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Germline variants i...
Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality : an analysis of 12,082 prostate cancer cases
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- FitzGerald, L. M. (author)
- Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic 3004, Australia;Univ Tasmania, Menzies Inst Med Res, Canc Genet & Immunol, Hobart, Tas 7001, Australia
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- Zhao, S. (author)
- NIEHS, Biostat & Computat Biol Branch, Res Triangle Pk, NC 27709 USA
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- Leonardson, A. (author)
- Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA
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- Geybels, M. S. (author)
- Maastricht Univ, Med Ctr, GROW Sch Oncol & Dev Biol, Dept Epidemiol, NL-6211 LK Maastricht, Netherlands;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA
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- Kolb, S. (author)
- Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA
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- Lin, D. W. (author)
- Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA
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- Wright, J. L. (author)
- Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA
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- Eeles, R. (author)
- Royal Marsden Natl Hlth Serv Fdn Trust, London, England;Royal Marsden Natl Hlth Serv Fdn Trust, Sutton SW3 6JJ, Surrey, England;Inst Canc Res, Sutton SM2 5NG, Surrey, England
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- Kote-Jarai, Z. (author)
- Inst Canc Res, Sutton SM2 5NG, Surrey, England
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- Govindasami, K. (author)
- Inst Canc Res, Sutton SM2 5NG, Surrey, England
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- Giles, G. G. (author)
- Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Carlton, Vic 3053, Australia;Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic 3004, Australia
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- Southey, M. C. (author)
- Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3010, Australia
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- Schleutker, J. (author)
- Turku Univ Hosp, Dept Med Genet, Tuch Microbiol & Genet, Turku 20520, Finland;Univ Turku, Dept Med Biochem & Genet, Inst Biomed, Turku 20014, Finland
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- Tammela, T. L. (author)
- Tampere Univ Hosp, Dept Urol, Tampere 33521, Finland;Univ Tampere, Prostate Canc Res Ctr, Sch Med, Tampere 33100, Finland
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- Sipeky, C. (author)
- Univ Turku, Dept Med Biochem & Genet, Inst Biomed, Turku 20014, Finland
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- Penney, K. L. (author)
- Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA;Brigham & Womens Hosp, Dept Med, Charming Div Network Med, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA
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- Stampfer, M. J. (author)
- Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA;Brigham & Womens Hosp, Dept Med, Charming Div Network Med, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA
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- Gronberg, H. (author)
- Karolinska Institutet
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- Wiklund, F. (author)
- Karolinska Institutet
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- Stattin, P. (author)
- Uppsala universitet,Umeå universitet,Urologi och andrologi,Urologkirurgi,Umea Univ, Dept Surg & Perioperat Sci, S-90187 Umea, Sweden
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- Hugosson, J. (author)
- Univ Goteborgs, Inst Clin Sci, Dept Urol, S-40530 Goteborgs, Sweden
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- Karyadi, D. M. (author)
- NHGRI, NIH, Bethesda, MD 20854 USA
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- Ostrander, E. A. (author)
- NHGRI, NIH, Bethesda, MD 20854 USA
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- Feng, Z. (author)
- MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA
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- Stanford, J. L. (author)
- Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA
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(creator_code:org_t)
- 2018-01-03
- 2018
- English.
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In: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 21:2, s. 228-237
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Abstract
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- Background Prostate cancer (PCa) is a leading cause of mortality and genetic factors can influence tumour aggressiveness. Several germline variants have been associated with PCa-specific mortality (PCSM), but further replication evidence is needed. Methods Twenty-two previously identified PCSM-associated genetic variants were genotyped in seven PCa cohorts (12,082 patients; 1544 PCa deaths). For each cohort, Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for risk of PCSM associated with each variant. Data were then combined using a meta-analysis approach. Results Fifteen SNPs were associated with PCSM in at least one of the seven cohorts. In the meta-analysis, after adjustment for clinicopathological factors, variants in the MGMT (rs2308327; HR 0.90; p-value = 3.5 x 10(-2)) and IL4 (rs2070874; HR 1.22; p-value = 1.1 x 10(-3)) genes were confirmed to be associated with risk of PCSM. In analyses limited to men diagnosed with local or regional stage disease, a variant in AKT1, rs2494750, was also confirmed to be associated with PCSM risk (HR 0.81; p-value = 3.6 x 10(-2)). Conclusions This meta-analysis confirms the association of three genetic variants with risk of PCSM, providing further evidence that genetic background plays a role in PCa-specific survival. While these variants alone are not sufficient as prognostic biomarkers, these results may provide insights into the biological pathways modulating tumour aggressiveness.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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FitzGerald, L. M ...
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Zhao, S.
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Leonardson, A.
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Geybels, M. S.
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Kolb, S.
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Lin, D. W.
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show more...
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Wright, J. L.
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Eeles, R.
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Kote-Jarai, Z.
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Govindasami, K.
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Giles, G. G.
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Southey, M. C.
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Schleutker, J.
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Tammela, T. L.
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Sipeky, C.
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Penney, K. L.
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Stampfer, M. J.
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Gronberg, H.
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Wiklund, F.
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Stattin, P.
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Hugosson, J.
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Karyadi, D. M.
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Ostrander, E. A.
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Feng, Z.
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Stanford, J. L.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Prostate Cancer ...
- By the university
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Umeå University
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Uppsala University
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Karolinska Institutet