Faculty Bibliography

BACKGROUND:Cadmium (Cd) and lead (Pb) are hypothesised to be risk factors for non-Hodgkin's lymphoma (NHL), a group of haematological malignancies with a suspected environmental aetiology. Within the EnviroGenoMarkers study we utilised pre-diagnostic erythrocyte concentrations of Cd and Pb to determine whether exposure was associated with risk of B-cell NHL and multiple myeloma. METHODS:194 incident cases of B-cell NHL and 76 cases of multiple myeloma diagnosed between 1990 and 2006 were identified from two existing cohorts; EPIC-Italy and the Northern Sweden Health and Disease Study. Cases were matched to healthy controls by centre, age, gender and date of blood collection. Cd and Pb were measured in blood samples provided at recruitment using inductively coupled plasma-mass spectrometry. Logistic regression was applied to assess the association with risk. Analyses were stratified by cohort and gender and by subtype where possible. RESULTS:There was little evidence of an increased risk of B-cell NHL or multiple myeloma with exposure to Cd (B-cell NHL: OR 1.09 95%CI 0.61, 1.93, MM: OR 1.16 95% CI: 0.40, 3.40 ) or Pb (B-cell NHL: 0.93 95% CI 0.43, 2.02, multiple myeloma: OR 1.63 95%CI 0.45, 5.94) in the total population when comparing the highest to the lowest quartile of exposure. However, gender and cohort specific differences in results were observed. In females the risk of B-cell NHL was more than doubled in those with a body burden of Cd >1 µg/L (OR 2.20 95%CI; 1.04, 4.65). CONCLUSIONS:This nested case-control study does not support a consistent positive association between Cd or Pb and NHL, but there is some indication of a gender specific effect suggesting further research is warranted.

BACKGROUND:Data from a long-established hospital-based cancer registry were used to analyse the relationship between clinical and organisational factors and disease-specific survival among women with primary breast cancer. METHODS:2023 women with incident invasive breast cancer diagnosed from 1992 to 2005 were identified through the Hospital del Mar Cancer Registry (Barcelona, Spain). Patients were followed until December 2008. One-, 5- and 10-year disease-specific survival rates were estimated. Kaplan-Meier and Cox regression models were used to analyse death from breast cancer. RESULTS:At diagnosis 70.2% of tumours were in stages I-II. During follow-up 705 deaths occurred, 58.4% specifically due to breast cancer. Five- and 10-year breast cancer specific survival rates were 83.3% and 73.7%, respectively (stage I, 97.1% and 94.0%; stage II, 88.0% and 79.4%; stage III, 70.1% and 46.3%, and stage IV, 24.5% and 6.1%, respectively). The 5-year disease-specific survival rate increased from 73.5% in 1992-1995 to 86.4% in 2001-2005 (log rank, p<0.001). Multivariate analyses showed that prognosis was less favourable for women diagnosed between 1992 and 1995, for those whose route to diagnosis was not the screening programme, women aged ≥ 70 years, with stage IV tumours, with high grade lesions, and for women who received only palliative or symptomatic treatment. Adjusting for prognostic factors, surgeon's experience did not significantly appeared to affect survival of operated women. CONCLUSIONS:In this centre survival from breast cancer improved markedly from 1992 to 2005. Breast cancer prognosis was influenced by both clinical and organisational variables. The quantification of the role of such factors affords valuable knowledge to improve cancer care in settings similar to the study hospital.

BACKGROUND AND AIMS/OBJECTIVE:Knowledge on the aetiology of exocrine pancreatic cancer (EPC) is scant. The best established risk factor for EPC is tobacco smoking. Among other carcinogens, tobacco contains cadmium, a metal previously associated with an increased risk of EPC. This study evaluated the association between concentrations of trace elements in toenails and EPC risk. METHODS:The study included 118 EPC cases and 399 hospital controls from eastern Spain. Levels of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. OR and 95% CI, adjusted for potential confounders, were calculated using logistic regression. RESULTS:Significantly increased risks of EPC were observed among subjects whose concentrations of cadmium (OR 3.58, 95% CI 1.86 to 6.88; p(trend)=5×10(-6)), arsenic (OR 2.02, 95% CI 1.08 to 3.78; p(trend)=0.009) and lead (OR 6.26, 95% CI 2.71 to 14.47; p(trend)=3×10(-5)) were in the highest quartile. High concentrations of selenium (OR 0.05, 95% CI 0.02 to 0.15; p(trend)=8×10(-11)) and nickel (OR 0.27, 95% CI 0.12 to 0.59; p(trend)=2×10(-4)) were inversely associated with the risk of EPC. CONCLUSION/CONCLUSIONS:Novel associations are reported of lead, nickel and selenium toenail concentrations with pancreas cancer risk. Furthermore, the results confirm previous associations with cadmium and arsenic. These novel findings, if replicated in independent studies, would point to an important role of trace elements in pancreatic carcinogenesis.

