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Genetic variation i...
Genetic variation in RNASEL associated with prostate cancer risk and progression
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- Meyer, Mara S. (author)
- Department of Epidemiology, Harvard School of Public Health, Boston, USA
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- Penney, Kathryn L. (author)
- Department of Epidemiology, Harvard School of Public Health, Boston, USA
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- Stark, Jennifer R. (author)
- Department of Epidemiology, Harvard School of Public Health, Boston, USA
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- Schumacher, Fredrick R. (author)
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA
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- Sesso, Howard D. (author)
- Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, USA
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- Loda, Massimo (author)
- Harvard Radiation Oncology Program Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, USA
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- Fiorentino, Michelangelo (author)
- Harvard Radiation Oncology Program Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, USA
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- Finn, Stephen (author)
- Harvard Radiation Oncology Program Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, USA
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- Flavin, Richard J. (author)
- Harvard Radiation Oncology Program Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, USA
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- Kurth, Tobias (author)
- Department of Epidemiology, Harvard School of Public Health, Boston, USA; Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, USA
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- Price, Alkes L. (author)
- Department of Epidemiology, Harvard School of Public Health, Boston, USA; Department of Biostatistics, Harvard School of Public Health, Boston, USA
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- Giovannucci, Edward L. (author)
- Department of Epidemiology, Harvard School of Public Health, Boston, USA; Department of Nutrition, Harvard School of Public Health, Boston,USA
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- Fall, Katja, 1971- (author)
- Department of Epidemiology, Harvard School of Public Health, Boston, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
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- Stampfer, Meir J. (author)
- Department of Epidemiology, Harvard School of Public Health, Boston, USA; Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA
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- Ma, Jing (author)
- Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA
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- Mucci, Lorelei A. (author)
- Department of Epidemiology, Harvard School of Public Health, Boston, USA; Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA
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(creator_code:org_t)
- 2010-06-24
- 2010
- English.
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In: Carcinogenesis. - Oxford, United Kingdom : Oxford University Press. - 0143-3334 .- 1460-2180. ; 31:9, s. 1597-603
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https://urn.kb.se/re...
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Abstract
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- Variation in genes contributing to the host immune response may mediate the relationship between inflammation and prostate carcinogenesis. RNASEL at chromosome 1q25 encodes ribonuclease L, part of the interferon-mediated immune response to viral infection. We therefore investigated the association between variation in RNASEL and prostate cancer risk and progression in a study of 1286 cases and 1264 controls nested within the prospective Physicians' Health Study. Eleven single-nucleotide polymorphisms (SNPs) were selected using the web-based 'Tagger' in the HapMap CEPH panel (Utah residents of Northern and Western European Ancestry). Unconditional logistic regression models assessed the relationship between each SNP and incident advanced stage (T(3)/T(4), T(0)-T(4)/M(1) and lethal disease) and high Gleason grade (>/=7) prostate cancer. Further analyses were stratified by calendar year of diagnosis. Cox proportional hazards models examined the relationship between genotype and prostate cancer-specific survival. We also explored associations between genotype and serum inflammatory biomarkers interleukin-6 (IL-6), C-reactive protein (CRP) and tumor necrosis factor-alpha receptor 2 using linear regression. Individuals homozygous for the variant allele of rs12757998 had an increased risk of prostate cancer [AA versus GG; odds ratio (OR): 1.63, 95% confidence interval (CI): 1.18-2.25), and more specifically, high-grade tumors (OR: 1.90, 95% CI: 1.25-2.89). The same genotype was associated with increased CRP (P = 0.02) and IL-6 (P = 0.05) levels. Missense mutations R462Q and D541E were associated with an increased risk of advanced stage disease only in the pre-prostate-specific antigen era. There were no significant associations with survival. The results of this study support a link between RNASEL and prostate cancer and suggest that the association may be mediated through inflammation. These novel findings warrant replication in future studies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- art (subject category)
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- By the author/editor
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Meyer, Mara S.
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Penney, Kathryn ...
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Stark, Jennifer ...
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Schumacher, Fred ...
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Sesso, Howard D.
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Loda, Massimo
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Fiorentino, Mich ...
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Finn, Stephen
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Flavin, Richard ...
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Kurth, Tobias
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Price, Alkes L.
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Giovannucci, Edw ...
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Fall, Katja, 197 ...
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Stampfer, Meir J ...
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Ma, Jing
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Mucci, Lorelei A ...
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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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Carcinogenesis
- By the university
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Örebro University
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Karolinska Institutet