title: Plasma C-reactive protein, genetic risk score, and risk of common cancers in the Atherosclerosis Risk in Communities study.
abstract: OBJECTIVE
  Many studies, including the Atherosclerosis Risk in Communities (ARIC) cohort, reported a positive association between plasma C-reactive protein (CRP)-a biomarker of low-grade chronic inflammation-and colorectal cancer risk, although it is unclear whether the association is causal. Our aims were to assess the associations of a CRP genetic risk score (CRP-GRS) created from single-nucleotide polymorphisms (SNPs) with colorectal cancer risk, as well as examine plasma CRP and CRP-GRS in relation to common cancers in the ARIC cohort.
  
  
  METHODS
  Cox proportional hazards models were used to prospectively estimate hazard ratios (HRs) and 95 % confidence interval (95 % CI) of total, colorectal, lung, prostate, and breast cancers in relation to: (1) CRP-GRS among 8,657 Whites followed in 1987-2006 and (2) log-transformed plasma CRP among 7,603 Whites followed in 1996-2006. A weighted CRP-GRS was comprised of 20 CRP-related SNPs located in/near CRP, APOC1, HNF1A, LEPR, and 16 other genes that were identified in genome-wide association studies.
  
  
  RESULTS
  After multivariable adjustment, one standard deviation increment of the CRP-GRS was associated with colorectal cancer risk (HR 1.19; 95 % CI 1.03-1.37), but not with any other cancer. One unit of log-transformed plasma CRP was associated with the risk of total, colorectal, lung, and breast cancers: HRs (95 % CIs) were 1.08 (1.01-1.15), 1.24 (1.01-1.51), 1.29 (1.08-1.54), and 1.27 (1.07-1.51), respectively. HRs remained elevated, although lost statistical significance for all but breast cancer, after excluding subjects with <2 years of follow-up.
  
  
  CONCLUSIONS
  The study corroborates a causative role of chronic low-grade inflammation in colorectal carcinogenesis.
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 2nd Street South, Suite 300, Minneapolis, MN, 55455, USA, prizm001@umn.edu.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Prizment
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.forename: Jill
authors.initials: J
authors.lastname: Dreyfus
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Anderson
authors.forename: Kala
authors.initials: K
authors.lastname: Visvanathan
authors.forename: Corinne E
authors.initials: CE
authors.lastname: Joshu
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
mesh_terms: D001741:Black or African American / Q000235:genetics*; D050197:Atherosclerosis / Q000097:blood / Q000150:complications* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis*; D002097:C-Reactive Protein / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000209:etiology*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D044465:White People / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D002097:C-Reactive Protein
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