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Variants of chemokine receptor 2 and interleukin 4 receptor, but not interleukin 10 or Fas ligand, increase risk of cervical cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Genomics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2007 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 121, no 11, 2451-2457 p.Article in journal (Refereed) Published
Abstract [en]

Cervical cancer is caused by persistent infection of oncogenichuman papillomavirus (HPV). Most infected women clear the viruswithout developing cervical lesions and it is likely that immunologicalhost factors affect susceptibility to cervical cancer. Theimpact of the human leukocyte antigen (HLA) locus on the risk ofcervical cancer is established and several other genes involved inimmunological pathways have been suggested as biologically plausiblecandidates. The aim of this study was to examine the potentialrole of polymorphisms in 4 candidate genes by analysis of1,306 familial cervical cancer cases and 288 controls. The followinggenes and polymorphisms were studied: Chemokine receptor2 (CCR-2) V64I; Interleukin 4 receptor a (IL-4R) I75V, S503P andQ576R; Interleukin 10 (IL-10) 2592; and Fas ligand (FasL) 2844.The CCR-2 64I variant was associated with decreased risk of cervicalcancer; homozygote carriers of the 64I variant had an oddsratio of 0.31 (0.12–0.77). This association was detected in both carriersand noncarriers of the HLA DQB1*0602 cervical cancer riskallele. The IL-4R 75V variant was associated with increased riskof cervical tumors, cases homozygote for 75V had an odds ratio of1.91 (1.27–2.86) with a tendency that the association was strongerin noncarriers of the DQB1*0602 allele. We did not find any associationfor IL-10 2592, or FasL 2844, previously reported to beassociated with cervical cancer in the Dutch and Chinese populations,respectively.

Place, publisher, year, edition, pages
2007. Vol. 121, no 11, 2451-2457 p.
Keyword [en]
CCR-2, IL-4R, IL-10, FasL, polymorphisms, cervical cancer, host factors
National Category
Medical and Health Sciences
Research subject
Genetics
Identifiers
URN: urn:nbn:se:uu:diva-98056DOI: 10.1002/ijc.22989ISI: 000250559600013PubMedID: 17688234OAI: oai:DiVA.org:uu-98056DiVA: diva2:173224
Available from: 2009-02-20 Created: 2009-02-04 Last updated: 2013-03-14Bibliographically approved
In thesis
1. Contribution of Immunogenetic Factors in Susceptibility to Cervical Cancer
Open this publication in new window or tab >>Contribution of Immunogenetic Factors in Susceptibility to Cervical Cancer
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cervical cancer is the second most common cancer in women worldwide. Persistent infection by an oncogenic type of human papillomavirus (HPV) is a necessary but not sufficient cause and there is also a genetic component. This thesis aims to identify host genetic risk factors for cervical cancer based on the hypothesis that susceptibility is affected by genetic variation in the immune response towards HPV infection.

Paper I analyzed allergy in sons and cervical cancer in their mothers, and revealed an inverse association between cervical cancer and allergy across generations. Mothers of allergic sons have a lower incidence of cervical cancer, supporting the importance of immunogenetic factors. Paper II investigated the HPV type in 1079 women diagnosed 1965-1993. All women were from families with at least two affected. It appeared that HPV 16 was becoming less common with time. There was no evidence that related women were prone to infection by the same type, indicating that the immunogenetic factors act in a general, rather than an HPV type specific, manner. Paper III and IV analysed the association of candidate genes with susceptibility to cervical cancer in 1306 women with cervical cancer in situ and 288 unrelated controls. Paper III showed the association of variation in the two immune response genes chemokine receptor 2 (CCR-2) and interleukin 4 receptor (IL-4R) with cervical cancer. In paper IV variation at several loci in the MHC region was studied and the importance of the HLA class II locus DQB1 emphasized.

This thesis work supports the contribution of genes of the immune system to cervical cancer susceptibility. The genetic risk factors so far identified account for only a part of the genetic susceptibility, which implies that other yet undiscovered variants of importance remain to be identified.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 55 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 419
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-9552 (URN)978-91-554-7410-2 (ISBN)
Public defence
2009-03-13, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, Uppsala, 09:15 (English)
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Supervisors
Available from: 2009-02-20 Created: 2009-02-04 Last updated: 2009-02-20Bibliographically approved

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Gustavsson, Inger M.Magnusson, JessicaGyllensten, Ulf B

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