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Abstract Follow-up of low-risk monoclonal gammopathy of undetermined significance (MGUS) is debated as multiple myeloma (MM) progression risk is low. Worse MM outcome was reported for patients followed for low-risk MGUS, possibly due to less optimal follow-up. However, it is unknown whether progressing low-risk MGUS is associated with aggressive tumor behavior. Understanding these patterns is crucial for MGUS management. Here, we investigated whether progression from low-risk MGUS is associated with worse MM outcome in patients who had no MGUS follow-up before myeloma diagnosis. We retrospectively determined the MGUS status in repeated pre-diagnostic blood samples prospectively collected from 42 myeloma patients in median 11.6 years (first sample) and 3.3 years (repeated sample) before myeloma diagnosis. At first pre-diagnostic blood draw, 12 had low-risk (defined by an immunoglobulin [Ig] G monoclonal [M] spike

Abstract Background Chronic kidney disease has emerged as a strong cardiovascular risk factor, and in many current guidelines, it is already considered as a coronary heart disease (CHD) equivalent. Routinely, creatinine has been used as the main marker of renal function, but recently, cystatin C emerged as a more promising marker. The aim of this study was to assess the comparative cardiovascular and mortality risk of chronic kidney disease (CKD) using cystatin C-based and creatinine-based equations of the estimated glomerular filtration rate (eGFR) in participants of population-based and disease cohorts. Methods The present study has been conducted within the BiomarCaRE project, with harmonized data from 20 population-based cohorts (n = 76,954) from 6 European countries and 3 cardiovascular disease (CVD) cohorts (n = 4982) from Germany. Cox proportional hazards models were used to assess hazard ratios (HRs) for the various CKD definitions with adverse outcomes and mortality after adjustment for the Systematic COronary Risk Evaluation (SCORE) variables and study center. Main outcome measures were cardiovascular diseases, cardiovascular death, and all-cause mortality. Results The overall prevalence of CKD stage 3–5 by creatinine- and cystatin C-based eGFR, respectively, was 3.3% and 7.4% in the population-based cohorts and 13.9% and 14.4% in the disease cohorts. CKD was an important independent risk factor for subsequent CVD events and mortality. For example, in the population-based cohorts, the HR for CVD mortality was 1.72 (95% CI 1.53 to 1.92) with creatinine-based CKD and it was 2.14 (95% CI 1.90 to 2.40) based on cystatin-based CKD compared to participants without CKD. In general, the HRs were higher for cystatin C-based CKD compared to creatinine-based CKD, for all three outcomes and risk increased clearly below the conventional threshold for CKD, also in older adults. Net reclassification indices were larger for a cystatin-C based CKD definition. Differences in HRs (between the two CKD measures) in the disease cohorts were less pronounced than in the population-based cohorts. Conclusion CKD is an important risk factor for subsequent CVD events and total mortality. However, point estimates of creatinine- and cystatin C-based CKD differed considerably between low- and high-risk populations. Especially in low-risk settings, the use of cystatin C-based CKD may result in more accurate risk estimates and have better prognostic value.

Abstract Background Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex. Methods In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P

Abstract Background Vitamin D has been implicated as being involved in the aetio-pathogenesis of several autoimmune diseases including rheumatoid arthritis (RA). Previous studies present contradictory results. Vitamin D binding protein (DBP), the major transport protein, is also involved in various inflammatory processes. The aim of this study was to investigate the relationship between circulating levels of 25-hydroxyvitamin D [25(OH) D], DBP and polymorphisms in group-specific component (GC) in pre-symptomatic individuals and matched controls within prospective cohorts of the Northern Sweden. Methods Blood samples donated to the Medical Biobank prior to the onset of symptoms of RA (n = 515, mean [SD] time before the onset of symptoms 6.2 [9.3] years) and from matched (2:1) population-based controls (n = 267) were used. Plasma 25(OH) vitamin D levels were analyzed using liquid chromatography tandem-mass spectrometry and DBP levels were analyzed using enzyme-linked immunosorbent assay. GC polymorphisms (rs4588 and rs7041) were analyzed with TaqMan assays (Applied Biosystems). Results Levels of 25(OH) D or DBP were not statistically different between pre-symptomatic individuals and controls in a crude, or a multiple-adjusted logistic regression model. However, an increased risk for future RA was found in females of DBP (OR 1.014 [95%CI 1.001–1.028]) per 10 mg/L adjusted for carriage of the minor allele of rs4588, in a multiple-adjusted model (p