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Genetic variation across C‐reactive protein and risk of prostate cancer
Author(s) -
Markt Sarah C.,
Rider Jennifer R.,
Penney Kathryn L.,
Schumacher Fredrick R.,
Epstein Mara M.,
Fall Katja,
Sesso Howard D.,
Stampfer Meir J.,
Mucci Lorelei A.
Publication year - 2014
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22820
Subject(s) - prostate cancer , single nucleotide polymorphism , medicine , oncology , minor allele frequency , prostate , cancer , c reactive protein , prospective cohort study , genotype , snp , allele , case control study , biology , inflammation , genetics , gene
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. Prostate 74:1034–1042, 2014 . © 2014 Wiley Periodicals, Inc.