Tomàs López

Pancreatic cancer risk and levels of trace elements

Background and Aims 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; ptrend=5×10−6), arsenic (OR 2.02, 95% CI 1.08 to 3.78; ptrend=0.009) and lead (OR 6.26, 95% CI 2.71 to 14.47; ptrend=3×10−5) were in the highest quartile. High concentrations of selenium (OR 0.05, 95% CI 0.02 to 0.15; ptrend=8×10−11) and nickel (OR 0.27, 95% CI 0.12 to 0.59; ptrend=2×10−4) were inversely associated with the risk of EPC. Conclusion 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.

Correcting serum concentrations of organochlorine compounds by lipids: alternatives to the organochlorine/total lipids ratio.

INTRODUCTION When studying the effects of organochlorine compounds (OCs) on human health it is common to correct serum concentrations of OC by total lipids (TL). However, the relationship between serum OCs and serum TL is far from established in many diseases, including several cancers. Our aim was to analyze the relationship between serum OC and TL in patients with pancreatic ductal adenocarcinoma (PDA), and to explore several alternatives to perform the OC lipid correction. METHODS Incident cases of PDA were interviewed and had blood drawn soon around hospital admission (n=144). Serum concentrations of OCs were analysed by high-resolution gas chromatography with electron-capture detection. RESULTS Most patients with high TL had moderate or low concentrations of OCs. By contrast, the variability of OC values among patients with normal TL was large. Correlations were of a similar magnitude between OC and TL and between OC and total cholesterol; while these correlations were weak (all Spearmans rho<0.3 and R(2)<0.11), no OC were significantly correlated with triglycerides. Although all alternatives to the OC/TL linear ratio were statistically significant for at least one OC, their R(2) was always below 10%. CONCLUSIONS In patients with severe diseases as PDA, linear correction of OC by TL as commonly performed in epidemiologic studies may be inappropriate. Results contribute to the scant literature on the rationale to correct serum concentrations of OC by lipids. They suggest that it is unwarranted to routinely correct OC by TL, offer ways to assess such need, and present alternatives as no TL correction, correction by total cholesterol only or use of different statistical models.

Food and nutrient intakes and K-ras mutations in exocrine pancreatic cancer

Background: No studies have investigated the relation between K-ras mutations and dietary factors in exocrine pancreatic cancer (EPC), and fewer than 10 studies have done so in other neoplasms. Patients and Methods: Incident cases of EPC were prospectively identified, and interviewed face-to-face during hospital admission. Food and nutrient intakes were measured with a food frequency questionnaire. Logistic regression was used to compare EPC cases (n = 107) with and without K-ras mutations (case-case study). Results: K-ras mutations were more common among daily consumers of milk and other dairy products than among non-daily consumers: the odds ratio adjusted by total energy, age, sex, smoking, alcohol and coffee consumption (ORa) was 5.1 (95% CI 1.1 to 24.5, p = 0.040). For all dairy products, including butter, the ORa for the medium and upper tertiles of intake were 5.4 and 11.6, respectively (p for trend = 0.023). The ORa for regular coffee drinkers further adjusted by dairy consumption was 4.7 (95% CI 1.1 to 20.7, p = 0.043). K-ras mutated cases reported a lower intake of vitamin E (ORa = 0.2, p for trend = 0.036), polyunsaturated fats and omega 3 fatty acids (ORa = 0.2; p for trend <0.03). Conclusions: Results support the hypothesis that in EPC exposure to specific dietary components or contaminants may influence the occurrence or persistence of K-ras mutations.

Trends in citations to books on epidemiological and statistical methods in the biomedical literature.

