Protein expression and genetic variation of IL32 and association with colorectal cancer in Swedish patients

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)

Nyckelord

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)