Infectious pathogens are strong and modifiable causes of cancer. The aim of this study was to improve estimates of the global and regional burden of infection-attributable cancers to inform research ...priorities and facilitate prevention efforts.
We used the GLOBOCAN 2018 database of cancer incidence and mortality rates and estimated the attributable fractions and global incidence for specific anatomical cancer sites, subsites, or histological subtypes known to be associated with ten infectious pathogens classified as human carcinogens. We calculated absolute numbers and age-standardised incidence rates (ASIR) of infection-attributable cancers at the country level. Estimates were stratified for sex, age group, and country, and were aggregated according to geographical regions and World Bank income groups.
We found that, for 2018, an estimated 2·2 million infection-attributable cancer cases were diagnosed worldwide, corresponding to an infection-attributable ASIR of 25·0 cases per 100 000 person-years. Primary causes were Helicobacter pylori (810 000 cases, ASIR 8·7 cases per 100 000 person-years), human papillomavirus (690 000, 8·0), hepatitis B virus (360 000, 4·1) and hepatitis C virus (160 000, 1·7). Infection-attributable ASIR was highest in eastern Asia (37·9 cases per 100 000 person-years) and sub-Saharan Africa (33·1), and lowest in northern Europe (13·6) and western Asia (13·8). China accounted for a third of worldwide cancer cases attributable to infection, driven by high ASIR of H pylori (15·6) and hepatitis B virus (11·7) infection. The cancer burden attributed to human papillomavirus showed the clearest relationship with country income level (from ASIR of 6·9 cases per 100 000 person-years in high-income countries to 16·1 in low-income countries).
Infection-attributable cancer incidence, in addition to the absolute number of cases, allows for refined geographic analyses and identification of populations with a high infection-associated cancer burden. When cancer prevention is largely considered in a non-communicable disease context, there is a crucial need for resources directed towards cancer prevention programmes that target infection, particularly in high-risk populations. Such interventions can markedly reduce the increasing cancer burden and associated mortality.
International Agency for Research on Cancer.
Seeds and the Art of Genome Maintenance Waterworth, Wanda M; Bray, Clifford M; West, Christopher E
Frontiers in plant science,
05/2019, Volume:
10
Journal Article
Peer reviewed
Open access
Successful germination represents a crucial developmental transition in the plant lifecycle and is important both for crop yields and plant survival in natural ecosystems. However, germination ...potential decreases during storage and seed longevity is a key determinant of crop production. Decline in germination vigor is initially manifest as an increasing delay to radicle emergence and the completion of germination and eventually culminating in loss of seed viability. The molecular mechanisms that determine seed germination vigor and viability remain obscure, although deterioration in seed quality is associated with the accumulation of damage to cellular structures and macromolecules including lipids, protein, and nucleic acids. In desiccation tolerant seeds, desiccation/rehydration cycles and prolonged periods in the dry quiescent state are associated with remarkable levels of stress to the embryo genome which can result in mutagenesis of the genetic material, inhibition of transcription and replication and delayed growth and development. An increasing number of studies are revealing DNA damage accumulated in the embryo genome, and the repair capacity of the seed to reverse this damage, as major factors that determine seed vigor and viability. Recent findings are now establishing important roles for the DNA damage response in regulating germination, imposing a delay to germination in aged seed to minimize the deleterious consequences of DNA damage accumulated in the dry quiescent state. Understanding the mechanistic basis of seed longevity will underpin the directed improvement of crop varieties and support preservation of plant genetic resources in seed banks.
Seeds are important to agriculture and conservation of plant biodiversity. In agriculture, seed germination performance is an important determinant of crop yield, in particular under adverse climatic ...conditions. Deterioration in seed quality is associated with the accumulation of cellular damage to macromolecules including lipids, protein, and DNA. Mechanisms that mitigate the deleterious cellular damage incurred in the quiescent state and in cycles of desiccation–hydration are crucial for the maintenance of seed viability and germination vigour. In early-imbibing seeds, damage to the embryo genome must be repaired prior to initiation of cell division to minimize growth inhibition and mutation of genetic information. Here we review recent advances that have established molecular links between genome integrity and seed quality. These studies identified that maintenance of genome integrity is particularly important to the seed stage of the plant lifecycle, revealing new insight into the physiological roles of plant DNA repair and recombination mechanisms. The high conservation of DNA repair and recombination factors across plant species underlines their potential as promising targets for the improvement of crop performance and development of molecular markers for prediction of seed vigour.
