Influence of KRAS mutations, persistent organic pollutants, and trace elements on survival from pancreatic ductal adenocarcinoma

摘要: ABSTRACT Introduction Reasons why pancreatic ductal adenocarcinoma (PDAC) continues to have poor survival are only partly known. No previous studies analyzed the combined influence of KRAS mutations, persistent organic pollutants (POPs), and trace elements upon in PDAC or any other human cancer. Objective To analyze individual POPs, from PDAC. Methods Incident cases (n = 185) were prospectively identified five hospitals Eastern Spain 1992-1995 interviewed face-to-face during hospital admission. mutational status was determined tumour tissue through polymerase chain reaction artificial restriction fragment length polymorphism. Blood toenail samples obtained before treatment. Serum concentrations POPs by high-resolution gas chromatography with electron-capture detection. Concentrations 12 inductively coupled plasma mass spectrometry. Multivariable Cox proportional hazards regression used assess prognostic associations. Results Patients a mutated tumor had 70% higher risk early death than patients wild-type (hazard ratio [HR] 1.7, p 0.026), adjusting for age, sex, stage. modestly not statistically significantly associated when further treatment intention. The beneficial effects remained unaltered taken into account, did appear be less effective subgroup tumor. materially survival: adjusted HR highest POP tertiles near unity all POPs. When considering joint effect on KRAS, tumors modest nonsignificant HRs (most around 1.3 1.4). Higher lead, cadmium, arsenic, vanadium, aluminium better survival. status, simultaneously considered along treatment, latter related Conclusions In this study based molecular, clinical, environmental epidemiology, adversely considered; independently lack adverse metals measured at time diagnosis provide scientific clinical reassurance such exposures weak association mutations contributes scant knowledge implications genetic alteration highly frequent