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Plasma C-reactive protein, genetic risk score, and risk of common cancers in the Atherosclerosis Risk in Communities study.

ABSTRACT: 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.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.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.The study corroborates a causative role of chronic low-grade inflammation in colorectal carcinogenesis.

SUBMITTER: Prizment AE

PROVIDER: S-EPMC3836434 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Plasma C-reactive protein, genetic risk score, and risk of common cancers in the Atherosclerosis Risk in Communities study.

Prizment Anna E AE Folsom Aaron R AR Dreyfus Jill J Anderson Kristin E KE Visvanathan Kala K Joshu Corinne E CE Platz Elizabeth A EA Pankow James S JS

Cancer causes & control : CCC 20130914 12

<h4>Purpose</h4>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 ...[more]

PMID: 24036889

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Project description:The Atherosclerosis Risk in Communities (ARIC) Study, sponsored by the National Heart, Lung and Blood Institute (NHLBI), is a prospective epidemiologic study conducted in four U.S. communities. The four communities are Forsyth County, NC; Jackson, MS; the northwest suburbs of Minneapolis, MN; and Washington County, MD. ARIC is designed to investigate the etiology and natural history of atherosclerosis, the etiology of clinical atherosclerotic diseases, and variation in cardiovascular risk factors, medical care and disease by race, gender, location, and date. ARIC includes two parts: the Cohort Component and the Community Surveillance Component. The Cohort Component began in 1987, and each ARIC field center randomly selected and recruited a cohort sample of approximately 4,000 individuals aged 45-64 from a defined population in their community. A total of 15,792 participants received an extensive examination, including medical, social, and demographic data. These participants were reexamined every three years with the first screen (baseline) occurring in 1987-89, the second in 1990-92, the third in 1993-95, and the fourth and last exam was in 1996-98. Follow-up occurs yearly by telephone to maintain contact with participants and to assess health status of the cohort. In the Community Surveillance Component, currently ongoing, these four communities are investigated to determine the community-wide occurrence of hospitalized myocardial infarction and coronary heart disease deaths in men and women aged 35-84 years. Hospitalized stroke is investigated in cohort participants only. Starting in 2006, the study conducts community surveillance of inpatient (ages 55 years and older) and outpatient heart failure (ages 65 years and older) for heart failure events beginning in 2005. ARIC is currently funded through January 31, 2012. This study is part of the Gene Environment Association Studies initiative (GENEVA, <a href="http://www.genevastudy.org" target="_blank">http://www.genevastudy.org</a>) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to atherosclerosis and cardiovascular disease through large-scale genome-wide association studies of well-characterized cohorts of adults in four defined populations. Genotyping was performed at the Broad Institute of MIT and Harvard, a GENEVA genotyping center. Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.

Project description:Backgroundand ObjectivesHigher scores in Life's Simple 7 (LS7), a metric for cardiovascular and brain health, have been associated with lower risk of dementia. It is uncertain whether this association holds among those with high genetic risk of dementia. Our objective is to evaluate the extent that LS7 may offset dementia risk across the range of genetic risk.Methods PARTICIPANTS: in the Atherosclerosis Risk in Communities (ARIC) Study were followed from 1987-89 to 2019. We derived midlife LS7 scores and generated genetic risk scores (GRS) using genome-wide summary statistics of Alzheimer's Disease, which have been used to study the genetic risk for dementia. Incident dementia was ascertained based on the criteria of the National Institute on Aging-Alzheimer's Association workgroups and Diagnostic and Statistical Manual of Mental Disorders. The associations of the GRS and LS7 with incident dementia were evaluated using Cox regression.ResultsThis study included 8,823 European Americans (EA) and 2,738 African Americans (AA) (mean age at baseline: 54). We observed 1,603 cases of dementia among EA and 631 among AA (median follow-up: 26.2 years). Higher GRS were associated with higher risk of dementia (EA, hazard ratio [HR] per standard deviation [SD] 1.44, 95% confidence interval [CI]: 1.37, 1.51; AA, HR 1.26, 95% CI: 1.16, 1.36). Among EA, higher LS7 scores were consistently associated with lower risk of dementia across quintiles of GRS, including the highest quintile (HR per point 0.91, 95% CI: 0.87, 0.96). Among AA, the associations between LS7 and incident dementia within stratum of GRS had the same direction as among EA, though wide confidence intervals and smaller sample sizes limited reliable inferences.ConclusionsAcross strata of GRS, higher midlife LS7 scores were associated with lower risk of dementia. Larger sample sizes from diverse populations are needed to obtain more reliable estimates of the effects of modifiable health factors on dementia risk within genetic risk stratum in each ancestry group.

Dataset Information

Plasma C-reactive protein, genetic risk score, and risk of common cancers in the Atherosclerosis Risk in Communities study.

Publications

Plasma C-reactive protein, genetic risk score, and risk of common cancers in the Atherosclerosis Risk in Communities study.

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