No abstract

Hereditary factors are thought to play a role in at least one third of patients with colorectal cancer (CRC) but only a limited proportion of these have mutations in known high‐penetrant genes. In a relatively large part of patients with a few or multiple colorectal polyps the underlying genetic cause of the disease is still unknown. Using exome sequencing in combination with linkage analyses together with detection of copy‐number variations (CNV), we have identified a duplication in the regulatory region of the GREM1 gene in a family with an attenuated/atypical polyposis syndrome. In addition, 107 patients with colorectal cancer and/or polyposis were analyzed for mutations in the candidate genes identified. We also performed screening of the exonuclease domain of the POLE gene in a subset of these patients. The duplication of 16 kb in the regulatory region of GREM1 was found to be disease‐causing in the family. Functional analyses revealed a higher expression of the GREM1 gene in colorectal tissue in duplication carriers. Screening of the exonuclease domain of POLE in additional CRC patients identified a probable causative novel variant c.1274A>G, p.Lys425Arg. In conclusion a high penetrant duplication in the regulatory region of GREM1, predisposing to CRC, was identified in a family with attenuated/atypical polyposis. A POLE variant was identified in a patient with early onset CRC and a microsatellite stable (MSS) tumor. Mutations leading to increased expression of genes can constitute disease‐causing mutations in hereditary CRC syndromes. © 2015 The Authors. Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc.

The overall aim of this study was to investigate whether time pressure and verbal provocation has any effect on physiological and psychological reactions during work with a computer mouse. It was hypothesised that physiological reactions other than muscle activity (i.e. wrist movements, forces applied to the computer mouse) would not be affected when working under stressful conditions. Fifteen subjects (8 men and 7 women) participated, performing a standardised text-editing task under stress and control conditions. Blood pressure, heart rate, heart rate variability, electromyography, a force-sensing computer mouse and electrogoniometry were used to assess the physiological reactions of the subjects. Mood ratings and ratings of perceived exertion were used to assess their psychological reactions. The time pressure and verbal provocation (stress situation) resulted in increased physiological and psychological reactions compared with the two control situations. Heart rate, blood pressure and muscle activity in the first dorsal interosseus, right extensor digitorum and right trapezius muscles were greater in the stress situation. The peak forces applied to the button of the computer mouse and wrist movements were also affected by condition. Whether the increases in the physiological reactions were due to stress or increased speed/productivity during the stress situation is discussed. In conclusion, work with a computer mouse under time pressure and verbal provocation (stress conditions) led to increased physiological and psychological reactions compared to control conditions.

Treatment with EPO at a dose of 10,000 U thrice weekly can rapidly and safely increase B-Hb levels in a high proportion of patients with advanced gastrointestinal cancers. QoL is influenced by the B-Hb increase, but also by the course of the underlying malignancy. It is therefore difficult to define clearly the clinical relevance of the B-Hb increase as such.

We investigated the value of the GC combination as a treatment for late stage breast cancer patients. Tumour progression was delayed and the treatment was well tolerated. We believe that the GC therapy can achieve meaningful palliation.