Elevated Plasma YKL-40 Predicts Increased Risk of Gastrointestinal Cancer and Decreased Survival After Any Cancer Diagnosis in the General Population

2009 ◽  
Vol 27 (4) ◽  
pp. 572-578 ◽  
Author(s):  
Julia S. Johansen ◽  
Stig E. Bojesen ◽  
Anne K. Mylin ◽  
Ruth Frikke-Schmidt ◽  
Paul A. Price ◽  
...  
Keyword(s):  
General Population ◽  
Cancer Diagnosis ◽  
Gastrointestinal Cancer ◽  
Early Death ◽  
Elevated Plasma ◽  
Hazard Ratios ◽  
Incident Cancer ◽  
Heart Study ◽  
Increased Risk ◽  
Risk Of Cancer

PurposeElevated plasma YKL-40 is a biomarker of poor prognosis in cancer patients. We tested the hypotheses that elevated plasma YKL-40 predicts risk of cancer as well as survival after a cancer diagnosis in the general population.Patients and MethodsA prospective cohort study of 8,899 subjects (20 to 95 years) from the Danish general population, the Copenhagen City Heart Study, observed for 11 years for cancer incidence and 14 years for death: 1,432 participants had a first incident cancer, 968 of these died. Hazard ratios (HRs) for cancer events and death after events according to plasma YKL-40 in sex and 10 years age percentile categories: 0% to 33%, 34% to 66%, 67% to 90%, 91% to 95%, and 96% to 100%.ResultsThe cumulative incidence of gastrointestinal cancer increased with increasing YKL-40 (trend P < .0001). Multifactorially adjusted HRs for gastrointestinal cancer were 1.0 (95% CI, 0.7 to 1.5) for YKL-40 in category 34% to 66%, 1.5 for 67% to 90% (95% CI, 1.0 to 2.3), 2.4 for 91% to 95%, (95% CI, 1.3 to 4.6), and 3.4 for 96% to 100% (95% CI, 1.9 to 6.1) versus YKL-40 category 0% to 33% (P < .0001). Participants with any cancer event and YKL-40 category 91% to 100% had a median survival time after the diagnosis of 1 year versus 4 years in participants with YKL-40 category 0% to 33% (P < .0001). Corresponding values for gastrointestinal cancer were 6 months versus 1 year (P = .007). Multifactorially adjusted HRs for early death were 1.8 (95% CI, 1.3 to 2.5; P < .0001) after any cancer and 2.4 (95% CI, 1.3 to 4.3; P = .005) after gastrointestinal cancer in participants with YKL-40 category 91% to 100% versus 0% to 33%.ConclusionIn the general population, elevated plasma YKL-40 predicts increased risk of gastrointestinal cancer and decreased survival after any cancer diagnosis.

Association of baseline c-reactive protein with incident cancer and survival in cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11052-11052
Author(s):  
K. H. Allin ◽  
S. E. Bojesen ◽  
B. G. Nordestgaard
Keyword(s):  
Colorectal Cancer ◽  
Lung Cancer ◽  
General Population ◽  
Cancer Patients ◽  
Early Death ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Hazard Ratios ◽  
Incident Cancer

11052 Background: We tested the hypothesis that baseline plasma levels of C-reactive protein (CRP) associate with risk of incident cancer in the general population, and early death in cancer patients. Methods: 10,408 individuals from the Danish general population, who had CRP measured at baseline, were followed for up to 16 years; 1,624 developed cancer and of these, 998 died during follow-up. Follow-up was 100% complete. We excluded individuals with a cancer diagnosis at baseline. Results: Baseline CRP levels >3 vs. <1 mg/L were associated with multifactorially adjusted hazard ratios of 1.3 (95% CI, 1.0–1.6) for cancer of any type, of 2.2 (1.0–4.6) for lung cancer, of 1.9 (0.8–4.6) for colorectal cancer, and of 0.7 (0.4–1.4) for breast cancer. Corresponding hazard ratios for the highest vs. the lowest quintile of baseline CRP levels were 1.3 (1.0–1.6), 2.1 (1.2–3.8), 1.7 (0.8–3.2), and 0.9 (0.5–1.7), respectively. Multifactorially adjusted hazard ratios for early death in cancer patients were 1.8 (1.2–2.7) for CRP >3 vs. <1 mg/L and 1.4 (1.1–1.7) for the highest vs. the lowest quintile. Elevated CRP levels associated with early death in cancer patients with localized disease, but not in cancer patients with metastases (interaction; P=.03). Conclusions: Elevated levels of CRP in cancer-free individuals are associated with increased risk of cancer of any type, of lung cancer, and possibly of colorectal cancer. Moreover, elevated levels of baseline CRP associate with early death after a diagnosis of any cancer, particularly in patients without metastases. No significant financial relationships to disclose.

