Association of MUC6-minisatellite variants with susceptibility to rectal carcinoma

Ahn, Myoung-Hyun; Bae, Ki Beom; Kwon, Jeong-Ah; Choi, Hong-Jo; Lee, Se-Ra; Kim, Si-Hoon; Jung, Tae Doo; Kim, Sun Hee; An, Min Sung; Hong, Kwan Hee; Heo, Jeonghoon; Kang, Tae-Hong; Chung, Jin Woong; Leem, Sun‐Hee

doi:10.1007/s11033-012-2062-5

Cited by 6 publications

(5 citation statements)

References 21 publications

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“…Given the important role of the mucous barrier in maintaining the gut homeostasis, it is surprising that only four studies have been published regarding potential associations between genetic variants in the mucin genes and CRC [25, 40–42]. Similarly, studies on polymorphisms in mucin genes or on alterations in mucin expression affecting risk of inflammatory bowel diseases are sparse and inconclusive[43].…”

Section: Discussionmentioning

confidence: 99%

Single nucleotide polymorphisms within MUC4 are associated with colorectal cancer survival

et al. 2019

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Mucins and their glycosylation have been suggested to play an important role in colorectal carcinogenesis. We examined potentially functional genetic variants in the mucin genes or genes involved in their glycosylation with respect to colorectal cancer (CRC) risk and clinical outcome. We genotyped 23 single nucleotide polymorphisms (SNPs) covering 123 SNPs through pairwise linkage disequilibrium (r 2 >0.80) in the MUC1 , MUC2 , MUC4 , MUC5AC , MUC6 , and B3GNT6 genes in a hospital-based case-control study of 1532 CRC cases and 1108 healthy controls from the Czech Republic. We also analyzed these SNPs in relation to overall survival and event-free survival in a subgroup of 672 patients. Among patients without distant metastasis at the time of diagnosis, two MUC4 SNPs, rs3107764 and rs842225, showed association with overall survival (HR 1.40, 95%CI 1.08–1.82, additive model, log-rank p = 0.004 and HR 0.64, 95%CI 0.42–0.99, recessive model, log-rank p = 0.01, respectively) and event-free survival (HR 1.31, 95%CI 1.03–1.68, log-rank p = 0.004 and HR 0.64, 95%CI 0.42–0.96, log-rank p = 0.006, respectively) after adjustment for age, sex and TNM stage. Our data suggest that genetic variation especially in the transmembrane mucin gene MUC4 may play a role in the survival of CRC and further studies are warranted.

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Section: Discussionmentioning

confidence: 99%

Single nucleotide polymorphisms within MUC4 are associated with colorectal cancer survival

et al. 2019

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“…MUC6 is expressed preferentially in epithelial tissues, particularly in the gastrointestinal tract ( 68 , 70–73 ). Hence, a major focus in prior work has been on how the MUC6 VNTR polymorphism is associated with risk for gastrointestinal diseases—ulcers, gut infections, and stomach or intestinal cancers ( 60 , 61 , 74–78 ). However, this unique tandem repeat region may have broader impact.…”

Section: Discussionmentioning

confidence: 99%

Alzheimer Disease Pathology-Associated Polymorphism in a Complex Variable Number of Tandem Repeat Region Within the MUC6 Gene, Near the AP2A2 Gene

Katsumata¹,

Fardo²,

Bachstetter³

et al. 2019

Journal of Neuropathology &Amp; Experimental Neurology

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We found evidence of late-onset Alzheimer disease (LOAD)-associated genetic polymorphism within an exon of Mucin 6 (MUC6) and immediately downstream from another gene: Adaptor Related Protein Complex 2 Subunit Alpha 2 (AP2A2). PCR analyses on genomic DNA samples confirmed that the size of the MUC6 variable number tandem repeat (VNTR) region was highly polymorphic. In a cohort of autopsied subjects with quantitative digital pathology data (n = 119), the size of the polymorphic region was associated with the severity of pTau pathology in neocortex. In a separate replication cohort of autopsied subjects (n = 173), more pTau pathology was again observed in subjects with longer VNTR regions (p = 0.031). Unlike MUC6, AP2A2 is highly expressed in human brain. AP2A2 expression was lower in a subset analysis of brain samples from persons with longer versus shorter VNTR regions (p = 0.014 normalizing with AP2B1 expression). Double-label immunofluorescence studies showed that AP2A2 protein often colocalized with neurofibrillary tangles in LOAD but was not colocalized with pTau proteinopathy in progressive supranuclear palsy, or with TDP-43 proteinopathy. In summary, polymorphism in a repeat-rich region near AP2A2 was associated with neocortical pTau proteinopathy (because of the unique repeats, prior genome-wide association studies were probably unable to detect this association), and AP2A2 was often colocalized with neurofibrillary tangles in LOAD.

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“… 12 Other studies on genetic susceptibility due to specific minisatellites have also been reported. 17 , 29 , 30 , 31 …”

Section: Discussionmentioning

confidence: 99%

A polymorphic minisatellite region of BORIS regulates gene expression and its rare variants correlate with lung cancer susceptibility

et al. 2016

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Aberrant expression of BORIS/CTCFL (Brother of the Regulator of Imprinted Sites/CTCF-like protein) is reported in different malignancies. In this study, we characterized the entire promoter region of BORIS/CTCFL, including the CpG islands, to assess the relationship between BORIS expression and lung cancer. To simplify the construction of luciferase reporter cassettes with various-sized portions of the upstream region, genomic copies of BORIS were isolated using TAR cloning technology. We analyzed three promoter blocks: the GATA/CCAAT box, the CpG islands and the minisatellite region BORIS-MS2. Polymorphic minisatellite sequences were isolated from genomic DNA prepared from the blood of controls and cases. Of the three promoter blocks, the GATA/CCAAT box was determined to be a critical element of the core promoter, while the CpG islands and the BORIS-MS2 minisatellite region were found to act as regulators. Interestingly, the polymorphic minisatellite region BORIS-MS2 was identified as a negative regulator that repressed the expression levels of luciferase reporter cassettes less effectively in cancer cells compared with normal cells. We also examined the association between the size of BORIS-MS2 and lung cancer in a case–control study with 590 controls and 206 lung cancer cases. Rare alleles of BORIS-MS2 were associated with a statistically significantly increased risk of lung cancer (odds ratio, 2.04; 95% confidence interval, 1.02–4.08; and P=0.039). To conclude, our data provide information on the organization of the BORIS promoter region and gene regulation in normal and cancer cells. In addition, we propose that specific alleles of the BORIS-MS2 region could be used to identify the risk for lung cancer.

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Association of MUC6-minisatellite variants with susceptibility to rectal carcinoma

Cited by 6 publications

References 21 publications

Single nucleotide polymorphisms within MUC4 are associated with colorectal cancer survival

Single nucleotide polymorphisms within MUC4 are associated with colorectal cancer survival

Alzheimer Disease Pathology-Associated Polymorphism in a Complex Variable Number of Tandem Repeat Region Within the MUC6 Gene, Near the AP2A2 Gene

A polymorphic minisatellite region of BORIS regulates gene expression and its rare variants correlate with lung cancer susceptibility

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