BACKGROUND Biomarkers and metabolites related to B vitamin function and one-carbon metabolism have been studied as predictors of chronic diseases in studies based on samples stored in biobanks. For most biomarkers, stability data are lacking or fragmentary. METHODS Degradation and accumulation kinetics of 32 biomarkers were determined at 23 °C in serum and plasma (EDTA, heparin, and citrate) collected from 16 individuals and stored for up to 8 days. In frozen serum (−25 °C), stability was studied cross-sectionally in 650 archival samples stored for up to 29 years. Concentration vs time curves were fitted to monoexponential, biexponential, linear, and nonlinear models. RESULTS For many biomarkers, stability was highest in EDTA plasma. Storage effects were similar at room temperature and at −25 °C; notable exceptions were methionine, which could be recovered as methionine sulfoxide, and cystathionine, which decreased in frozen samples. Cobalamin, betaine, dimethylglycine, sarcosine, total homocysteine, total cysteine, tryptophan, asymetric and symmetric dimethyl argenine, creatinine, and methylmalonic acid were essentially stable under all conditions. Most B vitamins (folate and vitamins B2 and B6) were unstable; choline increased markedly, and some amino acids also increased, particularly in serum. The kynurenines showed variable stability. For many biomarkers, degradation (folate and flavin mononucleotide) or accumulation (pyridoxal, riboflavin, choline, amino acids) kinetics at room temperature were non–first order. CONCLUSIONS Data on stability and deterioration kinetics for individual biomarkers are required to optimize procedures for handling serum and plasma, and for addressing preanalytical bias in epidemiological and clinical studies.

Cytokines and cytokine-related markers appear to be upregulated rather late in RA pathogenesis. In contrast, IgM rheumatoid factor and IgG anti-cyclic citrullinated peptide autoantibodies may precede the diagnosis of RA by up to two decades.

BackgroundExperimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting.ObjectiveTo examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer.Design, setting, and participantsAnalysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group.Outcome measurements and statistical analysisOdds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration.Results and limitationsMen in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR = 0.77, 95% confidence interval [CI] 0.69–0.86; p < 0.001) compared with men with higher concentrations (2nd–10th tenths of the distribution). Heterogeneity was present by tumour grade (phet = 0.01), with a lower risk of low-grade disease (OR = 0.76, 95% CI 0.67–0.88) and a nonsignificantly higher risk of high-grade disease (OR = 1.56, 95% CI 0.95–2.57). There was no evidence of heterogeneity by tumour stage. The observational design is a limitation.ConclusionsMen with low circulating free testosterone may have a lower risk of overall prostate cancer; this may be due to a direct biological effect, or detection bias. Further research is needed to explore the apparent differential association by tumour grade.Patient summaryIn this study, we looked at circulating testosterone levels and risk of developing prostate cancer, finding that men with low testosterone had a lower risk of prostate cancer.

Circulating microRNAs in human serum have increasingly been recognized as stable markers for cancer detection. However, there is still a lack of miRNome wide studies over a long period of time with respect to pathogenic processes. We obtained serum samples from the janus serum bank collected prior and after diagnosis of lung cancer. We analyzed the abundance of 904 miRNAs in serum from eight cancer patients at three time points and from six healthy control individuals. Based on the identified miRNA signatures, hierarchical clustering and a self-organizing map identified three major clusters including one cluster containing most of the of the pre-diagnostic samples, a second cluster with mainly post-diagnostic samples, and a third cluster with mainly control samples. Correlation analyses showed that although the profiles were generally stable over several years, most obvious changes of the miRNA pattern seem to occur at a time close to diagnosis. Our findings support the idea that a developing lung cancer might be detectable years prior to diagnosis through a specific miRNA signature and that this signature changes during tumor development.

Past infection with HPV16 increases the risk of invasive cervical squamous cell carcinoma, most clearly seen in populations with a low prevalence of sexually transmitted diseases.

(2007) Nordic biological specimen banks as basis for studies of cancer causes and control -more than 2 million sample donors, 25 million person years and 100 000 prospective cancers, Acta Oncologica, 46:3,

Cutaneous human papillomaviruses (HPVs) have been associated with squamous cell carcinoma (SCC) in case-control studies, but there are limited data from prospective studies assessing whether virus exposure predicts risk of future cancer development. Two major biobanks, the Southern Sweden Microbiology Biobank (1971-2003) and the Janus Biobank (1973-2003) in Norway, containing samples from 850,000 donors, were searched for incident skin cancer for up to 30 years using registry linkages. Altogether, 2,623 donors with samples taken before diagnosis of SCC or basal cell carcinoma (BCC) of the skin were identified. Prediagnostic samples and samples from 2,623 matched controls were tested for antibodies against 33 types of HPV. Baseline seropositivity to HPV types in genus β species 2 was associated with SCC risk (odds ratio = 1.3, 95% confidence interval: 1.1, 1.7); this was also the case for samples taken more than 18 years before diagnosis (odds ratio = 1.8, 95% confidence interval: 1.1, 2.8). Type-specific persistent seropositivity entailed elevated point estimates for SCC risk for 29 HPV types and decreased point estimates for only 3 types. After multiple hypothesis adjustment, HPV 76 was significantly associated with SCC risk and HPV 9 with BCC risk. In summary, seropositivity for certain HPV types was associated with an increased risk for future development of SCC and BCC.

The findings showed that long-term storage can introduce a considerable bias for vulnerable components.