Background There are no analyses of citations to books on epidemiological and statistical methods in the biomedical literature. Such analyses may shed light on how concepts and methods changed while biomedical research evolved. Our aim was to analyze the number and time trends of citations received from biomedical articles by books on epidemiological and statistical methods, and related disciplines. Methods and Findings The data source was the Web of Science. The study books were published between 1957 and 2010. The first year of publication of the citing articles was 1945. We identified 125 books that received at least 25 citations. Books first published in 1980–1989 had the highest total and median number of citations per year. Nine of the 10 most cited texts focused on statistical methods. Hosmer & Lemeshows Applied logistic regression received the highest number of citations and highest average annual rate. It was followed by books by Fleiss, Armitage, et al., Rothman, et al., and Kalbfleisch and Prentice. Fifth in citations per year was Sackett, et al., Evidence-based medicine. The rise of multivariate methods, clinical epidemiology, or nutritional epidemiology was reflected in the citation trends. Educational textbooks, practice-oriented books, books on epidemiological substantive knowledge, and on theory and health policies were much less cited. None of the 25 top-cited books had the theoretical or sociopolitical scope of works by Cochrane, McKeown, Rose, or Morris. Conclusions Books were mainly cited to reference methods. Books first published in the 1980s continue to be most influential. Older books on theory and policies were rooted in societal and general medical concerns, while the most modern books are almost purely on methods.

Influence of tumor stage, symptoms, and time of blood draw on serum concentrations of organochlorine compounds in exocrine pancreatic cancer

BackgroundKnowledge is scant on the relationships between pathophysiologic processes common during cancer progression and changes in blood concentrations of organochlorine compounds (OCs).ObjectiveTo analyze the influence of tumor stage, cancer symptoms, and time of blood extraction on serum concentrations of OCs in exocrine pancreatic cancer (EPC).MethodsSubjects were 144 incident cases of EPC prospectively recruited in eastern Spain. Blood was drawn and face-to-face interviews with patients were conducted during hospital admission. Information on signs and symptoms was obtained from medical records and patient interviews. OCs were analyzed by high-resolution gas chromatography with electron-capture detection. General linear models were applied to analyze log-transformed OCs corrected for total lipids.ResultsLower concentrations of six of the seven OCs analyzed (p,p′-DDE, three polychlorinated biphenyls, hexachlorobenzene, and β-hexachlorocyclohexane) were observed in patients with cholestatic syndrome (jaundice, hypocholia, and choluria). The constitutional syndrome increased only p,p′-DDT. The lowering effect of the cholestatic syndrome was stronger than the increasing effect of the constitutional syndrome (fatigue, anorexia, and weight loss), except for p,p′-DDT. When symptoms were considered, stage had only weakly inverse relationships with OC levels. The effects of symptoms on p,p′-DDE, p,p′-DDT, and the three PCBs remained significant after adjusting by the interval from blood extraction to first symptom of EPC, and even when further adjusting by stage.ConclusionsRestriction or adjustment by stage and timing of blood draw may be insufficient to prevent biases associated with cancer progression. Symptoms may enable investigators to assess disease-induced changes in lipophilic exposure biomarkers.

Number of Persistent Organic Pollutants Detected at High Concentrations in Blood Samples of the United States Population.

Human exposure to environmental chemicals as persistent organic pollutants (POPs) is usually assessed considering each pollutant individually, with little attention to concentrations of mixtures in individuals or social groups. Yet, it may be relatively common for humans to have low and high concentrations of numerous POPs. The study objectives were to analyze the number of POPs detected per person at high concentrations in the U.S. population, and the associations between such type of indicators and socioeconomic factors as gender, race / ethnicity, education, and poverty level. From 91 POPs analyzed in serum samples of 4,739 individuals in three subsamples of the National Health and Nutrition Examination Survey (NHANES) 2003–2004 (the last period with valid updated individual data for the compounds considered in the present study), we computed the number of POPs whose serum concentrations were above selected cutoff points. POPs included were 13 organochlorine compounds (OCs), 10 polybrominated diphenyl ethers (PBDEs), the polybrominated biphenyl (PBB) 153, 38 polychlorinated biphenyls (PCBs), 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/Fs), and 12 perfluorinated compounds (PFCs). Over 13% of participants had ≥10 of the 37 most detected POPs each at a concentration in the top decile (P90). Over 30% of subjects with total toxic equivalency (TEQ) ≥P75, had ≥10 of 24 POPs not included in TEQ calculations at concentrations ≥P90. Compared to non-Hispanic whites, the adjusted odds ratio of having ≥10 of the 37 POPs at P90 was 9.2 for non-Hispanic blacks and 0.18 for Mexican Americans. Poverty, body mass index, age, and gender were also independently associated with having ≥10 POPs in the top decile. More than one tenth of the US population may have ≥10 POPs each at concentrations in the top decile. Such pattern is nine times more frequent in Non-Hispanic blacks and four times less frequent in Mexican Americans than in non-Hispanic whites.

