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Evaluation of Fanconi anaemia genes FANCA, FANCC and FANCL in cervical cancer susceptibility
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. (Gyllensten)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Science for Life Laboratory, SciLifeLab. (Gyllensten)
2011 (English)In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 122, no 2, 377-381 p.Article in journal (Refereed) Published
Abstract [en]

Objective. Disrupting the function of any of the 13 Fanconi anaemia (FA) genes causes a DNA repair deficiency disorder, with patients being susceptible to a number of cancer types. Variation in the family of FA genes has been suggested to affect risk of cervical cancer. The current study evaluates the influence of three genes in the FA pathway on cervical cancer risk in Swedish women. Methods. TagSNPs in FANCA, FANCC and FANCL were selected using the Tagger algorithm in Haploview. A total of 81 tagSNPs were genotyped in 782 cases (CIN3 or ICC) and 775 controls using the Illumina GoldenGate Assay and statistically analyzed for association with cervical cancer. Results. 72 SNPs were successfully genotyped in >98% of the samples. Nominal associations were detected for FANCA rs11649196 (p = 0.05) and rs4128763 in FANCC (p = 0.02). The associations did not withstand correction for multiple testing. Conclusions. The current study does not support that genetic variation in FANCA, FANCC or FANCL genes affects susceptibility to cervical cancer in the Swedish population.

Place, publisher, year, edition, pages
2011. Vol. 122, no 2, 377-381 p.
Keyword [en]
Cervical cancer, FANCA, FANCC, FANCL, Fanconi anaemia, Genetic variants
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-158608DOI: 10.1016/j.ygyno.2011.04.014ISI: 000293681800034OAI: oai:DiVA.org:uu-158608DiVA: diva2:440130
Available from: 2011-09-12 Created: 2011-09-12 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Analysis of genetic susceptibility to cervical cancer using candidate gene and GWAS approaches
Open this publication in new window or tab >>Analysis of genetic susceptibility to cervical cancer using candidate gene and GWAS approaches
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cervical cancer is the forth most commonly diagnosed cancer among women worldwide. It is caused by persistent infection with an oncogenic type of Human Papillomavirus (HPV). The HPV is a necessary but not sufficient cause of cervical cancer. Environmental factors such as smoking, high parity and long-term use of oral contraceptives increases the risk of cervical cancer. Genetic factors also affect the risk of developing the disease. The aim of this thesis is to search for and evaluate genetic risk factors for cervical cancer using both a candidate gene approach and a genome-wide association study (GWAS).

Paper I examined the association of genetic variation in three Fanconi Anemia (FA) genes (FANCA, FANCC and FANCL), involved in DNA repair, with cervical cancer susceptibility in the Swedish population. No association was observed. Paper II evaluated the association of genetic variation in the TMC6 and TMC8 genes with susceptibility to cervical cancer in the Swedish population and an association of two SNPs (rs2290907 and rs16970849) with cervical cancer was observed.  In paper III the first GWAS performed in cervical cancer was reported. Three independent loci in the major histocompatibility complex (MHC) region at 6p21.3 were found to affect the susceptibility to cervical cancer. Paper IV examined the sequence variation in the TMC6 and TMC8 region and its association with cervical cancer. A highly polymorphic 21 bp sequence was identified and found to be repeated 5 to 42 times in both cases and controls. Lack of this repeat was associated with increased risk of cervical cancer. An intronic SNP (rs2926778) located in between the TNRC6C and TMC6 genes was also found to be associated with cervical cancer.

The thesis provides evidence for the importance of genes in the immune system for cervical cancer susceptibility. The genetic risk factors identified explain only a part of the genetic susceptibility, implying that other risk factors remains to be identified

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 50 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1100
Keyword
cervical cancer, association study, human papillomavirus, genetics, complex disease, TMC6, TMC8, MHC region
National Category
Medical Genetics
Research subject
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-248484 (URN)978-91-554-9234-2 (ISBN)
Public defence
2015-05-28, Auditorium Minus, Gustavianum, Akademigatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2015-05-06 Created: 2015-03-30 Last updated: 2015-07-07

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