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Common genetic variants associated with disease from genome‐wide association studies are mutually exclusive in prostate cancer and rheumatoid arthritis

Arthritis Research UK Epidemiology Unit, School of Translational Medicine, University of Manchester, Manchester Oncogenetics Team, The Institute of Cancer Research, Sutton, Surrey Cancer Research UK Centre for Cancer Genetic Epidemiology, Strangeways Laboratory, University of Cambridge, Cambridge Health Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, UK Cancer Epidemiology Centre, The Cancer Council Victoria, Carlton, Vic Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Melbourne, Vic, Australia Surgical Oncology (Uro-Oncology: S4), University of Cambridge, Addenbrooke's Hospital, Cambridge Cancer Research UK Cambridge Research Institute, Cambridge Nuffield Department of Surgery, University of Oxford, Oxford Faculty of Medical Science, University of Oxford, John Radcliffe Hospital, Oxford School of Social and Community Medicine, University of Bristol, BristolDepartments of Public Health Primary Care Oncology, University of Cambridge, Cambridge Academic Urology Unit, Royal Marsden Foundation NHS Trust, Sutton, Surrey, UK.
BJU International (Impact Factor: 3.53). 09/2012; 111(7). DOI: 10.1111/j.1464-410X.2012.11492.x
Source: PubMed

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.

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    • "Several susceptibility loci reside in the HLA region on chromosome 6 and within this region, normal genetic variation may increase a patient's susceptibility to or severity of rheumatoid disease. Although many genetic variants have been identified [1] [2] [3] [4], the impact of individual variants on the risk of developing RA is low. Research into the functional mechanisms by which these genetic variants confer disease susceptibility is on-going, with the ultimate goal of identifying discrete biological pathways which pathologically induce chronic inflammation. "

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