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Human Molecular Genetics Advance Access published online on October 11, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl411
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© The Author 2006. Published by Oxford University Press. All rights reserved
Received June 20, 2006
Revised October 6, 2006
Accepted October 6, 2006

Article

Identification of Susceptibility Loci for Cervical Carcinoma by Genome Scan of Affected Sib-pairs

Malin T. Engelmark 1, Emma L. Ivansson 1, Jessica J. Magnusson 1, Inger M. Gustavsson 1, Anna H. Beskow 1, Patrik K.E. Magnusson 2, and Ulf B. Gyllensten 3 *

1 Department of Genetics and Pathology, Section of Medical Genetics, Rudbeck Laboratory, University of Uppsala, Uppsala, Sweden
2 Department of Genetics and Pathology, Section of Medical Genetics, Rudbeck Laboratory, University of Uppsala, Uppsala, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
3 Department of Genetics and Pathology, Section of Medical Genetics, Rudbeck Laboratory, University of Uppsala, S-751 85 Uppsala, Sweden

* To whom correspondence should be addressed.
Ulf B. Gyllensten, E-mail: ulf.gyllensten{at}genpat.uu.se


  Abstract

Cervical cancer is caused by a combination of environmental and genetic risk factors. Infection by oncogenic types of human papillomavirus (HPV) is recognised as the major environmental risk factor and epidemiological studies indicate that host genetic factors predispose to disease development. A number of genetic susceptibility factors have been proposed, but with exception of the human leukocyte antigen (HLA) class II loci, have not shown consistent results among studies. We have performed the first genomewide linkage scan using 278 affected sib-pairs (ASPs) to identify loci involved in susceptibility to cervical cancer. A two-step qualitative nonparametric linkage analysis using 387 microsatellites with an average spacing of 10.5 cM revealed excess allelic sharing at nine regions on eight chromosomes. These regions were further analysed with 125 markers to increase the map density to 1.28 cM. Nominal significant linkage was found for three of the nine loci (9q32 (MLS = 1.95, p < 0.002), 12q24 (MLS = 1.25, p < 0.015) and 16q24 (MLS = 1.35, p < 0.012)). These three regions have previously been connected to human cancers that share characteristics with cervical carcinoma, such as esophageal cancer and Hodgkin's lymphoma. A number of candidate genes involved in defence against viral infections, immune response and tumour suppression are found in these regions. One such gene is the thymic stromal co-transporter (TSCOT). Analyses of TSCOT single nucleotide polymorphisms (SNPs) further strengthen the linkage to this region (MLS = 2.40, p < 0.001). We propose that the 9q32 region contain susceptibility locus for cervical cancer and that TSCOT is a candidate gene potentially involved in genetic predisposition to this disease.


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