Dataset Information

A prospective study of circulating adipokine levels and risk of multiple myeloma.

ABSTRACT: It has been hypothesized that the observed excess risk of multiple myeloma (MM) among obese persons could be the result of altered circulating levels of adipokines, polypeptide hormones with pro- and anti-inflammatory properties secreted by adipose tissue. We investigated whether circulating levels of leptin, total adiponectin, and high molecular weight adiponectin are associated with subsequent MM risk among 174 MM patients and 348 controls within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Inverse associations with MM were observed for total adiponectin (highest quartile vs lowest: odds ratio = 0.49; 95% CI = 0.26-0.93, P(trend) = .03) and high molecular weight adiponectin (0.44; 0.23-0.85, P(trend) = .01). These associations remained after restricting to MM patients diagnosed ? 8 years or more after blood collection. Leptin levels were not associated with MM risk. The results of this study, to our knowledge the first prospective investigation of circulating adipokines and MM, suggest that adiponectin may play an important role in obesity-related myelomagenesis.

SUBMITTER: Hofmann JN

PROVIDER: S-EPMC3507148 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A prospective study of circulating adipokine levels and risk of multiple myeloma.

Hofmann Jonathan N JN Liao Linda M LM Pollak Michael N MN Wang Ye Y Pfeiffer Ruth M RM Baris Dalsu D Andreotti Gabriella G Lan Qing Q Landgren Ola O Rothman Nathaniel N Purdue Mark P MP

Blood 20120924 22

It has been hypothesized that the observed excess risk of multiple myeloma (MM) among obese persons could be the result of altered circulating levels of adipokines, polypeptide hormones with pro- and anti-inflammatory properties secreted by adipose tissue. We investigated whether circulating levels of leptin, total adiponectin, and high molecular weight adiponectin are associated with subsequent MM risk among 174 MM patients and 348 controls within the Prostate, Lung, Colorectal, and Ovarian Can ...[more]

PMID: 23007407

Similar Datasets

Project description:Background: Several observational studies have demonstrated that significantly rising circulating adipokine levels are pervasive in preeclampsia or eclampsia disorder (or preeclampsia toxemia (PET)). However, it remains unclear whether this relationship is causal. In this study, we sought to elucidate the causal effects of circulating adipokine levels on PET. Methods: Summary-level data and independent genetic variants strongly associated with common adipokine molecule (adiponectin, leptin, resistin, sOB-R, and PAI-1) levels were drawn from public genome-wide association study (GWASs). Additionally, the corresponding effects between instrumental variables and PET outcomes were acquired from the FinnGen consortium, including 4,743 cases and 136,325 controls of European ancestry. Subsequently, an inverse-variance weighted (IVW) approach was applied for the principal two-sample Mendelian randomization (MR) and multivariable MR (MVMR) analyses. Various complementary sensitivity analyses were then carried out to determine the robustness of our models. Results: The results of the IVW method did not reveal any causal relationship shared across genetically predisposed adipokine levels and PET risk (for adiponectin, OR = 0.86, 95% CI: 0.65-1.13, p = 0.274). Additionally, no significant associations were identified after taking into account five circulating adipokines in MVMR research. Complementary sensitivity analysis also supported no significant associations between them. In the reverse MR analysis, genetically predicted PET risk showed a suggestive association with elevating PAI-1 levels by the IVW method (Beta = 0.120, 95% CI: 0.014, 0.227, p = 0.026). Furthermore, there were no strong correlations between genetic liability to PET and other adipokine levels (p > 0.05). Conclusion: Our MR study did not provide robust evidence supporting the causal role of common circulating adipokine levels in PET, whereas genetically predicted PET may instrumentally affect PAI-1 levels. These findings suggest that PAI-1 may be a useful biomarker for monitoring the diagnosis or therapy of PET rather than a therapeutic target for PET.