We analyzed relationships of hepatic and pancreatic biomarkers with the cholestatic syndrome and tumor stage in exocrine pancreatic cancer (N = 183). Information on laboratory tests and on signs and symptoms was obtained from medical records and patient interviews. Bilirubin, aspartate aminotransferase (AST), γ-glutamyltransferase (GGT) and alkaline phosphatase were lower in tumor stage IV. The association was due to the relationship between cholestatic syndrome and earlier presentation of patients. There was no association between hepatic biomarkers and stage when adjusting by cholestatic syndrome. Relationships of hepatic and pancreatic biomarkers with pancreatic symptoms and tumor stage must be controlled in "-omics" and other studies using biomarkers.

Advances in laboratory techniques have led to a rapidly increasing use of biomarkers in epidemiological studies. Biomarkers of internal dose, early biological change, susceptibility, and clinical outcomes are used as proxies for investigating the interactions between external and/or endogenous agents and the body components or processes. The need for improved reporting of scientific research led to influential statements of recommendations such as STrengthening Reporting of Observational studies in Epidemiology (STROBE) statement. The STROBE initiative established in 2004 aimed to provide guidance on how to report observational research. Its guidelines provide a user-friendly checklist of 22 items to be reported in epidemiological studies, with items specific to the three main study designs: cohort studies, case-control studies and cross-sectional studies. The present STrengthening the Reporting of OBservational studies in Epidemiology - Molecular Epidemiology (STROBE-ME) initiative builds on the STROBE Statement implementing 9 existing items of STROBE and providing 17 additional items to the 22 items of STROBE checklist. The additions relate to the use of biomarkers in epidemiological studies, concerning collection, handling and storage of biological samples; laboratory methods, validity and reliability of biomarkers; specificities of study design; and ethical considerations. The STROBE-ME recommendations are intended to complement the STROBE recommendations.

BACKGROUND:Surveys of human exposure to environmental chemicals do not integrate the number of compounds detected per person and the concentration of each compound. This leaves untested relevant exposure scenarios, such as whether individuals with low concentrations of some compounds have high concentrations of the other compounds. OBJECTIVE:To analyze the number of persistent organic pollutants (POPs) detected at high concentrations. METHODS:Serum concentrations of 19 POPs were analyzed by gas chromatography with electron-capture detection in a representative sample of the general population of Catalonia, Spain (N=919). RESULTS:Over 58% of participants had concentrations in the top quartile of ≥1 of the eight most prevalent POPs, and 34% of ≥3 POPs. 83% of women 60 to 74 years old had concentrations of ≥3 POPs in the top quartile; 56% of women 60 to 74 years had p,p'-DDE, HCB and β-HCH all in their respective top quartiles, and 48% had concentrations of ≥6 POPs in the top quartile. Over 30% of subjects had concentrations in the top decile of 1 to 5 of the eight most prevalent POPs. Half of the population had levels of 1 to 5 POPs >500 ng/g. Less than 4% had all eight POPs in the lowest quartile. CONCLUSIONS:More than half of the study population had concentrations in the top quartile of ≥1 POPs. Significant subgroups of the population accumulate POP mixtures at high concentrations. POP concentrations appear low in most of the population only when each individual compound is looked at separately.

The aim was to analyze the effects of body mass index (BMI), low-dose exposure, mixtures of persistent organic pollutants (POPs), and lipid adjustment on the relationship between POP concentrations and diabetes and prediabetes in the general adult population of Catalonia (Spain). Serum concentrations of POPs were measured by gas chromatography with electron-capture detection in 886 participants in a health interview survey. The highest concentrations of all POPs analyzed were found in subjects who had diabetes. Levels were also higher in individuals with prediabetes than in subjects without the disorder. In models adjusted by age, sex and BMI, the prevalence of diabetes and prediabetes increased in a dose-dependent manner across quartiles of PCBs 118, 138, 153, and 180, and HCB. When models were further adjusted for lipids, the associations were slightly lower and statistically significant, the ORs for the upper quartile ranging from 2.0 to 2.8 (all p-values for linear trend <0.05). Concentrations of p,p'-DDT, p,p'-DDE and β-HCH were not associated with diabetes or prediabetes. Increasing concentrations of PCBs and HCB were positively associated with diabetes and prediabetes. Only part of the association was due to age and BMI. Findings support the hypothesis that exposure to POPs may be a diabetogenic factor in both obese and nonobese individuals.