Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden

Positive selection of human cells lacking several transformation parameters from an SV40-transformed culture by means of parvovirus H-1

The simian virus 40 (SV40)-transformed, newborn human kidney cell line NB-F was found to be heterogenous with respect to its sensitivity to parvovirus H-1. The majority of the cells sustain a productive H-1 infection which eventually causes their lysis. Yet, a small fraction of the cells appears to be much less susceptible to H-1. Such a resistance to H-1 infection is a stable, transmissible property of this sub-population of cells which was denoted NB-FR. The heterogeneity of NB-F cells is also apparent from the distribution of their karyotypes, which is bimodal and peaks at 114 and 46 chromosomes/cell. In contrast, the great majority of NB-FR cells contain 41-50 chromosomes. H-1-resistant and sensitive cells appear to be related in several respects: they both contain morphologically human chromosomes as well as multiple SV40 DNA inserts, and could not be distinguished by isoenzyme typing. It was investigated whether the degree of sensitivity to H-1 infection correlated with other phenotypic properties of the human cell derivatives. NB-F cultures exhibit a series of transformation parameters, such as SV40 T-antigen expression, poor contact inhibition, clonogenicity in semi-solid medium and high lectin agglutinability, which are all much reduced or even undetectable in NB-FR cells. These observations suggest that cell susceptibility to H-1 segregates with marker(s) of in vitro malignant transformation. Moreover, the data indicate that parvoviruses can be used to preferentially remove transformants from a mixed culture of normal and transformed cells. © 1988 IRL Press Ltd.SCOPUS: ar.jinfo:eu-repo/semantics/publishe