Pre-diagnostic serum concentrations of organochlorines and risk of acute myeloid leukemia: A nested case-control study in the Norwegian Janus Serum Bank Cohort

Background: Epidemiologic studies suggest an increased risk of leukemia among individuals occupationally exposed to some organochlorine (OC) compounds. Associations between serum OC pesticide and polychlorinated biphenyl (PCB) levels and risk of acute myeloid leukemia (AML), the most common subtype of acute leukemia in adult populations, have not been evaluated prospectively in the general population. Objective: We evaluated the risk of AML in relation to pre-diagnostic serum levels of OC pesticides and PCBs in a case-control study nested within the Janus Serum Bank Cohort. Methods: Janus is a large population-based cohort containing biologic samples collected beginning in the early 1970s from ~318,000 individuals in Norway. Serum levels of 11 OC pesticides or their metabolites and 34 PCB congeners were measured in 56 AML cases and 288 controls. Conditional logistic regression was conducted to evaluate associations between lipid-adjusted serum OC levels and risk of AML. Results: Higher serum levels of total chlordane/heptachlor metabolites were associated with AML risk (3rd vs. 1st tertile odds ratio (OR) = 2.26, 95% confidence interval (CI) = 0.91–5.63; ptrend = 0.11). Significant exposure-response associations were observed for levels of heptachlor epoxide (3rd vs. 1st tertile OR = 2.85, 95% CI = 1.05–7.73; ptrend = 0.02) and dieldrin (3rd vs. 1st tertile OR = 2.71, 95% CI = 1.07–6.83; ptrend = 0.03). No significant exposure-response associations with AML risk were observed for total DDT or individual isomers and derivatives. Higher serum levels of p,p′-DDT showed a non-significant increase in risk, but the exposure-response became attenuated when co-adjusting for heptachlor epoxide or dieldrin levels. Serum PCB levels were not significantly associated with AML risk. Conclusions: Our data suggest that higher serum levels of dieldrin and metabolites derived from chlordane/heptachlor are associated with risk of AML in the general Norwegian population, based on samples collected on average ~17 years before diagnosis. Further research in populations with historically high or recent exposure to DDT is warranted to assess the association with AML risk with body burden of specific DDT isomers and derivatives

Volume Tracking: A new method for quantitative assessment and visualization of intracardiac blood flow from three-dimensional, time-resolved, three-component magnetic resonance velocity mapping

<p>Abstract</p> <p>Background</p> <p>Functional and morphological changes of the heart influence blood flow patterns. Therefore, flow patterns may carry diagnostic and prognostic information. Three-dimensional, time-resolved, three-directional phase contrast cardiovascular magnetic resonance (4D PC-CMR) can image flow patterns with unique detail, and using new flow visualization methods may lead to new insights. The aim of this study is to present and validate a novel visualization method with a quantitative potential for blood flow from 4D PC-CMR, called Volume Tracking, and investigate if Volume Tracking complements particle tracing, the most common visualization method used today.</p> <p>Methods</p> <p>Eight healthy volunteers and one patient with a large apical left ventricular aneurysm underwent 4D PC-CMR flow imaging of the whole heart. Volume Tracking and particle tracing visualizations were compared visually side-by-side in a visualization software package. To validate Volume Tracking, the number of particle traces that agreed with the Volume Tracking visualizations was counted and expressed as a percentage of total released particles in mid-diastole and end-diastole respectively. Two independent observers described blood flow patterns in the left ventricle using Volume Tracking visualizations.</p> <p>Results</p> <p>Volume Tracking was feasible in all eight healthy volunteers and in the patient. Visually, Volume Tracking and particle tracing are complementary methods, showing different aspects of the flow. When validated against particle tracing, on average 90.5% and 87.8% of the particles agreed with the Volume Tracking surface in mid-diastole and end-diastole respectively. Inflow patterns in the left ventricle varied between the subjects, with excellent agreement between observers. The left ventricular inflow pattern in the patient differed from the healthy subjects.</p> <p>Conclusion</p> <p>Volume Tracking is a new visualization method for blood flow measured by 4D PC-CMR. Volume Tracking complements and provides incremental information compared to particle tracing that may lead to a better understanding of blood flow and may improve diagnosis and prognosis of cardiovascular diseases.</p

Timing of HPV16-E6 antibody seroconversion before OPSCC : findings from the HPVC3 consortium

Background: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. Patients and methods: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). Results: HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time 30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and Conclusions: The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.Peer reviewe

Prediagnostic blood levels of organochlorines and risk of non‐Hodgkin lymphoma in three prospective cohorts in China and Singapore

Specific organochlorines (OCs) have been associated with non-Hodgkin lymphoma (NHL) with varying degrees of evidence. These associations have not been evaluated in Asia, where the high exposure and historical environmental contamination of certain OC pesticides (e.g., dichlorodiphenyltrichloroethane [DDT], hexachlorocyclohexane [HCH]) are different from Western populations. We evaluated NHL risk and prediagnostic blood levels of OC pesticides/metabolites and polychlorinated biphenyl congeners in a case–control study of 167 NHL cases and 167 controls nested within three prospective cohorts in Shanghai and Singapore. Conditional logistic regression was used to analyze lipid-adjusted OC levels and NHL risk. Median levels of p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE), the primary DDT metabolite, and β-HCH were up to 12 and 65 times higher, respectively, in samples from the Asian cohorts compared to several cohorts in the United States and Norway. An increased risk of NHL was observed among those with higher β-HCH levels both overall (3rd vs. 1st tertile OR = 1.8, 95%CI = 1.0–3.2; ptrend = 0.049) and after excluding cases diagnosed within 2 years of blood collection (3rd vs. 1st tertile OR = 2.0, 95%CI = 1.1–3.9; ptrend = 0.03), and the association was highly consistent across the three cohorts. No significant associations were observed for other OCs, including p,p′-DDE. Our findings provide support for an association between β-HCH blood levels and NHL risk. This is a concern because substantial quantities of persistent, toxic residues of HCH are present in the environment worldwide. Although there is some evidence that DDT is associated with NHL, our findings for p,p′-DDE do not support an association