1.47 -1.90, P = 2.2 9 10 À15 ). (12) The association was replicated in 1 To whom correspondence should be addressed.…”

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confidence: 99%

Genetic factors related to gastric cancer susceptibility identified using a genome‐wide association study

et al. 2012

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Gastric cancer (GC) is one of the major malignant diseases worldwide, especially in Asia, where Japan and Korea have the highest incidence in the world. Gastric cancer is classified into intestinal and diffuse types. While the former is almost absolutely caused by Helicobacter pylori infection as the initial insult, the latter seems to include cases in which the role of infection is limited, if any, and a contribution of genetic factors is anticipated. Previously, we performed a genome-wide association study (GWAS) on diffusetype GC by using single nucleotide polymorphisms (SNP) catalogued for Japanese population (JSNP), and identified a prostate stem cell antigen (PSCA) gene encoding a glycosylphosphatidylinositol-anchored cell surface antigen as a GC susceptibility gene. From the second candidate locus identified using the GWAS, 1q22, we found the Mucin 1 (MUC1) gene encoding a cell membranebound mucin protein as another gene related to diffuse-type GC. A two-allele analysis based on risk genotypes of the two genes revealed approximately 95% of Japanese population have at least one of the two risk genotypes, and approximately 56% of the population have both risk genotypes. The two-SNP genotype might offer ample room to further stratify a high GC risk subpopulation in Japan and Asia by adding another genetic and/or non-genetic factor. Recently, a GWAS on the Chinese population disclosed an additional three GC susceptibility loci: 3q13.31, 5p13.1 and 10q23. (Cancer Sci 2013; 104: 1-8) G astric cancer (GC) is one of the major malignant diseases and the second causal of cancer death worldwide.(1) It is usually classified into two types, intestinal and diffuse, a classification which was originally based on histological observation but is recently thought to reflect its pathogenesis.(2) The majority of intestinal-type GC (IGC) arises in the sequence of inflammatory change of the gastric epithelium resulting from bacterial infection; Helicobacter pylori (HP) infectionchronic inflammation -intestinal metaplasia -dysplasia -adenocarcinoma. In contrast, de novo diffuse-type GC (DGC) is thought to emerge in a histologically almost normal epithelium as a consequence of some genetic change that occurred in gastric stem cells and/or epithelial precursor cells, although some cases with DGC might represent dedifferentiated stages of IGC, and a contribution of HP is also suggested.(3) In other words, it is apparent that the pathogenesis of IGC is initiated by HP infection, a class I carcinogen acknowledged by WHO, and therefore IGC is essentially a preventable disease by eradicating HP infection. However, DGC might develop earlier in life than IGC, (4) and no definite DGC-specific environmental risk factor has been established. Therefore, so far we have neither solid strategy nor promising theory to envision a consistent diminution of the incidence of DGC.The incidence of GC has strong geographical and ethnical characteristics. For example, it is one of the rare cancers in North America and Europe, while its incidence is s...

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“…Gastric cancer risk SNPs were extracted from the original gastric cancer GWAS studies in GWAS Catalog 5, 6, 7, 8, 9, 10, 27. Only 1 SNP was remained when multiple variants were in linkage disequilibrium (LD, r 2 ≥ .8), and the minor‐allele frequency (MAF) should be greater or equal than .05.…”

Section: Methodsmentioning

confidence: 99%

“…Many genetic variations, most of which are single nucleotide polymorphisms (SNPs), have been detected over the past years by the genome‐wide association studies (GWAS) of gastric cancer 4. These common susceptibility loci included 1q22 ( MUC1 ), 3q13.32 ( ZBTB20 ), 5p13.1 ( PRKAA1 ), 5q14.3 ( lnc‐POLR3G‐4 ), 6p21.1 ( UNC5CL ), 8q24 ( PSCA ), and 10q23 ( PLCE1 ) 5, 6, 7, 8, 9, 10…”

Section: Introductionmentioning

confidence: 99%

Germline genetic variants were interactively associated with somatic alterations in gastric cancer

et al. 2018

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Genome‐wide association studies have identified several germline variants in gastric cancer. Meanwhile, sequencing studies have characterized extensive somatic alterations that arise during gastric carcinogenesis. However, the relationship between the germline variants and somatic alterations is still unclear in gastric cancer. A total of 11 susceptibility loci and 276 driver genes of gastric cancer were determined based on previous studies and publicly available database. An enrichment analysis was made to detect whether driver genes were enriched in susceptibility regions. Besides, we performed a pathway enrichment analysis to find common‐enrich pathways of cancer driver genes and susceptibility genes. Finally, on the basis of the gastric cancer samples and data from TCGA STAD project, we evaluated the associations between susceptibility loci and somatic alterations. Enrichment analysis showed that gastric cancer susceptibility genes were more likely to be enriched in driver genes than in all the genes (P = .05). The susceptibility genes and driver genes were commonly enriched in 8 biological pathways. Gastric cancer susceptibility locus of rs2285947 was associated with truncation mutation within Signaling by PDGF pathway (OR = 0.26, 95%CI: 0.12‐0.55, P = 3.93 × 10−4). The rs1679709 was connected with COSMIC Signature15 (P = .026). Moreover, rs1679709 was also associated with copy number values of RFC4 which is related to Signature15. These results provide evidence for the relationship between germline variants and somatic alterations, which facilitate understanding the interactive mechanism of germline variations with somatic alterations in gastric cancer development.

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A Functional Single Nucleotide Polymorphism in Mucin 1, at Chromosome 1q22, Determines Susceptibility to Diffuse-Type Gastric Cancer

Cited by 110 publications

References 35 publications

Case-control Study of Single Nucleotide Polymorphisms of PSCA and MUC1 Genes with Gastric Cancer in a Chinese

Case-control Study of Single Nucleotide Polymorphisms of PSCA and MUC1 Genes with Gastric Cancer in a Chinese

Genetic factors related to gastric cancer susceptibility identified using a genome‐wide association study

Germline genetic variants were interactively associated with somatic alterations in gastric cancer

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