Associations of circulating C-reactive protein and interleukin-6 with cancer risk: findings from two prospective cohorts and a meta-analysis.
ABSTRACT We investigated the associations of circulating C-reactive protein (CRP) and interleukin-6 (IL-6) with cancer risk.
We examined the associations of CRP and IL-6 with incident cancer in two prospective cohorts, the British Women's Heart and Health Study (4,286 women aged 60-80) and the Caerphilly Cohort (2,398 men aged 45-59) using Cox regression and pooled our findings with previous prospective studies' in fixed and random effects meta-analyses.
CRP and IL-6 were associated with some incident cancers in our cohorts, but the numbers of cancer cases were small. In our meta-analyses elevated CRP was associated with an increased overall risk of cancer (random effects estimate (RE): 1.10, 95% CI: 1.02, 1.18) and lung cancer (RE: 1.32, 95% CI: 1.08, 1.61). Its associations with colorectal (RE: 1.09, 95% CI: 0.98, 1.21) and breast cancer risks (RE: 1.10, 95% CI: 0.97, 1.26) were weaker. CRP appeared unrelated to prostate cancer risk (RE: 1.00 0.88, 1.13). IL-6 was associated with increased lung and breast cancer risks and decreased prostate cancer risk, and was unrelated to colorectal cancer risk.
Our findings suggest an etiological role for CRP and IL-6 in some cancers. Further large prospective and genetic studies would help to better understand this role.
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ABSTRACT: Self-rated health (SRH) is associated with risk for mortality, but its biological basis is poorly understood. We examined the association between SRH and low-grade inflammation in a Japanese general population. A total of 5142 men and 11,114 women aged 40 to 69years were enrolled. SRH was assessed by a single question and classified into four categories: good, rather good, neither good nor poor, and poor. Serum high-sensitivity C-reactive protein (hsCRP) levels were measured by the latex-enhanced immunonephelometric method. Elevated CRP was defined as hsCRP level of 1.0mg/L or higher. The association between SRH and elevated CRP was evaluated by using logistic regression with adjustment for age, socioeconomic status (job status, education and marital status), health-related behaviors (smoking status, drinking status, exercise habits and sleep duration), and cardiovascular risk factors (body mass index, systolic blood pressure, total- and HDL-cholesterol, HbA1c and prevalent stroke and/or myocardial infarction). Compared to persons with good SRH, persons with poor SRH had significantly higher risk for elevated CRP: age-adjusted ORs (95% CIs) were 1.33 (1.01-1.76) in men and 1.66 (1.36-2.02) in women. The significant association remained even after adjustment for socioeconomic status, health-related behaviors and cardiovascular risk factors in women, whereas the significance disappeared in men. Poor SRH is associated with low-grade inflammation in both sexes. In women, but not in men, the association is independent of potential confounders. These findings provide an insight into the biological background of SRH in a general population.Journal of psychosomatic research 09/2012; 73(3):225-31. DOI:10.1016/j.jpsychores.2012.05.013 · 2.84 Impact Factor
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ABSTRACT: To review findings from major epidemiologic studies regarding risk factors for and consequences of elevated markers of inflammation in older adults. Most large, current epidemiologic studies of older adults have measured serum interleukin-6 (IL-6), C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-alpha) and some studies also include more extensive batteries of measures including soluble receptors. There are few defined risk factors for the modest elevations in inflammatory markers seen with aging. These include visceral adiposity, lower sex steroid hormones, smoking, depression and periodontal disease. Of the markers assessed, IL-6 is most robustly associated with incident disease, disability and mortality. Though correlated with age, the etiology of elevated inflammatory markers remains incompletely defined. Inflammation, especially IL-6 may be a common cause of multiple age-related diseases or a final common pathway by which disease leads to disability and adverse outcomes in older adults. Future research targeting inflammation should examine these pathways.Ageing research reviews 12/2010; 10(3):319-29. DOI:10.1016/j.arr.2010.11.002 · 7.63 Impact Factor
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ABSTRACT: Chronic inflammation has been implicated in the pathogenesis of many chronic diseases, including colorectal cancer. Obesity has been identified as a risk factor for colorectal cancer via induction of a chronic state of low-grade bowel inflammation due to excessive release of inflammatory cytokines such as C-Reactive protein (CRP) by adipocytes. Prior studies have produced evidence of positive associations between CRP and colon cancer risk but none to date have assessed if elevated CRP is an independent risk factor when controlling for obesity. Also, controversy exists about which measure of adiposity best predicts risk of colon cancer. METHODS: We examined these questions using the National Health and Nutrition Examination Survey III (NHANES III) database linked to the National Death Index. In addition to CRP level, we studied the following four adiposity measures: body mass index, waist circumference, waist-to-hip ratio, and a new index developed by the NIH that stratifies BMI according to waist circumference. Outcome variables were: all-cause, colorectal cancer, other obesity related cancers, and all other causes. Dichotomous and Polytomous Logistic Regression were performed. RESULTS: CRP levels showed positive but weak correlations with adiposity measures. In the age-adjusted and multivariate Dichotomous Logistic Regression analyses, elevated CRP level was significantly associated with all-cause mortality (OR=1.63 95% CI 1.40-1.91; and OR=1.32, 95% CI 1.08-1.61; respectively.) Using age-adjusted and multivariate Polytomous Logistic Regression, elevated CRP level was associated with mortality from colorectal cancer (OR=2.72, 95% CI 1.30-5.72; OR= 2.44, 95% CI 1.20-4.94; respectively.) OR estimates did not change appreciably when adiposity measures were included in multivariate models. Further, none of the body measures of adiposity were significantly associated with cause-specific death in either age-adjusted or multivariate analyses. CONCLUSIONS: Our findings suggest that CRP may be an independent risk factor for all-cause and, more so, for colorectal cancer mortality. We speculate that the surprising effects related to body measures of adiposity may reflect misclassification related to the single baseline obesity measurement, taken during 1988-94, in light of the obesity epidemic that emerged during the follow-up time period. Further investigation of this relationship is warranted to determine of elevated CRP remains an independent risk factor when longitudinal adiposity history is known.