Suicides among Danish cancer patients 1971–1999

Compared to the general population, the suicide risk among Danish cancer patients diagnosed in 1971–1986 was increased by 50% for men and 30% for women. We updated the earlier study to evaluate both long-term and recent trends in the suicide risk. Cancer patients with a first cancer diagnosed between 1971 and 1999 in Denmark were followed-up for completed suicide through 1999. Excluding nonmelanoma skin cancer, 564 508 cancer patients were included and 1241 suicides observed. Both the standardised mortality ratio (SMR) of suicide relative to the general population and the suicide rates were analysed with Poisson regression methods. The overall SMR was increased to 1.7 (95% CI. 1.6–1.9) for men and 1.4 (95% CI: 1.3–1.5) for women. Following the cancer diagnosis, the suicide risk was highest in the first 3 months for men and between months 3 and 12 for women. The risk was higher for nonlocalised cancer and for cancers with perceived poor prognosis. Breast cancer patients had a higher risk than other cancer patients with similar good prognosis. The suicide rates among cancer patients decreased with calendar time, but less so than the rates in the general population. The suicide risk among cancer patients has not decreased as much as in the Danish population and reasons for this should be explored. Breast cancer might be believed by patients to be more life threatening than it is. Assessment and treatment of depression could improve the quality of life for cancer patients who suffer from unrecognised depressions and in turn reduce the risk of suicide in cancer patients

Sequence-Specific Solvent Accessibilities of Protein Residues in Unfolded Protein Ensembles

Protein stability cannot be understood without the correct description of the unfolded state. We present here an efficient method for accurate calculation of atomic solvent exposures for denatured protein ensembles. The method used to generate the ensembles has been shown to reproduce diverse biophysical experimental data corresponding to natively and chemically unfolded proteins. Using a data set of 19 nonhomologous proteins containing from 98 to 579 residues, we report average accessibilities for all residue types. These averaged accessibilities are considerably lower than those previously reported for tripeptides and close to the lower limit reported by Creamer and co-workers. Of importance, we observe remarkable sequence dependence for the exposure to solvent of all residue types, which indicates that average residue solvent exposures can be inappropriate to interpret mutational studies. In addition, we observe smaller influences of both protein size and protein amino acid composition in the averaged residue solvent exposures for individual proteins. Calculating residue-specific solvent accessibilities within the context of real sequences is thus necessary and feasible. The approach presented here may allow a more precise parameterization of protein energetics as a function of polar- and apolar-area burial and opens new ways to investigate the energetics of the unfolded state of proteins

A Self-Consistent Description of the Conformational Behavior of Chemically Denatured Proteins from NMR and Small Angle Scattering

Characterization of the conformational properties of unfolded proteins is essential for understanding the mechanisms of protein folding and misfolding. This information is also fundamental to determining the relationship between flexibility and function in the highly diverse families of intrinsically disordered proteins. Here we present a self-consistent model of conformational sampling of chemically denatured proteins in agreement with experimental data reporting on long-range distance distributions in unfolded proteins using small-angle x-ray scattering and nuclear magnetic resonance pulse-field gradient-based measurements. We find that standard statistical coil models, selected from folded protein databases with secondary structural elements removed, need to be refined to correct backbone dihedral angle sampling of denatured proteins, although they appear to be appropriate for intrinsically disordered proteins. For denatured proteins, pervasive increases in the sampling of more-extended regions of Ramachandran space {50°< ψ < 180°} throughout the peptide chain are found to be consistent with all experimental data. These observations are in agreement with previous conclusions derived from short-range nuclear magnetic resonance data from residual dipolar couplings, leading the way to a self-consistent description of denatured chains that is in agreement with short- and long-range data measured using both spectroscopic and scattering techniques