BACKGROUND: Inflammation has been hypothesized to play an important etiological role in the initiation or progression of prostate cancer. Circulating levels of the systemic inflammation marker C-reactive protein (CRP) have been associated with increased risk of prostate cancer. We investigated the role of genetic variation in CRP and prostate cancer, under the hypothesis that variants may alter risk of disease. METHODS: We undertook a case-control study nested within the prospective Physicians' Health Study among 1,286 men with incident prostate cancer and 1,264 controls. Four single-nucleotide polymorphisms (SNPs) were selected to capture the common genetic variation across CRP (r(2) > 0.8). We used unconditional logistic regression to assess the association between each SNP and risk of prostate cancer. Linear regression models explored associations between each genotype and plasma CRP levels. RESULTS: None of the CRP SNPs were associated with prostate cancer overall. Individuals with one copy of the minor allele (C) in rs1800947 had an increased risk of high-grade prostate cancer (OR: 1.7; 95% CI: 1.1-2.8), and significantly lower mean CRP levels (P-value <0.001), however, we found no significant association with lethal disease. Mean CRP levels were significantly elevated in men with one or two copies of the minor allele in rs3093075 and rs1417939, but these were unrelated to prostate cancer risk. CONCLUSION: Our findings suggest that SNPs in the CRP gene are not associated with risk of overall or lethal prostate cancer. Polymorphisms in CRP rs1800947 may be associated with higher grade disease, but our results require replication in other cohorts.
BACKGROUND:Inflammation has been hypothesized to play an important etiological role in the initiation or progression of prostate cancer. Circulating levels of the systemic inflammation marker C-reactive protein (CRP) have been associated with increased risk of prostate cancer. We investigated the role of genetic variation in CRP and prostate cancer, under the hypothesis that variants may alter risk of disease. METHODS: We undertook a case-control study nested within the prospective Physicians' Health Study among 1,286 men with incident prostate cancer and 1,264 controls. Four single-nucleotide polymorphisms (SNPs) were selected to capture the common genetic variation across CRP (r(2) > 0.8). We used unconditional logistic regression to assess the association between each SNP and risk of prostate cancer. Linear regression models explored associations between each genotype and plasma CRP levels. RESULTS: None of the CRP SNPs were associated with prostate cancer overall. Individuals with one copy of the minor allele (C) in rs1800947 had an increased risk of high-grade prostate cancer (OR: 1.7; 95% CI: 1.1-2.8), and significantly lower mean CRP levels (P-value <0.001), however, we found no significant association with lethal disease. Mean CRP levels were significantly elevated in men with one or two copies of the minor allele in rs3093075 and rs1417939, but these were unrelated to prostate cancer risk. CONCLUSION: Our findings suggest that SNPs in the CRP gene are not associated with risk of overall or lethal prostate cancer. Polymorphisms in CRPrs1800947 may be associated with higher grade disease, but our results require replication in other cohorts.
Authors: Claire Siemes; Loes E Visser; Jan-Willem W Coebergh; Ted A W Splinter; Jacqueline C M Witteman; André G Uitterlinden; Albert Hofman; Huibert A P Pols; Bruno H Ch Stricker Journal: J Clin Oncol Date: 2006-11-20 Impact factor: 44.544
Authors: Peter A McArdle; Khurram Mir; A S K Almushatat; A Michael Wallace; Mark A Underwood; Donald C McMillan Journal: Urol Int Date: 2006 Impact factor: 2.089
Authors: Dana C Crawford; Christopher L Sanders; Xiaoting Qin; Joshua D Smith; Cynthia Shephard; Michelle Wong; Laura Witrak; Mark J Rieder; Deborah A Nickerson Journal: Circulation Date: 2006-11-13 Impact factor: 29.690
Authors: Elizabeth A Platz; Siobhan Sutcliffe; Angelo M De Marzo; Charles G Drake; Nader Rifai; Ann W Hsing; Ashraful Hoque; Marian L Neuhouser; Phyllis J Goodman; Alan R Kristal Journal: Cancer Causes Control Date: 2010-02-05 Impact factor: 2.506
Authors: Ming-Hsi Wang; Kathy J Helzlsouer; Michael W Smith; Judith A Hoffman-Bolton; Sandra L Clipp; Viktoriya Grinberg; Angelo M De Marzo; William B Isaacs; Charles G Drake; Yin Yao Shugart; Elizabeth A Platz Journal: Prostate Date: 2009-06-01 Impact factor: 4.104
Authors: Elizabeth A Platz; Angelo M De Marzo; Thomas P Erlinger; Nader Rifai; Kala Visvanathan; Sandra C Hoffman; Kathy J Helzlsouer Journal: Prostate Date: 2004-06-01 Impact factor: 4.104
Authors: C H Hennekens; J E Buring; J E Manson; M Stampfer; B Rosner; N R Cook; C Belanger; F LaMotte; J M Gaziano; P M Ridker; W Willett; R Peto Journal: N Engl J Med Date: 1996-05-02 Impact factor: 91.245
Authors: Neval E Wareham; Qiuju Li; Henrik Sengeløv; Caspar Da Cunha-Bang; Finn Gustafsson; Carsten Heilmann; Michael Perch; Allan Rasmussen; Søren Schwartz Sørensen; Amanda Mocroft; Jens D Lundgren Journal: J Cancer Res Clin Oncol Date: 2019-11-05 Impact factor: 4.553