scholarly journals Plasma YKL-40 and Total and Disease-Specific Mortality in the General Population

2010 ◽  
Vol 56 (10) ◽  
pp. 1580-1591 ◽  
Author(s):  
Julia S Johansen ◽  
Stig E Bojesen ◽  
Anne Tybjærg-Hansen ◽  
Anne K Mylin ◽  
Paul A Price ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
General Population ◽  
Early Death ◽  
Mortality Rates ◽  
Term Survival ◽  
Hazard Ratios ◽  
Heart Study ◽  
Specific Mortality ◽  
Disease Specific Mortality ◽  
Disease Specific

BACKGROUND Increased plasma YKL-40 is associated with short-term survival in patients with cardiovascular disease and cancer. We tested the hypothesis that increased plasma YKL-40 is associated with total and disease-specific mortality in the general population. METHODS We measured plasma YKL-40 in 8899 study participants, aged 20–95 years, in the Copenhagen City Heart Study from the Danish general population who were followed for 16 years: 3059 died, 2158 had ischemic cardiovascular disease, 2271 had cancer, and 2820 had other diseases associated with increased YKL-40. Hazard ratios for early death and absolute 10-year mortality rates were calculated according to plasma YKL-40 percentile groupings computed within sex and age decade: 0%–33%, 34%–66%, 67%–90%, 91%–95%, and 96%–100%. RESULTS Median survival age decreased from 83 years for participants with plasma YKL-40 in category 0%–33% to 69 years in category 96%–100% (trend, P &lt; 0.0001). Risk of early death was increased (multifactorially adjusted hazard ratios) by 10% for YKL-40 category 34%–66%, by 30% for 67%–90%, by 70% for 91%–95%, and by 90% for 96%–100% vs YKL-40 category 0%–33% (trend, P &lt; 0.0001). Corresponding increases in participants with ischemic cardiovascular disease were 10%, 20%, 80%, and 60% (P &lt; 0.0001); in those with cancer were 10%, 20%, 50%, and 70% (P &lt; 0.0001); and in those with other diseases were 10%, 20%, 40%, and 60% (P &lt; 0.0001). Highest absolute 10-year mortality rates were 78% and 90% in women and men, respectively, who were &gt;70 years old, smoked, and were in YKL-40 category 96%–100%. CONCLUSIONS Increased plasma YKL-40 is associated with risk of early death from cardiovascular disease, cancer, and other diseases in the general population.

scholarly journals Serum Soluble CD163 Predicts Risk of Type 2 Diabetes in the General Population

2011 ◽  
Vol 57 (2) ◽  
pp. 291-297 ◽  
Author(s):  
Holger J Møller ◽  
Ruth Frikke-Schmidt ◽  
Søren K Moestrup ◽  
Børge G Nordestgaard ◽  
Anne Tybjærg-Hansen
Keyword(s):  
Type 2 Diabetes ◽  
General Population ◽  
Low Grade ◽  
Reactive Protein ◽  
Soluble Cd163 ◽  
Hazard Ratios ◽  
Heart Study ◽  
Increased Risk ◽  
Study Participants