Project description:BackgroundExperimental and clinical studies have implicated certain chemokines and angiogenic cytokines in multiple myeloma (MM) pathogenesis. To investigate whether systemic concentrations of these markers are associated with future MM risk and progression from its precursor, monoclonal gammopathy of undetermined significance (MGUS), we conducted a prospective study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.MethodsWe measured concentrations of 45 immunologic and pro-angiogenic markers in sera from 241 MM case patients, 441 participants with nonprogressing MGUS, and 258 MGUS-free control participants using Luminex-based multiplex assays and enzyme-linked immunosorbent assays. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. We also evaluated absolute risk of progression using weighted Kaplan-Meier estimates. All statistical tests were two-sided.ResultsPrediagnostic levels of six markers were statistically significantly elevated among MM case patients compared with MGUS-free control participants using a false discovery rate of 10% (EGF, HGF, Ang-2, CXCL12, CCL8, and BMP-9). Of these, three angiogenesis markers were associated with future progression from MGUS to MM: EGF (fourth vs first quartile: OR?=?3.01, 95% CI = 1.61 to 5.63, P trend = .00028), HGF (OR = 2.59, 95% CI = 1.33 to 5.03, P trend = .015), and Ang-2 (OR = 2.14, 95% CI = 1.15 to 3.98, P trend = .07). A composite angiogenesis biomarker score substantially stratified risk of MGUS progression to MM beyond established risk factors for progression, particularly during the first 5?years of follow-up (areas under the curve of 0.71 and 0.64 with and without the angiogenesis marker score, respectively).ConclusionsOur prospective findings provide new insights into mechanisms involved in MM development and suggest that systemic angiogenesis markers could potentially improve risk stratification models for MGUS patients.

Project description:BackgroundAssociations of obesity and obesity-related metabolic factors (adiposity factors) with uterine corpus cancer (UCC) and ovarian cancer (OVC) risk have been described. Still, a cause-effect relationship and the underlying mediators remain unclear, particularly for low-incidence populations. We aimed to prospectively determine whether adiposity factors could predict the development of UCC and OVC in Taiwanese women. To explore the biological mediators linking adiposity factors to cancer risk, we examined the association of two adipokines, leptin and adiponectin, with the gynecological cancers.MethodsTotally, 11,258 women, aged 30-65, were recruited into the Community-Based Cancer Screening Program (CBCSP) study during 1991-1993, and were followed for UCC and OVC cases until December 31, 2011. Cox proportional hazard models were used to estimate hazard ratios (HRs). Adiposity factors and risk covariates were assessed at recruitment. Newly-developed cancer cases were determined from data in the government's National Cancer Registry and Death Certification System. For adipokienes study, a nested case-control study was conducted within the cohort. Baseline plasma samples of 40 incident gynecological cancer cases and 240 age-menopause-matched controls were assayed for adipokines levels.FindingsThere were 38 and 30 incident cases of UCC and OVC, respectively, diagnosed during a median 19.9 years of follow-up. Multivariate analysis showed that alcohol intake (HR = 16.00, 95% = 4.83-53.00), high triglyceride levels (HR = 2.58, 95% = 1.28-5.17), and years of endogenous estrogen exposure per 5-year increment (HR = 1.91, 95% = 1.08-3.38) were associated with increased UCC risk. High body mass index (BMI ≥ 27 kg/m(2), HR = 2.90, 95% = 1.30-6.46) was associated with increased OVC risk. Analysis further showed an independent effect of adipokines on UCC and OVC risk after adjustment of the risk covariates.ConclusionWe provided evidence that alcohol intake, high triglyceride levels and long endogenous estrogen exposure increase UCC risk, whereas obesity positively predicts OVC risk. Circulating adipokines may mediate the link of adiposity factors to gynecological cancer risk.

Dataset Information

A prospective study of circulating adipokine levels and risk of multiple myeloma.

Publications

A prospective study of circulating adipokine levels and risk of multiple myeloma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets