In pancreatic ductal adenocarcinoma blood concentrations of some organochlorine compounds and coffee intake are independently associated with KRAS mutations

8 pages, 4 pages.-- PMID: 19797353 [PubMed].-- Printed version published Nov 2009.While KRAS activation is a fundamental initiating event in the aetiopathogenesis of pancreatic ductal adenocarcinoma (PDA), environmental factors influencing the occurrence and persistence of KRAS mutations remain largely unknown. The objective was to test the hypothesis that in PDA there are aetiopathogenic relationships among concentrations of some organochlorine compounds (OCs) and the mutational status of the KRAS oncogene, as well as among the latter and coffee intake. Incident cases of PDA were interviewed and had blood drawn at hospital admission (N = 103). OCs were measured by high-resolution gas chromatography with electron capture detection. Cases whose tumours harboured a KRAS mutation had higher concentrations of p,p′-dichlorodiphenyltrichloroethane (DDT), p,p′-dichlorodiphenyldichloroethene (DDE) and polychlorinated biphenyls (PCBs) 138, 153 and 180 than cases with wild-type KRAS, but differences were statistically significant only for p,p′-DDT and PCBs 138 and 153. The association between coffee intake and KRAS mutations remained significant (P-trend < 0.015) when most OCs where accounted for. When p,p′-DDT, PCB 153, coffee and alcohol intake were included in the same model, all were associated with KRAS (P = 0.042, 0.007, 0.016 and 0.025, respectively). p,p′-DDT, p,p′-DDE and PCB 138 were significantly associated with the two most prevalent KRAS mutations (Val and Asp). OCs and coffee may have independent roles in the aetiopathogenesis of PDA through modulation of KRAS activation, acquisition or persistence, plausibly through non-genotoxic or epigenetic mechanisms. Given that KRAS mutations are the most frequent abnormality of oncogenes in human cancers, and the lifelong accumulation of OCs in humans, refutation or replication of the findings is required before any implications are assessed.Government of Catalonia (2009 SGR 1350); ‘Red temática de investigación cooperativa de centros en Cáncer’ (C03/10); ‘Red temática de investigación cooperativa de centros en Epidemiología y salud pública’ (C03/09); CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III, Madrid, Government of Spain.Peer reviewe

Concordancia entre la información facilitada por el paciente y un familiar sobre antecedentes, patológicos, consumo de tabaco, de alcohol, de café, y dieta en el cáncer de páncreas exocrino y del sistema biliar extrahepático

ResumenObjetivoNingún estudio sobre mutaciones en el oncogén K-ras y los cánceres de páncreas exocrino y del sistema biliar ha analizado la fiabilidad de la información clínica y epidemiológica utilizada. En el contexto de un estudio prospectivo multicéntrico sobre dichas neoplasias se ha analizado la concordancia entre la información facilitada por el paciente y la facilitada por un familiar respecto a diversos factores asociados a aquéllas.MétodosSe cumplimentaron un total de 110 pares de entrevistas y el acuerdo se midió mediante los índices kappa simple (k) y ponderado (kp), el porcentaje de acuerdo simple, y los porcentajes de acuerdo para los valores positivos y negativos.ResultadosLa concordancia para los distintos antecedentes patológicos fue excelente (k entre 0,89 y 0,76), al igual que para el consumo habitual de tabaco (k=0,98). El acuerdo fue entre moderado y alto para el consumo habitual de café (k=0,68) y las frecuencias de consumo de grupos de alimentos (kp entre 0,66 y 0,38). Los familiares refirieron sistemáticamente un mayor consumo de bebidas alcohólicas que los pacientes (k entre 0,71 y 0,32).ConclusiónEn general, los familiares pueden tomarse como fuente de información alternativa en caso de incapacidad de los pacientes, aunque deben considerarse con cautela los datos referentes al consumo de alcohol.SummaryObjectiveNo study on mutations in the K-ras oncogene and cancer of the exocrine pancreas or cancer of the biliary system has analyzed the reliability of clinical and epidemiological information.MethodsAgreement between patient and surrogate on factors potentially related to both tumours was evaluated within a multicentre prospective study. Interviews were personally adminstered to both patient and surrogate (N=110 pairs). Agreement was examined viathe simple kappa index (k), the weighted kappa index (kw), the percentage of simple agreement, and the percentages of positive and negative agreement.ResultsAgreement for medical history was excellent (k between 0.89 and 0.76), as it was for tobacco consumption (k=0.98). Agreement was moderate for coffee consumption (k=0.68), frequencies of food groups (kw from 0.66 to 0.38), and consumption of alcoholic drinks (k from 0.66 to 0.32). Surrogates indicated a higher consumption of alcohol than patients.ConclusionSurrogates can be an alternative source of information when patients cannot be interviewed, but information on alcohol consumption should be treated with caution

Clinical validity of detecting K- mutations for the diagnosis of exocrine pancreatic cancer: a prospective study in a clinically-relevant spectrum of patients

International audienceThe diagnostic utility of detecting K- mutations for the diagnosis of exocrine pancreatic cancer (EPC) has not been properly studied, and few reports have analysed a clinically relevant spectrum of patients. The objective was to evaluate the clinical validity of detecting K- mutations in the diagnosis of EPC in a large sample of clinically relevant patients. We prospectively identified 374 patients in whom one of the following diagnoses was suspected at hospital admission: EPC, chronic pancreatitis, pancreatic cysts, and cancer of the extrahepatic biliary system. Mutations in the K- oncogene were analysed by PCR and artificial RFLP in 212 patients. The sensitivity and specificity of the K- mutational status for the diagnosis of EPC were 77.7% (95% CI: 69.2-84.8) and 78.0% (68.1-86.0), respectively. The diagnostic accuracy was hardly modified by sex and age. In patients with either mutated K- or CEA > 5 ng/ml, the sensitivity and specificity were 81.0% (72.9-87.6) and 62.6% (72.9-87.6), respectively. In patients with mutated K- and CEA > 5 ng/ml the sensitivity was markedly reduced. In comparisons with a variety of non-EPC patient groups sensitivity and specificity were both always greater than 75%. In this clinically relevant sample of patients the sensitivity and specificity of K- mutations were not sufficiently high for independent diagnostic use. However, it seems premature to rule out the utility of K- analysis in conjunction with other genetic and 'omics' technologies