Genetic variation across C-reactive protein and risk of prostate cancer.
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.


CONCLUSIONS
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.
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
Sarah C
SC
Markt
Jennifer R
JR
Rider
Kathryn L
KL
Penney
Fredrick R
FR
Schumacher
Mara M
MM
Epstein
Katja
K
Fall
Howard D
HD
Sesso
Meir J
MJ
Stampfer
Lorelei A
LA
Mucci
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000032:analysis / Q000235:genetics*; D016022:Case-Control Studies; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood / Q000209:etiology / Q000235:genetics*; D012306:Risk
D002097:C-Reactive Protein
CRP SNPs; inflammation; prostate cancer