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No evidence of the involvement of the Fas -670 promoter polymorphism in cervical cancer in situ
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
2004 In: International Journal of Cancer, ISSN 00207136, Vol. 112, no 6, 1084-5 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2004. Vol. 112, no 6, 1084-5 p.
Identifiers
URN: urn:nbn:se:uu:diva-94382OAI: oai:DiVA.org:uu-94382DiVA: diva2:168213
Available from: 2006-04-28 Created: 2006-04-28Bibliographically approved
In thesis
1. Identifying Risk Genes for Cervical Cancer: Using Affected Sib-Pairs and Case-Control Materials from Sweden
Open this publication in new window or tab >>Identifying Risk Genes for Cervical Cancer: Using Affected Sib-Pairs and Case-Control Materials from Sweden
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cervical cancer is a multifactorial disease. Infection by oncogenic types of the human papillomavirus (HPV) is the major environmental risk factor and host genetic susceptibility also influences disease development.

The aim of this thesis is to identify and analyse risk genes involved in the genetic predisposition to cervical carcinoma. A unique and extensive population-based affected sib-pair (ASP) material and a large case-control sample were used in the investigations.

In paper I the human leukocyte antigen (HLA) class II DQB1 and DRB1 loci are confirmed, for the first time in a family-based material, as genetic susceptibility factors for cervical cancer. It is also proposed that the HLA class II DPB1 locus independently contributes to risk of developing disease. In addition, no evidence is found for an involvement of the class I HLA-B and HLA-A loci in the genetic predisposition. Paper II conclude that the Fas receptor –670 single nucleotide polymorphism (SNP) do not have a major impact on the susceptibility to cervical carcinoma in situ in the Swedish population. In paper III we show that interactions between the HPV16 E6 gene subtype and host HLA class II genotype potentially occur during infection and disease progression. Paper IV suggests that three chromosomal regions, 9q32, 12q24 and 16q24, contain risk factors of low to moderate effects on cervical cancer development. In paper V linkage signals are further identified between a 9q32 gene encoding the thymic stromal co-transporter (TSCOT) and the disease in ASPs with mean age over 30.5 years at diagnosis within the sib-pair.

These findings are important contributions towards understanding more about the aetiology of this complex cancer. The identification of new susceptibility regions opens up for further characterisation, replication and candidate gene analysis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 102 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 146
Keyword
Medicine, Cervical cancer, HPV, Affected sib-pairs, HLA, Fas, Genomewide scan, 9q32, TSCOT, Medicin
Identifiers
urn:nbn:se:uu:diva-6826 (URN)91-554-6545-5 (ISBN)
Public defence
2006-05-19, Rudbecksalen, C11, Rudbecklaboratoriet, Uppsala, 09:15
Opponent
Supervisors
Available from: 2006-04-28 Created: 2006-04-28Bibliographically approved

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