Signatures of mutational processes in human cancer.

All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy

The associations between physical fitness and cardiometabolic risk and body-size phenotypes in perimenopausal women

Objective: To study the association between physical fitness and body-size phenotypes, and to test which aspects of physical fitness show the greatest independent association with cardiometabolic risk in perimenopausal women. Study design: This cross-sectional study involved 228 women aged 53 +/- 5 years from southern Spain. Main outcome measurements: Physical fitness was assessed by means of the Senior Fitness Test Battery (additionally including handgrip strength and timed up-and-go tests). Anthropometry, resting heart rate, blood pressure and plasma markers of lipid, glycaemic and inflammatory status were measured by standard procedures. The harmonized definition of the 'metabolically healthy but obese' (MHO) phenotype was employed to classify individuals. Results: The overall prevalence of the MHO phenotype was 13% but was 43% among the obese women. Apart from traditional markers, metabolically healthy non-obese women had lower levels of C-reactive protein than women with the other phenotypes (p <0.001), and levels of glycosylated haemoglobin were lower in MHO women than in metabolically abnormal non-obese women (overall p = 0.004). Most of the components of physical fitness differed with body-size phenotypes. The 6-min walk and the back-scratch tests presented the most robust differences (both p <0.001). Moreover, the women's performance on the back-scratch (beta = 0.32; p <0.001) and the 6-min walk (beta = 0.22; p = 0.003) tests was independently associated with the clustered cardiometabolic risk. The back-scratch test explained 10% of the variability (step 1, p <0.001), and the final model, which also included the 6-min walk test (step 2, p = 0.003), explained 14% of the variability. Conclusion: Low upper-body flexibility was the most important fitness indicator of cardiometabolic risk in perimenopausal women, but cardiorespiratory fitness also played an important role. (C) 2016 Elsevier Ireland Ltd. All rights reserved