DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity

Worldwide trends in population-based survival for children, adolescents, and young adults diagnosed with leukaemia, by subtype, during 2000–14 (CONCORD-3) : analysis of individual data from 258 cancer registries in 61 countries

Background Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0–14 years) and adults (aged 15–99 years) diagnosed with a haematological malignancy during 2000–14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0–24 years). Methods We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0–14 years), adolescents (15–19 years), and young adults (20–24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. Findings 164563 young people were included in this analysis: 121328 (73·7%) children, 22963 (14·0%) adolescents, and 20272 (12·3%) young adults. In 2010–14, the most common subtypes were lymphoid leukaemia (28205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010–14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000–14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. Interpretation This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group.peer-reviewe

Global survival trends for brain tumors, by histology: analysis of individual records for 556,237 adults diagnosed in 59 countries during 2000–2014 (CONCORD-3)

Background: Survival is a key metric of the effectiveness of a health system in managing cancer. We set out to provide a comprehensive examination of worldwide variation and trends in survival from brain tumors in adults, by histology. Methods: We analyzed individual data for adults (15–99 years) diagnosed with a brain tumor (ICD-O-3 topography code C71) during 2000–2014, regardless of tumor behavior. Data underwent a 3-phase quality control as part of CONCORD-3. We estimated net survival for 11 histology groups, using the unbiased nonparametric Pohar Perme estimator. Results: The study included 556,237 adults. In 2010–2014, the global range in age-standardized 5-year net survival for the most common sub-types was broad: in the range 20%–38% for diffuse and anaplastic astrocytoma, from 4% to 17% for glioblastoma, and between 32% and 69% for oligodendroglioma. For patients with glioblastoma, the largest gains in survival occurred between 2000–2004 and 2005–2009. These improvements were more noticeable among adults diagnosed aged 40–70 years than among younger adults. Conclusions: To the best of our knowledge, this study provides the largest account to date of global trends in population-based survival for brain tumors by histology in adults. We have highlighted remarkable gains in 5-year survival from glioblastoma since 2005, providing large-scale empirical evidence on the uptake of chemoradiation at population level. Worldwide, survival improvements have been extensive, but some countries still lag behind. Our findings may help clinicians involved in national and international tumor pathway boards to promote initiatives aimed at more extensive implementation of clinical guidelines

A cross-sectional analysis of ex-smokers and characteristics associated with quitting smoking: The Polish Norwegian Study (PONS)

Tobacco smoking remains a number one preventable risk factor of premature death worldwide. Findings of recent research show concurrent trends of lung cancer deaths in males and females in Europe. Although lung cancer death rates are consistently decreasing in male population, in women an upward trend is observed. The burden of tobacco-related harm can be prevented by smoking cessation. The main goal of this analysis is to identify the crucial correlates of successful smoking cessation in the middle-aged Polish population. The data came from 13 172 survey participants south-eastern part of Poland as part of the PONS cohort study established in 2010. A total of 6998 records of those who were either ex-smokers or current smokers at baseline were analyzed. We applied logistic regression and adjusted for sociodemographic covariates and health determinants. Characteristics related to being an ex-smoker as opposed to a current smoker included: older age [men: odds ratio (OR)=1.03, 95% confidence interval (CI)=1.01-1.05; women: OR=1.05, 95% CI=1.03-1.07], being married or living together, having secondary (OR=1.51, 95% CI=1.14-1.99) or higher (OR=2.30, 95% CI=1.75-3.18) education (women), full-time employment (men), alcohol consumer (women), being overweight (men: OR=2.85, 95% CI=2.26-3.59; women: OR=1.60, 95% CI=1.36-1.87) or obese (men: OR=3.47, 95% CI=2.67-4.51; women: OR=2.99, 95% CI=2.45-3.65), having normal fasting glucose and cholesterol blood level without any treatment (women), assessing their own health highly (9-10, on the scale from 1 to 10) and having at least one accompanying chronic disease (women, OR=1.25, 95% CI=1.07-1.45). These findings provide valuable information on characteristics of ex-smokers as well as behavioral and sociodemographic predictors of successful cessation. Such data expand our knowledge and can be used to design a more comprehensive and targeted group-specific tobacco control policy focused on increasing the number of ex-smokers

Tobacco smoking in countries of the European Union.