BACKGROUND Activation of adipose tissue macrophages with concomitant low-grade inflammation is believed to play a central role in the development of type 2 diabetes. We tested whether a new macrophage-derived biomarker, soluble CD163 (sCD163), identifies at-risk individuals before overt disease has developed. METHODS A prospective cohort study of 8849 study participants from the general population, the Copenhagen City Heart Study, was followed for 18 years for incidence of type 2 diabetes. Risk of disease was calculated according to age- and sex-adjusted percentile categories of serum sCD163 concentrations: 0%–33%, 34%–66%, 67%–90%, 91%–95%, and 96%–100%. RESULTS A total of 568 participants developed type 2 diabetes. The cumulative incidence increased with increasing baseline sCD163 (trend P &lt; 0.001), and sCD163 was strongly associated with known risk factors such as physical inactivity, body mass index, C-reactive protein, and triglycerides (all P &lt; 0.001). Multifactorially adjusted hazard ratios for type 2 diabetes were 1.4 (95% CI, 1.0–1.9), 2.4 (1.8–3.2), 3.8 (2.6–5.5), and 5.2 (3.6–7.6) for categories 34%–66%, 67%–90%, 91%–95%, and 96%–100%, respectively, vs the 0%–33% category. In overweight men 50–70 and &gt;70 years of age, serum sCD163 concentrations in the top 5% group predicted an absolute 10-year risk of type 2 diabetes of 29% and 36% vs 7% and 8% in the lowest percentile group. Equivalent values in women were 19% and 24% vs 4% and 5%. CONCLUSIONS Increased concentrations of sCD163 predict increased risk of type 2 diabetes in the general population and may be useful for identification of high-risk overweight individuals.

Abstract 3603: Extreme Lipoprotein(a) Levels Predict a 3–4 Fold Increase in Risk of Myocardial Infarction in the General Population

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Pia R Kamstrup ◽  
Marianne Benn ◽  
Anne Tybjćrg Hansen ◽  
Børge G Nordestgaard
Keyword(s):  
Myocardial Infarction ◽  
General Population ◽  
Fold Increase ◽  
Threshold Effect ◽  
Lipoprotein A ◽  
Hazard Ratios ◽  
Heart Study ◽  
Increased Risk ◽  
Increase In Risk

Background: Elevated lipoprotein(a) levels associate with increased risk of myocardial infarction in some, but not all studies. Limitations of previous studies include lack of risk estimates for extreme lipoprotein(a) levels, measurements in long-term frozen samples and no correction for regression dilution bias. We tested the hypothesis that extreme lipoprotein(a) levels predict myocardial infarction in the general population, measuring levels shortly after sampling and correcting for regression dilution bias. Methods and Results: We examined 9330 men and women from the Danish general population, The Copenhagen City Heart Study. During 10 years follow-up, 498 participants developed myocardial infarction. In women, multifactorially adjusted hazard ratios for myocardial infarction for elevated lipoprotein(a) levels were 1.1(95% confidence interval 0.6 –1.9) for 5–29 mg/dL, 1.7(1.0 –3.1) for 30 – 84 mg/dL, 2.6(1.2–5.9) for 85–119 mg/dL (>90 th percentile), and 3.6(1.7–7.7) for ≥120 mg/dL (>95 th percentile) versus levels <5 mg/dL (figure , p-values are test for trend of hazard ratios). Equivalent values in men were 1.5(0.9 –2.3), 1.6(1.0 –2.6), 2.6(1.2–5.5), and 3.7(1.7– 8.0). Conclusions: We observed a stepwise increase in risk of myocardial infarction with increasing levels of lipoprotein(a) in both genders, with no evidence of a threshold effect. Extreme lipoprotein(a) levels predict a 3– 4 fold increase in risk of myocardial infarction in the general population. Figure. Risk of myocardial infarction by levels of lipoprotein(a)

scholarly journals Complement C3 and Risk of Diabetic Microvascular Disease: A Cohort Study of 95202 Individuals from the General Population

2018 ◽  
Vol 64 (7) ◽  
pp. 1113-1124 ◽  
Author(s):  
Katrine Laura Rasmussen ◽  
Børge Grønne Nordestgaard ◽  
Sune Fallgaard Nielsen
Keyword(s):  
Diabetic Retinopathy ◽  
General Population ◽  
Microvascular Disease ◽  
Complement C3 ◽  
General Population Study ◽  
Hazard Ratios ◽  
Genome Wide ◽  
Heart Study ◽  
Increased Risk ◽  
High Concentrations

