Genetic variation in C‐reactive protein in relation to colon and rectal cancer risk and survival

Slattery, Martha L.; Curtin, Karen; Poole, Elizabeth M.; Duggan, David; Samowitz, Wade S.; Peters, Ulrike; Caan, Bette J.; Potter, John D.; Ulrich, Cornelia M.

doi:10.1002/ijc.25721

Cited by 44 publications

(57 citation statements)

References 40 publications

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“…Another approach could be examining associations between CRP gene polymorphisms and colorectal cancer risk by using Mendelian principals that help to rule out residual confounding (78). In a recent population-based study with 2,365 colorectal cancer cases and 2,969 controls, genetic differences in the CRP gene variants influenced colon and rectal cancer risks as well as survival (79). Finally, clinical trials assessing use of NSAIDs in colorectal cancer could evaluate CRP as one of the markers to identify high-risk groups as well as to monitor treatment efficacy.…”

Section: Discussionmentioning

confidence: 99%

C-Reactive Protein and Colorectal Cancer Mortality in U.S. Adults

Goyal¹,

Terry

Jin

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Chronic inflammation has been associated with colorectal cancer. Prediagnostic levels of C-reactive protein (CRP), a highly sensitive marker of inflammation, have been weakly associated with increased colorectal cancer incidence, but few data are available examining its relationship with colorectal cancer mortality.Methods: In the Third National Health and Nutrition Examination Survey (NHANES III), 65% of the 15,924 adult participants had CRP levels 0.21 mg/dL. Using this as the reference group, we calculated hazard ratios (HR) for higher CRP categories and colorectal cancer mortality, and compared them with HRs for other mortality causes.Results: Over a median follow-up period of 14.2 years, there were 92 deaths from colorectal cancer. Compared with the reference group, multivariable adjusted HRs for colorectal cancer mortality were 2.66 [95% confidence interval (CI), 1.36-5.20] for CRP levels 0.22-0.50 mg/dL; 3.40 (95% CI, 1.48-7.77) for levels 0.51-1.00 mg/dL; and 3.96 (95% CI, 1.64-9.52) for levels >1.00 mg/dL. Estimates for colorectal cancer mortality did not change appreciably after excluding deaths within the first 3 years or by limiting follow-up to 5 or 10 years.Conclusions: In a large representative study of U.S. adults, we observed strong dose-response associations between CRP levels and colorectal cancer mortality.Impact: Further evaluation of CRP may help identify high-risk groups for colorectal cancer screening and those who might benefit most from prophylactic anti-inflammatory therapy. Cancer Epidemiol Biomarkers Prev; 23(8); 1609-18. Ó2014 AACR.

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Section: Discussionmentioning

confidence: 99%

C-Reactive Protein and Colorectal Cancer Mortality in U.S. Adults

Goyal¹,

Terry

Jin

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…In contrast, Poole et al also reporteddifferent CRP polymorphisms that were associated with increased risk of both adenomas and hyperplastic polyps(23). CRP gene polymorphisms have also been associated with the risk of CRC, and specificallyCPG-island methylator phenotype (CIMP) cancers (24). Given these findings, it is possible that heterogeneity of CRP alleleswithin the study population and the associated differences in CRP elevations and corresponding risk of polyps could explain our and other reported null associations between CRP levels and CRC precursors.…”

Section: Discussionmentioning

confidence: 99%

C-reactive Protein and Risk of Colorectal Adenomas or Serrated Polyps: A Prospective Study

