Orozco, Gisela, Goh, Chee L., Al Olama, Ali Amin, Benlloch, Sara, Govindasami, Koveela, Guy, Michelle, Muir, Kenneth, Giles, Graham, Severi, Gianluca, Neal, David E., Hamdy, Freddie C., Donovan, Jenny, Kote-Jarai, Zsofia, Easton, Douglas F., Eyre, Steve and Eeles, Rosalind A. (2011) Common genetic variants associated with disease from genome-wide association studies are mutually exclusive in prostate cancer and rheumatoid arthritis. BJU International, Volume 111 (Number 7). pp. 1148-1155. doi:10.1111/j.1464-410X.2012.11492.x

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Abstract

Objectives: To investigate if potential common pathways exist for the pathogenesis of autoimmune disease and prostate cancer (PrCa). To ascertain if the single nucleotide polymorphisms (SNPs) reported by genome-wide association studies (GWAS) as being associated with susceptibility to PrCa are also associated with susceptibility to the autoimmune disease rheumatoid arthritis (RA).
Materials and Methods: The original Wellcome Trust Case Control Consortium (WTCCC) UK RA GWAS study was expanded to include a total of 3221 cases and 5272 controls.
In all, 37 germline autosomal SNPs at genome-wide significance associated with PrCa risk were identified from a UK/Australian PrCa GWAS. Allele frequencies were compared for these 37 SNPs between RA cases and controls using a chi-squared trend test and corrected for multiple testing (Bonferroni).
Results: In all, 33 SNPs were able to be analysed in the RA dataset. Proxies could not be located for the SNPs in 3q26, 5p15 and for two SNPs in 17q12. After applying a Bonferroni correction for the number of SNPs tested, the SNP mapping to CCHCR1 (rs130067) retained statistically significant evidence for association (P = 6 × 10–4; odds ratio [OR] = 1.15, 95% CI: 1.06–1.24); this has also been associated with psoriasis.
However, further analyses showed that the association of this allele was due to confounding by RA-associated HLA-DRB1 alleles.
Conclusions: There is currently no evidence that SNPs associated with PrCa at genome-wide significance are associated with the development of RA. Studies like this are important in determining if common genetic risk profiles might predispose individuals to many diseases, which could have implications for public health in terms of screening and chemoprevention.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions:	Faculty of Medicine > Warwick Medical School > Health Sciences Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Prostate -- Cancer, Rheumatoid arthritis, Genomes, Genomics
Journal or Publication Title:	BJU International
Publisher:	Wiley-Blackwell Publishing Ltd.
ISSN:	1464-1603
Official Date:	11 June 2011
Dates:	Date Event 11 June 2011 Published 18 September 2012 Available
Volume:	Volume 111
Number:	Number 7
Page Range:	pp. 1148-1155
DOI:	10.1111/j.1464-410X.2012.11492.x
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	Seventh Framework Programme (European Commission) (FP7), National Cancer Institute (NCI), Cancer Research UK (CRUK), Wellcome Trust (London, England), National Institute for Health Research (Great Britain) (NIHR), Institute of Cancer Research: Royal Cancer Hospital, Royal Marsden NHS Foundation Trust, Prostate Action
Grant number:	223175 (FP7); U19CA148537 (NCI); C5047/A10692 (CRUK); 095684/Z/11/A (WT)

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