Abstract BACKGROUND Whether the complement system is involved in the development of diabetic microvascular disease is unknown. We tested the hypothesis that high concentrations of complement C3 are associated with increased risk of diabetic retinopathy, nephropathy, and neuropathy in individuals from the general population. METHODS We studied 95202 individuals from the general population with baseline measurements of complement C3, genotyped for rs1065489, rs429608, and rs448260 determining concentrations of complement C3, and enrolled in the Copenhagen General Population Study from 2003 through 2013, following them until April 10, 2013. Rs1065489, rs429608, and rs448260 were identified with genome-wide association scans in 3752 individuals from the Copenhagen City Heart Study. RESULTS The cumulative incidence was increased from the lowest tertile to the highest tertile of complement C3 for diabetic retinopathy (log-rank trend, P = 1 × 10−20), nephropathy (P = 7 × 10−15), and neuropathy (P = 5 × 10−10). Multifactorially adjusted hazard ratios for a 1 SD higher concentration of complement C3 were 1.87 (95% CI, 1.61–2.18) for diabetic retinopathy, 1.90 (1.62–2.23) for diabetic nephropathy, and 1.56 (1.29–1.89) for diabetic neuropathy. The multifactorially adjusted hazard ratio for individuals with the highest vs lowest tertile of complement C3 was 3.29 (1.78–6.07) for retinopathy, 2.71 (1.42–5.16) for nephropathy, and 2.40 (1.26–4.54) for neuropathy. CONCLUSIONS High baseline concentrations of complement C3 were associated with increased risk of diabetic retinopathy, nephropathy, and neuropathy in individuals from the general population. These epidemiological findings were substantiated by a Mendelian randomization approach, potentially indicating causality.

Baseline C-Reactive Protein Is Associated With Incident Cancer and Survival in Patients With Cancer

2009 ◽  
Vol 27 (13) ◽  
pp. 2217-2224 ◽  
Author(s):  
Kristine H. Allin ◽  
Stig E. Bojesen ◽  
Børge G. Nordestgaard
Keyword(s):  
Colorectal Cancer ◽  
Lung Cancer ◽  
General Population ◽  
Early Death ◽  
C Reactive Protein ◽  
Patients With Cancer ◽  
Reactive Protein ◽  
Hazard Ratios ◽  
Incident Cancer

Purpose We tested the hypothesis that baseline plasma levels of C-reactive protein (CRP) are associated with risk of incident cancer in the general population and early death in patients with cancer. Patients and Methods A total of 10,408 individuals from the Danish general population who had CRP measured at baseline were observed for up to 16 years; 1,624 developed cancer, and of these, 998 patients died during follow-up. Follow-up was 100% complete. We excluded individuals with a cancer diagnosis at baseline. Results Baseline CRP levels more than 3 versus less than 1 mg/L were associated with multifactorially adjusted hazard ratios of 1.3 (95% CI, 1.0 to 1.6) for cancer of any type, 2.2 (95% CI, 1.0 to 4.6) for lung cancer, 1.9 (95% CI, 0.8 to 4.6) for colorectal cancer, and 0.7 (95% CI, 0.4 to 1.4) for breast cancer. Corresponding hazard ratios for the highest versus the lowest quintile of baseline CRP levels were 1.3 (95% CI, 1.0 to 1.6), 2.1 (95% CI, 1.2 to 3.8), 1.7 (95% CI, 0.8 to 3.2), and 0.9 (95% CI, 0.5 to 1.7), respectively. Multifactorially adjusted hazard ratios for early death in patients with cancer were 1.8 (95% CI, 1.2 to 2.7) for CRP more than 3 versus less than 1 mg/L and 1.4 (95% CI, 1.1 to 1.7) for the highest versus the lowest quintile. Elevated CRP levels were associated with early death in patients with cancer having localized disease, but not in those with metastases (interaction; P = .03). Conclusion Elevated levels of CRP in cancer-free individuals are associated with increased risk of cancer of any type, of lung cancer, and possibly of colorectal cancer. Moreover, elevated levels of baseline CRP associate with early death after a diagnosis of any cancer, particularly in patients without metastases.

scholarly journals Cancer mortality in patients with schizophrenia: systematic review and meta-analysis

