Abstract
With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele −8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 × 10−11). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of ∼8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry.
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Acknowledgements
We thank the men with cancer and their family members whose contribution made this work possible. We also thank the nurses at Noatun and personnel at the deCODE core facilities for their hard work and enthusiasm. In addition, we thank the following individuals at the Department of Pathology at Landspitali University-Hospital for their contributions: A. Arason, G. Johannesdottir, K. Olafsdottir and S. Kristjansdottir. We also thank the staff at the Icelandic Cancer Registry for providing patient lists. We thank Regional Cancer Registries in Umeå, Uppsala, Stockholm-Gotland and Lindköping and all urologists who recruited their patients to this study and provided clinical data to the national registry of prostate cancer. We also thank P. Stattin, J. Adolfsson and E. Varenhorst as regional coordinators in CAPS and the personnel at the Medical Biobank in Umeå. The CAPS study has been supported by grants from the Swedish Cancer Foundation and partially funded by a US National Cancer Institute grant (CA 1R01CA105055-01A1). We also thank participants and clinicians at Northwestern University, the University of Chicago and the University of Michigan for their contribution to the collection of samples and clinical data used in this study.
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L.T.A., P.S., J.G., A.H., A.S., A.B., J.B.C., J.S., M.J., J.K., D.N.M., S.G., K.A., B.B., L.L.R., A.O., T.B., M.A., O.S.A., J.T.B., D.G., A.G., G.T., A.M., K.K., J.R.G., A.K., U.T. and K.S. own stock or stock options in deCODE genetics.
Supplementary information
Supplementary Fig. 1
A phylogenetic network of 46 SNPs and the DG8S737 microsatellite for the HapMap samples. (PDF 127 kb)
Supplementary Fig. 2
Linkage disequilibrium between the 17 SNPs and the –8 allele of DG8S737 typed in the CEU and the African American populations. (PDF 219 kb)
Supplementary Table 1
Markers and primers. (PDF 90 kb)
Supplementary Table 2
SNP markers genotyped in the 600-kb region on chromosome 8q24. (PDF 51 kb)
Supplementary Table 3
LD between the –8 allele of DG8S737 and allele A of rs1447295, and the 19 SNPs belonging to the equivalent class of rs1447295 in HapMap Caucasians (CEU). (PDF 65 kb)
Supplementary Table 4
Frequencies of haplotype groups (DG8S737 and rs1447295) in three Caucasian populations from Iceland, Sweden and the US. (PDF 54 kb)
Supplementary Table 5
The frequency of the various alleles of the microsatellite marker DS8S737 in the four populations studied. (PDF 26 kb)
Supplementary Table 6
Count of individuals and yields for DG8S737 and rs1447295 in the four study groups from Iceland, Sweden and the US. (PDF 59 kb)
Supplementary Table 7
Comparison of the relative risk of allele –8 of DG8S737 and allele A of rs1447295 under the multiplicative model with that of model-free estimates of the genotype relative risks of heterozygous carriers (0X), homozygous carriers (XX) and non-carriers (00). (PDF 82 kb)
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Amundadottir, L., Sulem, P., Gudmundsson, J. et al. A common variant associated with prostate cancer in European and African populations. Nat Genet 38, 652–658 (2006). https://doi.org/10.1038/ng1808
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DOI: https://doi.org/10.1038/ng1808
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