Genome integrity is crucial for cellular survival and the faithful transmission of genetic information. The eukaryotic cellular response to DNA damage is orchestrated by the DNA damage checkpoint ...kinases ATAXIA TELANGIECTASIA MUTATED (ATM) and ATM AND RAD3-RELATED (ATR). Here we identify important physiological roles for these sensor kinases in control of seed germination. We demonstrate that double-strand breaks (DSBs) are rate-limiting for germination. We identify that desiccation tolerant seeds exhibit a striking transcriptional DSB damage response during germination, indicative of high levels of genotoxic stress, which is induced following maturation drying and quiescence. Mutant atr and atm seeds are highly resistant to aging, establishing ATM and ATR as determinants of seed viability. In response to aging, ATM delays germination, whereas atm mutant seeds germinate with extensive chromosomal abnormalities. This identifies ATM as a major factor that controls germination in aged seeds, integrating progression through germination with surveillance of genome integrity. Mechanistically, ATM functions through control of DNA replication in imbibing seeds. ATM signaling is mediated by transcriptional control of the cell cycle inhibitor SIAMESE-RELATED 5, an essential factor required for the aging-induced delay to germination. In the soil seed bank, seeds exhibit increased transcript levels of ATM and ATR, with changes in dormancy and germination potential modulated by environmental signals, including temperature and soil moisture. Collectively, our findings reveal physiological functions for these sensor kinases in linking genome integrity to germination, thereby influencing seed quality, crucial for plant survival in the natural environment and sustainable crop production.
DNA repair is important for maintaining genome integrity. In plants, DNA damage accumulated in the embryo of seeds is repaired early in imbibition, and is important for germination performance and ...seed longevity. An essential step in most repair pathways is the DNA ligase-mediated rejoining of single- and double-strand breaks. Eukaryotes possess multiple DNA ligase enzymes, each having distinct roles in cellular metabolism. Here, we report the characterization of DNA LIGASE VI, which is only found in plant species. The primary structure of this ligase shows a unique N-terminal region that contains a β-CASP motif, which is found in a number of repair proteins, including the DNA double-strand break (DSB) repair factor Artemis. Phenotypic analysis revealed a delay in the germination of atlig6 mutants compared with wild-type lines, and this delay becomes markedly exacerbated in the presence of the genotoxin menadione. Arabidopsis atlig6 and atlig6 atlig4 mutants display significant hypersensitivity to controlled seed ageing, resulting in delayed germination and reduced seed viability relative to wild-type lines. In addition, atlig6 and atlig6 atlig4 mutants display increased sensitivity to low-temperature stress, resulting in delayed germination and reduced seedling vigour upon transfer to standard growth conditions. Seeds display a rapid transcriptional DNA DSB response, which is activated in the earliest stages of water imbibition, providing evidence for the accumulation of cytotoxic DSBs in the quiescent seed. These results implicate AtLIG6 and AtLIG4 as major determinants of Arabidopsis seed quality and longevity.
DNA damage threatens the integrity of the genome and has potentially lethal consequences for the organism. Plant DNA is under continuous assault from endogenous and environmental factors and ...effective detection and repair of DNA damage are essential to ensure the stability of the genome. One of the most cytotoxic forms of DNA damage are DNA double-strand breaks (DSBs) which fragment chromosomes. Failure to repair DSBs results in loss of large amounts of genetic information which, following cell division, severely compromises daughter cells that receive fragmented chromosomes. This review will survey recent advances in our understanding of plant responses to chromosomal breaks, including the sources of DNA damage, the detection and signalling of DSBs, mechanisms of DSB repair, the role of chromatin structure in repair, DNA damage signalling and the link between plant recombination pathways and transgene integration. These mechanisms are of critical importance for maintenance of plant genome stability and integrity under stress conditions and provide potential targets for the improvement of crop plants both for stress resistance and for increased precision in the generation of genetically improved varieties.
As obligate phototrophs, plants harness energy from sunlight to split water, producing oxygen and reducing power. This lifestyle exposes plants to particularly high levels of genotoxic stress that ...threatens genomic integrity, leading to mutation, developmental arrest and cell death. Plants, which with algae are the only photosynthetic eukaryotes, have evolved very effective pathways for DNA damage signalling and repair, and this review summarises our current understanding of these processes in the responses of plants to genotoxic stress. We also identify how the use of new and emerging technologies can complement established physiological and ecological studies to progress the application of this knowledge in biotechnology.