Crockett

Mott

Barry

et al. 2014

Cancer Prevention Research

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Serum C-reactive protein (CRP) is a sensitive marker of systemic inflammation. Since there is a well-recognized relationship between local inflammation and colorectal cancer, we aimed to evaluate whether serum CRP levels were associated with the occurrence of colorectal adenomas and serrated polyps using data from a large adenoma prevention trial. 930 participants with a history of colorectal adenomas were enrolled in a randomized trial of calcium supplementation (1200 mg/day) for the prevention of colorectal adenomas. Outcomes in this analysis are metachronous adenomas (and advanced neoplasms specifically), and serrated polyps at follow-up colonoscopy. High sensitivity CRP levels were measured 1 year following baseline colonoscopy. Multivariate analysis was performed to estimate risk ratios (RR) using Poisson regression, controlling for potential confounders. We measured serum CRP levels in 689 participants(mean CRP 3.62mg/L ± 5.72). There was no difference in CRP levels with respect to calcium vs. placebo treatment assignment (p=0.99). After adjustment for potential confounders, we found no association between CRP level and risk of recurrent adenoma or advanced lesion (Quartile 4 vs. Quartile 1: RR (95% CI) = 0.99 (0.73, 1.34) and 0.92 (0.49, 1.75) respectively). Similarly, no association was seen between CRP levels and riskof serrated polypsor proximal serrated polyps(Quartile 4 vs. Quartile 1: RR (95% CI) = 1.32 (0.85, 2.03) and 1.19 (0.54, 2.58) respectively. In conclusion, this large prospective colorectal adenoma chemoprevention study found no significant relationship between CRP levels and occurrence of adenomas, advanced neoplasms, or serrated polyps.

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“…In situations of chronic underlying disease, however, CRP remains slightly raised over time, serving as a biomarker to characterize systemic inflammation 1, 2 . Elevated CRP levels have been associated with a large number of outcomes and traits, such as cardiovascular events 1, 2 , atherosclerosis 3 , stroke 4 , type 2 diabetes (T2D) 5 , fitness level and body composition 6 , and cancer 7, 8 . As such, serum CRP is an important biomarker for the presence or development of disease among apparently healthy individuals 1, 2 .…”

Section: Introductionmentioning

confidence: 99%

Multiancestral Analysis of Inflammation-Related Genetic Variants and C-Reactive Protein in the Population Architecture Using Genomics and Epidemiology Study

Kocarnik¹,

Pendergrass²,

Carty³

et al. 2014

Circ Cardiovasc Genet

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Background C-reactive protein (CRP) is a biomarker of inflammation. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with CRP concentrations and inflammation-related traits such as cardiovascular disease, type 2 diabetes, and obesity. We aimed to replicate previous CRP-SNP associations, assess whether these associations generalize to additional race/ethnicity groups, and evaluate inflammation-related SNPs for a potentially pleiotropic association with CRP. Methods and Results We selected and analyzed 16 CRP-associated and 250 inflammation-related GWAS SNPs among 40,473 African American, American Indian, Asian/Pacific Islander, European American, and Hispanic participants from 7 studies collaborating in the Population Architecture using Genomics and Epidemiology (PAGE) study. Fixed-effect meta-analyses combined study-specific race/ethnicity-stratified linear regression estimates to evaluate the association between each SNP and high-sensitivity CRP. Overall, 18 SNPs in 8 loci were significantly associated with CRP (Bonferroni-corrected p<3.1×10−3 for replication, p<2.0×10−4 for pleiotropy): Seven of these were specific to European Americans, while 9 additionally generalized to African Americans (1), Hispanics (5), or both (3); 1 SNP was seen only in African Americans and Hispanics. Two SNPs in the CELSR2/PSRC1/SORT1 locus showed a potentially novel association with CRP: rs599839 (p=2.0×10−6) and rs646776 (p=3.1×10−5). Conclusions We replicated 16 SNP-CRP associations, 10 of which generalized to African Americans and/or Hispanics. We also identified potentially novel pleiotropic associations with CRP for two SNPs previously associated with coronary artery disease and LDL cholesterol. These findings demonstrate the benefit of evaluating genotype-phenotype associations in multiple race/ethnicity groups, and of looking for pleiotropic relationships among SNPs previously associated with related phenotypes.

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Genetic variation in C‐reactive protein in relation to colon and rectal cancer risk and survival

Cited by 44 publications

References 40 publications

C-Reactive Protein and Colorectal Cancer Mortality in U.S. Adults

C-Reactive Protein and Colorectal Cancer Mortality in U.S. Adults

C-reactive Protein and Risk of Colorectal Adenomas or Serrated Polyps: A Prospective Study

Multiancestral Analysis of Inflammation-Related Genetic Variants and C-Reactive Protein in the Population Architecture Using Genomics and Epidemiology Study

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