Genome-wide association study and functional follow-up identify 14q12 as a candidate risk locus for cervical cancer.
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Authors
Dennis, Joe
Fachal, Laura
Schürmann, Peter
Bousset, Kristine
Hülse, Fabienne
Mao, Qianqian
Wang, Yingying
Jentschke, Matthias
Böhmer, Gerd
Strauß, Hans-Georg
Hirchenhain, Christine
Schmidmayr, Monika
Müller, Florian
Runnebaum, Ingo
Hein, Alexander
Stübs, Frederik
Koch, Martin
Ruebner, Matthias
Beckmann, Matthias W
Fasching, Peter A
Luyten, Alexander
Dürst, Matthias
Hillemanns, Peter
Easton, Douglas F
Publication Date
2022-08-17Journal Title
Hum Mol Genet
ISSN
0964-6906
Publisher
Oxford University Press (OUP)
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Ramachandran, D., Dennis, J., Fachal, L., Schürmann, P., Bousset, K., Hülse, F., Mao, Q., et al. (2022). Genome-wide association study and functional follow-up identify 14q12 as a candidate risk locus for cervical cancer.. Hum Mol Genet https://doi.org/10.1093/hmg/ddac031
Abstract
Cervical cancer is among the leading causes of cancer-related death in females worldwide. Infection by human papillomavirus (HPV) is an established risk factor for cancer development. However, genetic factors contributing to disease risk remain largely unknown. We report on a genome-wide association study (GWAS) on 375 German cervical cancer patients and 866 healthy controls, followed by a replication study comprising 658 patients with invasive cervical cancer, 1361 with cervical dysplasia and 841 healthy controls. Functional validation was performed for the top GWAS variant on chromosome 14q12 (rs225902, close to PRKD1). After bioinformatic annotation and in silico predictions, we performed transcript analysis in a cervical tissue series of 317 samples and demonstrate rs225902 as an expression quantitative trait locus (eQTL) for FOXG1 and two tightly co-regulated long non-coding RNAs at this genomic region, CTD-2251F13 (lnc-PRKD1-1) and CTD-2503I6 (lnc-FOXG1-6). We also show allele-specific effects of the 14q12 variants via luciferase assays. We propose a combined effect of genotype, HPV status and gene expression at this locus on cervical cancer progression. Taken together, this work uncovers a potential candidate locus with regulatory functions and contributes to the understanding of genetic susceptibility to cervical cancer.
Embargo Lift Date
2023-02-14
Identifiers
External DOI: https://doi.org/10.1093/hmg/ddac031
This record's URL: https://www.repository.cam.ac.uk/handle/1810/332977
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