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Polymorphisms in the CLDN1 and CLDN7 genes are related to differentiation and tumor stage in colon carcinoma
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Section for Pathology, Örebro University Hospital, Örebro, Sweden.
Department of Laboratory Medicine, Section for Pathology, Örebro University Hospital, Örebro, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Section for Pathology, Örebro University Hospital, Örebro, Sweden.
Örebro University Hospital. Department of Clinical Surgery.
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2014 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 7, 636-642 p.Article in journal (Refereed) Published
Abstract [en]

Tight junction is composed of transmembrane proteins important for maintaining cell polarity and regulating ion flow. Among these proteins are the tissue-specific claudins, proteins that have recently been suggested as tumor markers for several different types of cancer. An altered claudin expression has been observed in colon, prostatic, ovarian, and breast carcinoma. The aim of this study was to analyze the allele frequencies of three common single nucleotide polymorphisms (SNPs) in the genes for claudin 1 and claudin 7 in colon cancer (CC) patients and in a control population of healthy blood donors. Pyrosequencing was used to genotype the CLDN1 SNP rs9869263 (c.369C>T), and the CLDN7 SNPs rs4562 (c.590C>T) and rs374400 (c.606T>G) in DNA from 102 formalin fixed paraffin embedded (FFPE) colon cancer tissue, and 111 blood leukocyte DNA from blood/plasma donors. These results were correlated with clinical parameters such as TNM stage, tumor localization, tumor differentiation, complexity index, sex, and age. We found that there was a significant association between the CLDN1 genotype CC in tumor samples and a higher risk of colon cancer development (OR 3.0, p < 0.001). We also found that the CLDN7 rs4562 (c.590C>T) genotype CT had a higher risk of lymph node involvement (p = 0.031) and a lower degree of tumor differentiation (p = 0.028). In the control population, the allele frequencies were very similar to those in the HapMap cohort for CLDN7. The CLDN1 rs9869263 genotype (c.369C>T) was related to increased risk of colon cancer, and the CLDN7 rs4562 genotype (c.590C>T) was related to tumor differentiation and lymph node involvement in colon carcinoma. Further studies are warranted to ascertain their potential uses as biomarkers predicting tumor development, proliferation, and outcome in this disease.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2014. Vol. 122, no 7, 636-642 p.
Keyword [en]
Tight junction, SNP, colon cancer, claudin
National Category
Immunology in the medical area Microbiology in the medical area
Identifiers
URN: urn:nbn:se:oru:diva-35806DOI: 10.1111/apm.12211ISI: 000338030400009PubMedID: 24479816Scopus ID: 2-s2.0-84902835219OAI: oai:DiVA.org:oru-35806DiVA: diva2:741492
Note

Funding Agencies:

Nyckelfonden, Örebro University Hospital, Örebro, Sweden

Lions cancer research foundation, Uppsala, Sweden

Available from: 2014-08-28 Created: 2014-07-30 Last updated: 2017-10-18Bibliographically approved

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Hahn-Strömberg, VictoriaBefekadu, RahelMatthiessen, PeterKarlsson, Sune
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School of Health and Medical Sciences, Örebro University, SwedenÖrebro University HospitalÖrebro University School of Business
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Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS)
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CiteExportLink to record
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