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Gene polymorphisms, inflammatory diseases and cancer

Gene polymorphisms, inflammatory diseases and cancer
Gene polymorphisms, inflammatory diseases and cancer
Genes whose products play a critical role in regulation of the immune response include the human leucocyte antigen (HLA) and cytokine families of genes. The HLA genes are the most polymorphic found in the human genome, and the bulk of this polymorphism results in functional differences in expressed HLA molecules, resulting in inter-individual differences in presentation of peptide antigens to T-cells. In addition, a considerable number of cytokine-associated gene polymorphisms have been identified, the bulk of which occur in the upstream promoter sequences of these genes, which in many cases results in differential in vitro expression of the respective pro- or anti-inflammatory gene product. Particular HLA polymorphisms result in well-defined associations with a large number of immunologically-mediated diseases, including some diseases with known dietary risk factors. For example, individuals of HLA-DQA1*0501, DQB1*0201 genotype have a greater than 200-fold increased risk of developing intolerance to dietary wheat gluten (coeliac disease), and additional HLA-related factors may influence the development of malignant lymphoma within pre-existing coeliac disease. Similarly, HLA-DRB1 alleles sharing a common sequence motif constitute the primary known genetic risk factor for rheumatoid arthritis. The influence of polymorphisms associated with differential cytokine expression on disease susceptibility is currently of much interest. Most attention has been focused on associations with susceptibility to benign immunologically-mediated diseases, including a number of gut diseases. However, recent work from our laboratory indicates that cytokine polymorphisms may influence susceptibility to and prognosis in a number of different cancers, including malignant melanoma skin cancer and solid tumours which may be influenced by diet, such as prostate cancer (collaboration with the CRC/BPG UK Familial Prostate Cancer study). In addition, preliminary work suggests that dietary modulation of expression levels of certain cytokines in healthy human subjects may be genotype dependent.
gene polymorphisms, inflammatory diseases, cancer, human leucocyte antigen genes, cytokine genes
0029-6651
447-456
Calder, P. C.
532478ab-6402-49af-b4ba-97930b2a354b
Grimble, R. F.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Howell, W. M.
3100e4d2-8f29-4ca6-a95d-38a6a764865f
Calder, P. C.
532478ab-6402-49af-b4ba-97930b2a354b
Grimble, R. F.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Howell, W. M.
3100e4d2-8f29-4ca6-a95d-38a6a764865f

Calder, P. C., Grimble, R. F. and Howell, W. M. (2002) Gene polymorphisms, inflammatory diseases and cancer. Proceedings of the Nutrition Society, 61 (4), 447-456. (doi:10.1079/PNS2002186).

Record type: Article

Abstract

Genes whose products play a critical role in regulation of the immune response include the human leucocyte antigen (HLA) and cytokine families of genes. The HLA genes are the most polymorphic found in the human genome, and the bulk of this polymorphism results in functional differences in expressed HLA molecules, resulting in inter-individual differences in presentation of peptide antigens to T-cells. In addition, a considerable number of cytokine-associated gene polymorphisms have been identified, the bulk of which occur in the upstream promoter sequences of these genes, which in many cases results in differential in vitro expression of the respective pro- or anti-inflammatory gene product. Particular HLA polymorphisms result in well-defined associations with a large number of immunologically-mediated diseases, including some diseases with known dietary risk factors. For example, individuals of HLA-DQA1*0501, DQB1*0201 genotype have a greater than 200-fold increased risk of developing intolerance to dietary wheat gluten (coeliac disease), and additional HLA-related factors may influence the development of malignant lymphoma within pre-existing coeliac disease. Similarly, HLA-DRB1 alleles sharing a common sequence motif constitute the primary known genetic risk factor for rheumatoid arthritis. The influence of polymorphisms associated with differential cytokine expression on disease susceptibility is currently of much interest. Most attention has been focused on associations with susceptibility to benign immunologically-mediated diseases, including a number of gut diseases. However, recent work from our laboratory indicates that cytokine polymorphisms may influence susceptibility to and prognosis in a number of different cancers, including malignant melanoma skin cancer and solid tumours which may be influenced by diet, such as prostate cancer (collaboration with the CRC/BPG UK Familial Prostate Cancer study). In addition, preliminary work suggests that dietary modulation of expression levels of certain cytokines in healthy human subjects may be genotype dependent.

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More information

Published date: 2002
Keywords: gene polymorphisms, inflammatory diseases, cancer, human leucocyte antigen genes, cytokine genes

Identifiers

Local EPrints ID: 25644
URI: http://eprints.soton.ac.uk/id/eprint/25644
ISSN: 0029-6651
PURE UUID: 5171ee51-9fc1-464d-a7a1-f328e45d1051
ORCID for R. F. Grimble: ORCID iD orcid.org/0000-0002-6038-710X

Catalogue record

Date deposited: 11 Apr 2006
Last modified: 11 Mar 2021 02:35

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