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| Genome-wide association study of prostate cancer identifies a second risk locus at 8q24 |
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| Author(s): Yeager M (Yeager, Meredith), Orr N (Orr, Nick), Hayes RB (Hayes, Richard B.), Jacobs KB (Jacobs, Kevin B.), Kraft P (Kraft, Peter), Wacholder S (Wacholder, Sholom), Minichiello MJ (Minichiello, Mark J.), Fearnhead P (Fearnhead, Paul), Yu K (Yu, Kai), Chatterjee N (Chatterjee, Nilanjan), Wang ZM (Wang, Zhaoming), Welch R (Welch, Robert), Staats BJ (Staats, Brian J.), Calle EE (Calle, Eugenia E.), Feigelson HS (Feigelson, Heather Spencer), Thun MJ (Thun, Michael J.), Rodriguez C (Rodriguez, Carmen), Albanes D (Albanes, Demetrius), Virtamo J (Virtamo, Jarmo), Weinstein S (Weinstein, Stephanie), Schumacher FR (Schumacher, Fredrick R.), Giovannucci E (Giovannucci, Edward), Willett WC (Willett, Walter C.), Cancel-Tassin G (Cancel-Tassin, Geraldine), Cussenot O (Cussenot, Olivier), Valeri A (Valeri, Antoine), Andriole GL (Andriole, Gerald L.), Gelmann EP (Gelmann, Edward P.), Tucker M (Tucker, Margaret), Gerhard DS (Gerhard, Daniela S.), Fraumeni JF (Fraumeni, Joseph F., Jr.), Hoover R (Hoover, Robert), Hunter DJ (Hunter, David J.), Chanock SJ (Chanock, Stephen J.), Thomas G (Thomas, Gilles) |
| Source: NATURE GENETICS Volume: 39 Issue: 5 Pages: 645-649 Published: MAY 2007 |
| Times Cited: 262 References: 26 |
| Abstract: Recently, common variants on human chromosome 8q24 were found to be associated with prostate cancer risk. While conducting a genome-wide association study in the Cancer Genetic Markers of Susceptibility project with 550,000 SNPs in a nested case-control study ( 1,172 cases and 1,157 controls of European origin), we identified a new association at 8q24 with an independent effect on prostate cancer susceptibility. The most significant signal is 70 kb centromeric to the previously reported SNP, rs1447295, but shows little evidence of linkage disequilibrium with it. A combined analysis with four additional studies ( total: 4,296 cases and 4,299 controls) confirms association with prostate cancer for rs6983267 in the centromeric locus ( P = 9.42 x 10(-13;) heterozygote odds ratio (OR): 1.26, 95% confidence interval ( c. i.): 1.13 - 1.41; homozygote OR: 1.58, 95% c. i.: 1.40 - 1.78). Each SNP remained significant in a joint analysis after adjusting for the other ( rs1447295 P = 1.41 x 10(-11); rs6983267 P = 6.62 x 10(-10)). These observations, combined with compelling evidence for a recombination hotspot between the two markers, indicate the presence of at least two independent loci within 8q24 that contribute to prostate cancer in men of European ancestry. We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 ( 21% versus 9%). |
| Document Type: Article |
| Language: English |
| Reprint Address: Chanock, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA |
Addresses:
1. NCI, Div Canc Epidemiol & Genet, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA
2. NCI, Pediat Oncol Branch, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA
3. NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA
4. Bioinformed Consulting Serv, Gaithersburg, MD 20877 USA
5. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA
6. Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England
7. Univ Lancaster, Dept Math & Stat, Lancaster LA1 4YF, England
8. Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA
9. Natl Inst Publ Hlth, Dept Hlth Promot & Chron Dis Prevent, FIN-00300 Helsinki, Finland
10. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA
11. Hop Tenon, AP HP, CeRePP, F-75970 Paris, France
12. Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63108 USA
13. Columbia Univ, Div Hematol & Oncol, New York, NY 10032 USA
14. NCI, Off Canc Genom, NIH, DHHS, Bethesda, MD 20892 USA |
| Publisher: NATURE PUBLISHING GROUP, 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA |
| Subject Category: Genetics & Heredity |
| IDS Number: 160VU |
| ISSN: 1061-4036 |
| DOI: 10.1038/ng2022 |
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