We publish three Roadmaps on photonic, electronic and atomic collision physics in order to celebrate the 60th anniversary of the ICPEAC conference. In Roadmap II we focus on electron and antimatter ...interactions. Modern theoretical and experimental approaches provide detailed insight into the many body quantum dynamics of leptonic collisions with targets of varying complexity ranging from neutral and charged atoms to large biomolecules and clusters. These developments have been driven by technological progress and by the needs of adjacent areas of science such as astrophysics, plasma physics and radiation biophysics. This Roadmap aims at looking back along the road, explaining the evolution of the field, and looking forward, collecting contributions from eighteen leading groups from the field.
DNA ligase enzymes catalyse the joining of adjacent polynucleotides and as such play important roles in DNA replication and repair pathways. Eukaryotes possess multiple DNA ligases with distinct ...roles in DNA metabolism, with clear differences in the functions of DNA ligase orthologues between animals, yeast and plants. DNA ligase 1, present in all eukaryotes, plays critical roles in both DNA repair and replication and is indispensable for cell viability.
Knockout mutants of atlig1 are lethal. Therefore, RNAi lines with reduced levels of AtLIG1 were generated to allow the roles and importance of Arabidopsis DNA ligase 1 in DNA metabolism to be elucidated. Viable plants were fertile but displayed a severely stunted and stressed growth phenotype. Cell size was reduced in the silenced lines, whilst flow cytometry analysis revealed an increase of cells in S-phase in atlig1-RNAi lines relative to wild type plants. Comet assay analysis of isolated nuclei showed atlig1-RNAi lines displayed slower repair of single strand breaks (SSBs) and also double strand breaks (DSBs), implicating AtLIG1 in repair of both these lesions.
Reduced levels of Arabidopsis DNA ligase 1 in the silenced lines are sufficient to support plant development but result in retarded growth and reduced cell size, which may reflect roles for AtLIG1 in both replication and repair. The finding that DNA ligase 1 plays an important role in DSB repair in addition to its known function in SSB repair, demonstrates the existence of a previously uncharacterised novel pathway, independent of the conserved NHEJ. These results indicate that DNA ligase 1 functions in both DNA replication and in repair of both ss and dsDNA strand breaks in higher plants.
HIV enhances human papillomavirus (HPV)-induced carcinogenesis. However, the contribution of HIV to cervical cancer burden at a population level has not been quantified. We aimed to investigate ...cervical cancer risk among women living with HIV and to estimate the global cervical cancer burden associated with HIV.
We did a systematic literature search and meta-analysis of five databases (PubMed, Embase, Global Health CABI.org, Web of Science, and Global Index Medicus) to identify studies analysing the association between HIV infection and cervical cancer. We estimated the pooled risk of cervical cancer among women living with HIV across four continents (Africa, Asia, Europe, and North America). The risk ratio (RR) was combined with country-specific UNAIDS estimates of HIV prevalence and GLOBOCAN 2018 estimates of cervical cancer to calculate the proportion of women living with HIV among women with cervical cancer and population attributable fractions and age-standardised incidence rates (ASIRs) of HIV-attributable cervical cancer.
24 studies met our inclusion criteria, which included 236 127 women living with HIV. The pooled risk of cervical cancer was increased in women living with HIV (RR 6·07, 95% CI 4·40–8·37). Globally, 5·8% (95% CI 4·6–7·3) of new cervical cancer cases in 2018 (33 000 new cases, 95% CI 26 000–42 000) were diagnosed in women living with HIV and 4·9% (95% CI 3·6–6·4) were attributable to HIV infection (28 000 new cases, 20 000–36 000). The most affected regions were southern Africa and eastern Africa. In southern Africa, 63·8% (95% CI 58·9–68·1) of women with cervical cancer (9200 new cases, 95% CI 8500–9800) were living with HIV, as were 27·4% (23·7–31·7) of women in eastern Africa (14 000 new cases, 12 000–17 000). ASIRs of HIV-attributable cervical cancer were more than 20 per 100 000 in six countries, all in southern Africa and eastern Africa.
Women living with HIV have a significantly increased risk of cervical cancer. HPV vaccination and cervical cancer screening for women living with HIV are especially important for countries in southern Africa and eastern Africa, where a substantial HIV-attributable cervical cancer burden has added to the existing cervical cancer burden.
WHO, US Agency for International Development, and US President's Emergency Plan for AIDS Relief.
PDF
