Genetic variation in RNASEL associated with prostate cancer risk and progression
| Autor: | Mara S. Meyer, Fredrick R. Schumacher, Michelangelo Fiorentino, Jing Ma, Stephen P. Finn, Kathryn L. Penney, Richard Flavin, Lorelei A. Mucci, Edward Giovannucci, Alkes L. Price, Massimo Loda, Howard D. Sesso, Meir J. Stampfer, Jennifer R. Stark, Tobias Kurth, Katja Fall |
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| Přispěvatelé: | Meyer MS, Penney KL, Stark JR, Schumacher FR, Sesso HD, Loda M, Fiorentino M, Finn S, Flavin RJ, Kurth T, Price AL, Giovannucci EL, Fall K, Stampfer MJ, Ma J, Mucci LA |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Cancer Research Tumor suppressor gene Genotype Mutation Missense Single-nucleotide polymorphism Biology urologic and male genital diseases Polymorphism Single Nucleotide Prostate cancer Genetic variation Endoribonucleases medicine Humans Prospective Studies Aged Neoplasm Staging Genetics Aged 80 and over Molecular Epidemiology Interleukin-6 RNASEL Gene Cancer Prostatic Neoplasms General Medicine Middle Aged medicine.disease prostate cancer RNASEL C-Reactive Protein Tumor progression Case-Control Studies biology.protein Disease Progression Ribonuclease L |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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