Lifetime history of alcohol consumption and K-ras mutations in pancreatic ductal adenocarcinoma.

In pancreatic ductal adenocarcinoma (PDA), evidence on the etiopathogenic role of alcohol consumption in the occurrence of K‐ras mutations is scant, and the role of alcohol in pancreatic carcinogenesis is not well established. We analyzed the relation between lifetime consumption of alcohol and mutations in codon 12 of the K‐ras oncogene in patients with PDA.

Evaluation of the importance of germinative cycles for destruction of bacillus cereus spores in miniature cheeses

Our objective was to determine the effect of high pressure on inactivation of spores of Bacillus cereus ATCC 9139 inoculated into cheese made of raw cows milk. Inoculated miniature cheeses were manufactured under controlled bacteriological conditions, vacuum packed and kept at 8 °C for 15 days after pressure treatment. Cheeses were submitted to pressures of 300, 400 or 500 MPa at 30 °C, during 15 min. Some of them were treated with a germination cycle of 60 MPa at 30 °C for 210 min. Lethality was calculated comparing surviving sample counts to control ones. Adding the germinative cycle resulted in higher efficiency, and when applied with 500 MPa, lethality reached 2.0 log cfu/mL. We saw that with both cycles initial counts of spores diminish, but all of them were not inactivated. However, considering that in raw milk mesophilic spore counts are 2.6-2.9 log cfu/mL, this treatment may be useful.

How useful is it clinically to analyse the K-ras mutational status for the diagnosis of exocrine pancreatic cancer? A systematic review and meta-analysis

Eur J Clin Invest 2011; 41 (7): 793–805

Contamination from endocrine disrupters of the general population at low and high concentrations.

Analyses of the concentrations of a given environmental compound usually show that most citizens have much lower concentrations than a certain minority, whose members have high body concentrations. Surveys of human exposure to chemicals do not usually integrate the number of chemical compounds detected per person and the concentration of each compound. This leaves untested relevant exposure situations, for example, whether individuals with low concentrations of some compounds have high concentrations of the other compounds. On scientific grounds, it is puzzling that this possibility, arithmetically and conceptually rather simple, has seldom if ever been tested in studies based on a representative sample of the general population. A study based on a representative sample of the general population of Catalonia (Spain) (Porta, Pumarega, & Gasull, 2012), which integrated the number of compounds detected per person and the concentration of each compound, found that more than half of the population had concentrations in the top quartile of 1 or more of the 19 persistent toxic substances (PTS) (pesticides and polychlorinated biphenyls) analyzed. Significant subgroups of the population accumulated PTS mixtures at high concentrations. For instance, 48% of women 60-74 years had concentrations of 6 or more PTS in the top quartile; half of the entire population had levels of 1-5 PTS above 500 ng/g, and less than 4% of citizens had all PTS in the lowest quartile. Thus, PTS concentrations appear low in most of the population only when each individual compound is looked at separately. It is not accurate to state that most of the population has low concentrations of PTS. The assessment of mixture effects must address the fact that most individuals are contaminated by PTS mixtures made of compounds at both low and high concentrations.