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Investigating the association between polymorphisms in connective tissue growth factor and susceptibility to colon carcinoma
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Department of Clinical Medicine, Örebro University, Örebro, Sweden.
Örebro University Hospital. Department of Laboratory Medicine, Section for Transfusion Medicine.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
2015 (English)In: Molecular Medicine Reports, ISSN 1791-2997, E-ISSN 1791-3004, Vol. 11, no 4, 2493-2503 p.Article in journal (Refereed) Published
Abstract [en]

There have been numerous studies on the gene expression of connective tissue growth factor (CTGF) in colorectal cancer, however very few have investigated polymorphisms in this gene. The present study aimed to determine whether single nucleotide polymorphisms (SNPs) in the CTGF gene are associated with a higher susceptibility to colon cancer and/or an invasive tumor growth pattern. The CTGF gene was genotyped for seven SNPs (rs6918698, rs1931002, rs9493150, rs12526196, rs12527705, rs9399005 and rs12527379) by pyrosequencing. Formalin-fixed paraffin-embedded tissue samples (n=112) from patients diagnosed with colon carcinoma, and an equal number of blood samples from healthy controls, were selected for genomic DNA extraction. The complexity index was measured using images of tumor samples (n=64) stained for cytokeratin-8. The images were analyzed and correlated with the identified CTGF SNPs and clinicopathological parameters of the patients, including age, gender, tumor penetration, lymph node metastasis, systemic metastasis, differentiation and localization of tumor. It was demonstrated that the frequency of the SNP rs6918698 GG genotype was significantly associated (P=0.05) with an increased risk of colon cancer, as compared with the GC and CC genotypes. The other six SNPs (rs1931002, rs9493150, rs12526196, rs12527705, rs9399005 and rs12527379) exhibited no significant difference in the genotype and allele frequencies between patients diagnosed with colon carcinoma and the normal healthy population. A trend was observed between genotype variation at rs6918698 and the complexity index (P=0.052). The complexity index and genotypes for any of the studied SNPs were not significantly correlated with clinical or pathological parameters of the patients. These results indicate that the rs6918698 GG genotype is associated with an increased risk of developing colon carcinoma, and genetic variations at the rs6918698 are associated with the growth pattern of the tumor. The present results may facilitate the identification of potential biomarkers of the disease in addition to drug targets.

Place, publisher, year, edition, pages
Spandidos Publications , 2015. Vol. 11, no 4, 2493-2503 p.
Keyword [en]
Clinicopathological parameters; Genotyping; Pyrosequencing
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:oru:diva-44430DOI: 10.3892/mmr.2014.3083ISI: 000351711100018PubMedID: 25502877Scopus ID: 2-s2.0-84921364673OAI: oai:DiVA.org:oru-44430DiVA: diva2:807687
Note

Funding Agencies:

Lions Cancer Research Foundation (Uppsala, Sweden)

Örebro University Hospital Research Council

Nyckelfonden, Örebro University Hospital (Örebro, Sweden)

Available from: 2015-04-24 Created: 2015-04-24 Last updated: 2017-10-18Bibliographically approved

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