2017 ◽  
Vol 211 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Chuanjun Zhuo ◽  
Ran Tao ◽  
Ronghuan Jiang ◽  
Xiaodong Lin ◽  
Mingjing Shao
Keyword(s):  
Systematic Review ◽  
General Population ◽  
Cancer Mortality ◽  
Meta Analysis ◽  
The Other ◽  
Random Effects Model ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Standardised Mortality Ratios ◽  
Risk Of Cancer

BackgroundPrevious studies have reported conflicting results on the association between schizophrenia and cancer mortality.AimsTo summarise available evidence and quantify the association between schizophrenia and cancer mortality using meta-analysis.MethodWe systematically searched literature in the PubMed and Embase databases. Risk estimates and 95% confidence intervals reported in individual studies were pooled using the DerSimonian–Laird random-effects model.ResultsWe included 19 studies in the meta-analysis. Among them, 15 studies reported standardised mortality ratios (SMRs) comparing patients with schizophrenia with the general population, and the pooled SMR was 1.40 (95% CI 1.29–1.52, P<0.001). The other four studies reported hazard ratios (HRs) comparing individuals with schizophrenia with those without schizophrenia; the pooled HR was 1.51 (95% CI 1.13–2.03, P = 0.006).ConclusionsPatients with schizophrenia are at a significantly increased risk of cancer mortality compared with the general population or individuals without schizophrenia.

Risk of Cancer by ATM Missense Mutations in the General Population

2008 ◽  
Vol 26 (18) ◽  
pp. 3057-3062 ◽  
Author(s):  
Sarah Louise Dombernowsky ◽  
Maren Weischer ◽  
Kristine Højgaard Allin ◽  
Stig Egil Bojesen ◽  
Anne Tybjjrg-Hansen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
General Population ◽  
Cancer Susceptibility ◽  
Endocrine Tumors ◽  
Missense Mutations ◽  
Cancer Subtypes ◽  
Corpus Uteri ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Risk Of Cancer

Purpose Truncating and missense mutations in the ATM gene, which cause insufficient DNA damage surveillance, allow damaged cells to proceed into mitosis, which eventually results in increased cancer susceptibility. We tested the hypotheses that ATM Ser49Cys and ATM Ser707Pro heterozygosity increase the risk of cancer overall, of breast cancer, and of 26 other cancer subtypes in the general population. Patients and Methods We genotyped 10,324 individuals from the Danish general population who were observed prospectively for 36 years, during which 2,056 developed cancer. Results Multifactorially adjusted hazard ratios for ATM Ser49Cys heterozygotes versus noncarriers were 1.2 (95% CI, 0.9 to 1.5) for cancer overall, 0.8 (95% CI, 0.3 to 2.0) for breast cancer, 4.8 (95% CI, 2.2 to 11) for melanoma, 2.3 (95% CI, 1.1 to 5.0) for prostate cancer, and 3.4 (95% CI, 1.1 to 11) for cancer of the oral cavity/pharynx. Multifactorially adjusted hazard ratios for ATM Ser707Pro heterozygotes versus noncarriers were 0.8 (95% CI, 0.6 to 1.2) for cancer overall, 0.6 (95% CI, 0.2 to 1.6) for breast cancer, 10 (95% CI, 1.1 to 93) for thyroid/other endocrine tumors, and 2.7 (95% CI, 1.0 to 7.6) for cancer of corpus uteri. Conclusion ATM missense mutations do not increase the risk of cancer overall or of breast cancer in the general population; however, we observed in exploratory analyses that ATM missense mutations may be associated with an increased risk of other cancer subtypes. As we did multiple comparisons, some of these findings could represent chance findings rather than real phenomena.

scholarly journals Total and Cause-Specific Mortality by Moderately and Markedly Increased Ferritin Concentrations: General Population Study and Metaanalysis

2014 ◽  
Vol 60 (11) ◽  
pp. 1419-1428 ◽  
Author(s):  
Christina Ellervik ◽  
Jacob Louis Marott ◽  
Anne Tybjærg-Hansen ◽  
Peter Schnohr ◽  
Børge G Nordestgaard
Keyword(s):  
General Population ◽  
Total Mortality ◽  
Early Death ◽  
Premature Death ◽  
Population Based ◽  
General Population Study ◽  
Ferritin Concentration ◽  
Heart Study ◽  
Increased Risk ◽  
Specific Mortality