Background: Existing smoking prevalence comparisons between the 'old' and 'new' members of the European Union (EU) give a misleading picture because of differences in methodology. A major EU project designed to find ways of closing the health gap between the member states, included the first ever comparison of smoking prevalence between these countries using a methodology that minimises potential biases. Methods: A detailed analysis of methods and data from the most recent nationwide studies was conducted in the adult population of 27 countries of the European Union and Russia as an external comparator. To maximise comparability, daily smoking in the age range 20-64 was used. Prevalence of current daily smoking, former smoking and never smoking were age-standardised and calculated separately for males and females. Findings: The European map of smoking prevalence shows that male smoking prevalence is much higher in the new than the old members of the EU, whereas in females the reverse is true, but there are also very large differences in smoking rates between particular countries within the same region. Sweden clearly has the lowest prevalence, and the prevalence in the United Kingdom (UK) at the time of the surveys emerges as near the average for old-Europe but higher than, for example, Ireland. Interpretation: Restricting the analysis to daily smokers aged 20-64 produces a map of Europe in which variation in prevalence between individual countries within regions is as important as variation across regions. Survey methods need to be harmonised across countries to enable comparisons involving all ages and non-daily as well as daily smokers

Liver cirrhosis mortality in Europe, with special attention to Central and Eastern Europe

Background and Aims: Over the last decades, Europe has experienced dramatic changes in the geographical variation of liver cirrhosis rates. We attempt to provide a comprehensive analysis of patterns and trends in liver cirrhosis mortality in European countries and regions. Methods: Age-standardized (world standard) liver cirrhosis mortality rates per 100,000 person-years at ages 20-64 for 35 separate countries were computed using the World Health Organization Mortality Database. Results: In the analyzed period (1959-2002), a very strong East-to-West gradient in mortality rates was observed. An increase of the burden of mortality due to liver cirrhosis appeared in Eastern Europe in two specific areas: South-eastern Europe and North-eastern Europe. In the first group of countries, liver cirrhosis mortality was 10-20 times higher than in most other European states, levels never before observed in Europe. In the countries of North-eastern Europe (former Soviet Union countries) liver cirrhosis mortality was characterized by dramatic changes (both positive and negative) in specific periods of time. Conclusions: Despite the fact that the etiology of liver cirrhosis is multifactorial, it seems that alcohol drinking is the factor that best explains the observed patterns in frequency of this disease in Europe. Alcohol control policies in Central and Eastern Europe could lead to an appreciable reduction of premature mortality from liver cirrhosis. Copyrigh

Alcohol accounts for a high proportion of premature mortality in central and eastern Europe

Background: There is a west-east mortality gradient in Europe, more pronounced in men. The objective of this article was to quantify the contribution of alcohol use to the gap in premature adult mortality between three old (France, Sweden and United Kingdom) and four new (Czech Republic, Hungary, Lithuania and Poland) European Union (EU) member states for the year 2002. Russia was added as an external comparator. Methods: Exposure data were taken from surveys and per capita consumption records from the World Health Organization (WHO) Global Alcohol Database. Mortality data were taken from the WHO databank. The risk relationships were taken from published meta-analyses and from the WHO Comparative Risk Assessment project. Alcohol exposure and relative risk information was combined to derive alcohol-attributable fractions for relevant causes of premature mortality. Results: Alcohol consumption was responsible for 14.6% of all premature adult mortality in the eight countries, 17.3% in men and 8.0% in women. This proportion was clearly higher in the new EU member states and Russia compared with the comparison countries from the old EU. For men, Russia with 29.0 alcohol attributable premature deaths per 10 000 population had a more than 10-fold higher rate compared with Sweden (2.7 deaths/10 000). For women, the ratio between Hungary (5.0 alcohol-attributable deaths/10 000) and Russia (4.7 deaths/10 000) compared with Sweden (0.5 deaths/10 000) was almost as high, but the rates were much lower. The Czech Republic and Poland showed proportionally less alcohol-attributable premature mortality than the other new EU member states or Russia for both genders, which, however, was still higher than in any of the old EU member states. Conclusions: Alcohol is a strong contributor to the health gap between western and central and eastern Europe, with both average volume of consumption and patterns of drinking contributing to burden of disease and injury. Alcohol also contributes substantially to male-female differences in mortality and life expectancy. However, there are feasible and cost-effective measures to reduce alcohol-related burden that should be implemented in central and eastern Europe. \ua9 The Author 2007; all rights reserved