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Genetic variation in RNASEL associated with prostate cancer risk and progression

Meyer, Mara S. (author)
Department of Epidemiology, Harvard School of Public Health, Boston, USA
Penney, Kathryn L. (author)
Department of Epidemiology, Harvard School of Public Health, Boston, USA
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
Sesso, Howard D. (author)
Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, USA
Loda, Massimo (author)
Harvard Radiation Oncology Program Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, USA
Fiorentino, Michelangelo (author)
Harvard Radiation Oncology Program Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, USA
Finn, Stephen (author)
Harvard Radiation Oncology Program Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, USA
Flavin, Richard J. (author)
Harvard Radiation Oncology Program Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, USA
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
Price, Alkes L. (author)
Department of Epidemiology, Harvard School of Public Health, Boston, USA; Department of Biostatistics, Harvard School of Public Health, Boston, USA
Giovannucci, Edward L. (author)
Department of Epidemiology, Harvard School of Public Health, Boston, USA; Department of Nutrition, Harvard School of Public Health, Boston,USA
Fall, Katja, 1971- (author)
Department of Epidemiology, Harvard School of Public Health, Boston, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
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
Ma, Jing (author)
Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA
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.
In: Carcinogenesis. - Oxford, United Kingdom : Oxford University Press. - 0143-3334 .- 1460-2180. ; 31:9, s. 1597-603
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  • Journal article (peer-reviewed)
Abstract Subject headings
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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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