Abstract BACKGROUND Previous population-based studies of plasma ferritin concentration have not revealed a relationship with total mortality. We tested the possible association of increased ferritin concentrations with increased risk of total and cause-specific mortality in the general population. METHODS We examined total and cause-specific mortality according to baseline plasma ferritin concentrations in a Danish population–based study (the Copenhagen City Heart Study) of 8988 individuals, 6364 of whom died (median follow-up 23 years). We also included a metaanalysis of total mortality comprising population-based studies according to ferritin quartiles or tertiles. RESULTS Multifactorially adjusted hazard ratios (HRs) for total mortality for individuals with ferritin ≥200 vs &lt;200 μg/L were 1.1 (95% CI 1.1–1.2; P = 0.0008) overall, 1.1 (1.0–1.2; P = 0.02) in men, and 1.2 (1.0–1.3; P = 0.03) in women. Stepwise increasing concentrations of ferritin were associated with a stepwise increased risk of premature death overall (log rank, P = 2 × 10−22), with median survival of 55 years at ferritin concentrations ≥600 μg/L, 72 years at 400–599 μg/L, 76 years at 200–399 μg/L, and 79 years at ferritin &lt;200 μg/L. The corresponding HR for total overall mortality for ferritin ≥600 vs &lt;200 μg/L was 1.5 (1.2–1.8; P = 0.00008). Corresponding adjusted HRs for ferritin ≥600 vs &lt;200 μg/L were 1.6 (1.1–2.3; P = 0.01) for cancer mortality, 2.9 (1.7–5.0; P = 0.0001) for endocrinological mortality, and 1.5 (1.1–2.0; P = 0.01) for cardiovascular mortality. The metaanalysis random effects odds ratio for total mortality for ferritin upper vs reference quartile or tertile was 1.0 (0.9–1.1; P = 0.3) (P heterogeneity = 0.5). CONCLUSIONS Moderately to markedly increased ferritin concentrations represent a biological biomarker predictive of early death in a dose-dependent linear manner in the general population.

scholarly journals Antihypertensive Drugs and the Risk of Cancer: A Nationwide Cohort Study

2021 ◽  
Vol 10 (4) ◽  
pp. 771
Author(s):  
In-Jeong Cho ◽  
Jeong-Hun Shin ◽  
Mi-Hyang Jung ◽  
Chae Young Kang ◽  
Jinseub Hwang ◽  
...  
Keyword(s):  
Antihypertensive Drugs ◽  
Beta Blockers ◽  
Angiotensin Receptor Blockers ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Channel Blockers ◽  
Antihypertensive Medications ◽  
Converting Enzyme Inhibitors ◽  
Incident Cancer ◽  
Increased Risk ◽  
Risk Of Cancer

We sought to assess the association between common antihypertensive drugs and the risk of incident cancer in treated hypertensive patients. Using the Korean National Health Insurance Service database, the risk of cancer incidence was analyzed in patients with hypertension who were initially free of cancer and used the following antihypertensive drug classes: Angiotensin-converting enzyme inhibitors (ACEIs); angiotensin receptor blockers (ARBs); beta blockers (BBs); calcium channel blockers (CCBs); and diuretics. During a median follow-up of 8.6 years, there were 4513 (6.4%) overall cancer incidences from an initial 70,549 individuals taking antihypertensive drugs. ARB use was associated with a decreased risk for overall cancer in a crude model (hazard ratio (HR): 0.744, 95% confidence interval (CI): 0.696–0.794) and a fully adjusted model (HR: 0.833, 95% CI: 0.775–0.896) compared with individuals not taking ARBs. Other antihypertensive drugs, including ACEIs, CCBs, BBs, and diuretics, did not show significant associations with incident cancer overall. The long-term use of ARBs was significantly associated with a reduced risk of incident cancer over time. The users of common antihypertensive medications were not associated with an increased risk of cancer overall compared to users of other classes of antihypertensive drugs. ARB use was independently associated with a decreased risk of cancer overall compared to other antihypertensive drugs.

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