Protein expression and genetic variation of IL32 and association with colorectal cancer in Swedish patients
2018 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 38, no 1, p. 321-328Article in journal (Refereed) Published
Abstract [en]
Background: Interleukin 32 (IL32) is an intracellular pluripotent cytokine produced by epithelial cells, monocytes, T-lymphocytes and natural killer cells and seems to be involved in the pathogenesis of cancer and inflammatory diseases. Our purpose was to assess the role of protein expression and genetic polymorphisms of IL32 in colorectal cancer (CRC) susceptibility.
Materials and Methods: To gain insight into clinical significance of IL32 in Swedish patients with CRC, using enzyme-linked immunosorbent assay, we determined whether IL32 protein level is altered in CRC tissue (n=75) compared with paired normal tissue and in plasma from patients with CRC (n=94) compared with controls (n=81). The expression of IL32 protein was confirmed by immunohistochemistry (n=73). We used Luminex technology to investigate protein levels of the cytokines IL6, tumor necrosis factor-a (TNFa) and vascular endothelial growth factor (VEGF) to relate these to IL32 levels in CRC tissue. Three single nucleotide polymorphisms (SNPs) (rs28372698, rs12934561, rs4786370) of the IL32 gene have been proposed as modifiers for different diseases. The present study evaluated the susceptibility of patients possessing these SNPs to CRC. Using TaqMan SNP genotyping assays, these SNPs were screened in Swedish patients with CRC (n=465) and healthy controls (n=331).
Results: We found no significant differences in the genotypic frequencies between the patients and healthy controls and no relation to survival for any of the SNPs. However, the SNP rs12934561 was statisticalLY significant associated with older patients. IL32 protein was up-regulated in CRC tissue and related to IL6, TNFa, and VEGF, and seems to be modulated by SNP rs28372698. The IL32 protein level in CRC tissue also reflects both disseminated disease and location. Conclusion. Our results suggest that altered IL32 protein concentrations in CRC tissue and genotypic variants of IL32 are related to disseminated CRC.
Place, publisher, year, edition, pages
International Institute of Anticancer Research , 2018. Vol. 38, no 1, p. 321-328
Keywords [en]
Colorectal cancer, IL32, Protein expression, SNP, interleukin 32, interleukin 6, tumor necrosis factor, vasculotropin, IL32 protein, human, IL6 protein, human, interleukin derivative, tumor marker, vasculotropin A, VEGFA protein, human, adult, aged, Article, cancer growth, cancer staging, cancer susceptibility, comparative study, controlled study, disease free survival, DNA polymorphism, enzyme linked immunosorbent assay, female, follow up, genetic polymorphism, genetic variation, human, human tissue, immunohistochemistry, long term survival, major clinical study, male, priority journal, rectum cancer, single nucleotide polymorphism, survival analysis, upregulation, blood, colorectal tumor, early cancer diagnosis, genetic predisposition, genetics, metabolism, middle aged, pathology, procedures, Sweden, very elderly, Aged, 80 and over, Biomarkers, Tumor, Colorectal Neoplasms, Early Detection of Cancer, Enzyme-Linked Immunosorbent Assay, Genetic Predisposition to Disease, Humans, Interleukin-6, Interleukins, Polymorphism, Single Nucleotide, Tumor Necrosis Factor-alpha, Vascular Endothelial Growth Factor A
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:hj:diva-38510DOI: 10.21873/anticanres.12225ISI: 000419130100042PubMedID: 29277790Scopus ID: 2-s2.0-85039801563OAI: oai:DiVA.org:hj-38510DiVA, id: diva2:1173886
2018-01-152018-01-152019-12-20Bibliographically approved