Gene and pathway level analyses of germline DNA-repair gene variants and prostate cancer susceptibility using the iCOGS-genotyping arrayReportar como inadecuado


Gene and pathway level analyses of germline DNA-repair gene variants and prostate cancer susceptibility using the iCOGS-genotyping array


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Publication Date: 2016-03-10

Journal Title: British Journal of Cancer

Publisher: Nature Publishing Group

Volume: 114

Pages: 945-952

Language: English

Type: Article

Metadata: Show full item record

Citation: Saunders, E. J., Dadaev, T., Leongamornlert, D. A., Al Olama, A. A., Benlloch, S., Giles, G. G., Wiklund, F., et al. (2016). Gene and pathway level analyses of germline DNA-repair gene variants and prostate cancer susceptibility using the iCOGS-genotyping array. British Journal of Cancer, 114 945-952.

Description: This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/bjc.2016.50

Abstract: Background: Germline mutations within DNA-repair genes are implicated in susceptibility to multiple forms of cancer. For prostate cancer (PrCa), rare mutations in BRCA2 and BRCA1 give rise to moderately elevated risk, whereas two of ~100 common, low-penetrance PrCa susceptibility variants identified so far by genome-wide association studies implicate RAD51B and RAD23B. Methods: Genotype data from the iCOGS array were imputed to the 1000 genomes phase 3 reference panel for 21 780 PrCa cases and 21 727 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. We subsequently performed single variant, gene and pathway-level analyses using 81 303 SNPs within 20 Kb of a panel of 179 DNA-repair genes. Results: Single SNP analyses identified only the previously reported association with RAD51B. Gene-level analyses using the SKAT-C test from the SNP-set (Sequence) Kernel Association Test (SKAT) identified a significant association with PrCa for MSH5. Pathway-level analyses suggested a possible role for the translesion synthesis pathway in PrCa risk and Homologous recombination/Fanconi Anaemia pathway for PrCa aggressiveness, even though after adjustment for multiple testing these did not remain significant. Conclusions: MSH5 is a novel candidate gene warranting additional follow-up as a prospective PrCa-risk locus. MSH5 has previously been reported as a pleiotropic susceptibility locus for lung, colorectal and serous ovarian cancers.

Keywords: DNA repair, prostate cancer, genome-wide association study, GWAS, iCOGS

Embargo Lift Date: 2300-01-01

Identifiers:

This record's URL: http://dx.doi.org/10.1038/bjc.2016.50https://www.repository.cam.ac.uk/handle/1810/255991

Rights: Attribution 2.0 UK: England & Wales

Licence URL: http://creativecommons.org/licenses/by/2.0/uk/





Autor: Saunders, Edward J.Dadaev, TokhirLeongamornlert, Daniel A.Al Olama, Ali AminBenlloch, SaraGiles, Graham G.Wiklund, FredrikGrönber

Fuente: https://www.repository.cam.ac.uk/handle/1810/255991



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