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"Leon, David"
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Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults
2014
High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers.
With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects.
5·24 million individuals were included; 166 955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m2 increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56–1·69; p<0·0001), gallbladder (1·31, 1·12–1·52; p<0·0001), kidney (1·25, 1·17–1·33; p<0·0001), cervix (1·10, 1·03–1·17; p=0·00035), thyroid (1·09, 1·00–1·19; p=0·0088), and leukaemia (1·09, 1·05–1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12–1·27), colon (1·10, 1·07–1·13), ovarian (1·09, 1.04–1.14), and postmenopausal breast cancers (1·05, 1·03–1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95–1·00; premenopausal breast cancer 0·89, 0·86–0·92) and in never-smokers (prostate 0·96, 0·93–0·99; premenopausal breast cancer 0·89, 0·85–0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93–1·05; oral cavity 1·07, 0·91–1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m2 population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI.
BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups.
National Institute for Health Research, Wellcome Trust, and Medical Research Council.
Journal Article
Self-reported health as a predictor of mortality: A cohort study of its relation to other health measurements and observation time
2020
Self-reported health (SRH) is widely used as an epidemiological instrument given the changes in public health since its introduction in the 1980s. We examined the association between SRH and mortality and how this is affected by time and health measurements in a prospective cohort study using repeated measurements and physical examinations of 11652 men and 12684 women in Tromsø, Norway. We used Cox proportional hazard regression to estimate hazard ratios (HRs) of death for SRH, controlling for pathology, biometrics, smoking, sex and age. SRH predicted mortality independently of other, more objective health measures. Higher SRH was strongly associated with lower mortality risk. Poor SRH had HR 2.51 (CI: 2.19, 2.88). SRH is affected by disease, mental health and other risk factors, but these factors had little impact on HRs (Poor SRH: HR 1.99; CI: 1.72, 2.31). SRH predicted mortality, but with a time-dependent effect. Time strongly affected the hazard ratio for mortality, especially after ten-year follow-up (Poor SRH HR 3.63 at 0–5 years decreased to HR 1.58 at 15–21 years). SRH has both methodological and clinical value. It should not be uncritically utilised as a replacement instrument when measures of physical illness and other objective health measures are lacking.
Journal Article
Widening East-West inequality in life expectancy in Europe during the COVID-19 pandemic: An international comparative study
by
Jdanov, Dmitri
,
Islam, Nazrul
,
Leon, David A.
in
Analysis
,
Biology and Life Sciences
,
Communism
2026
For decades, life expectancy in Eastern Europe has lagged behind that in Western Europe, although the gap has narrowed since the mid-2000s. We examined the impact of the COVID-19 pandemic on these long-term trends by estimating and decomposing East-West differences in excess mortality and life expectancy losses. Regression models were used to explore the contribution of multiple factors to the observed differences. While excess mortality was initially low in Eastern Europe, partly due to lower air connectivity, by October 2020 and throughout 2021, the region experienced significantly higher life expectancy losses than Western Europe. These differences could not be attributed to greater frailty in the Eastern European populations. Rather, lower vaccination coverage and less trust in government in Eastern Europe explained about half of the gap in 2021. After the peak of the pandemic, the East-West gap in life expectancy began to narrow again. Our findings highlight that the factors behind the East-West differences in the timing and severity of pandemic-related mortality may have their ultimate origins in differences between societies that were established during the Cold War. Strengthening public health infrastructure and social trust should be considered to mitigate the unequal impact of future crises.
Journal Article
Current and projected regional economic impacts of heatwaves in Europe
by
Casanueva, Ana
,
Nybo, Lars
,
Standardi, Gabriele
in
704/844/2739/2807
,
704/844/841
,
704/844/843
2021
Extreme heat undermines the working capacity of individuals, resulting in lower productivity, and thus economic output. Here we analyse the present and future economic damages due to reduced labour productivity caused by extreme heat in Europe. For the analysis of current impacts, we focused on heatwaves occurring in four recent anomalously hot years (2003, 2010, 2015, and 2018) and compared our findings to the historical period 1981–2010. In the selected years, the total estimated damages attributed to heatwaves amounted to 0.3–0.5% of European gross domestic product (GDP). However, the identified losses were largely heterogeneous across space, consistently showing GDP impacts beyond 1% in more vulnerable regions. Future projections indicate that by 2060 impacts might increase in Europe by a factor of almost five compared to the historical period 1981–2010 if no further mitigation or adaptation actions are taken, suggesting the presence of more pronounced effects in the regions where these damages are already acute.
Heatwaves are becoming increasingly frequent and more intense, causing severe economic impacts through reduced labour productivity. Here, the authors show that economic damages in Europe exceed 1% of the GDP in vulnerable areas, which might increase by a factor of almost five in the medium term without climate action.
Journal Article
Plant functional groups associate with distinct arbuscular mycorrhizal fungal communities
by
Öpik, Maarja
,
Soudzilovaskaia, Nadejda A.
,
Zobel, Martin
in
arbuscular mycorrhizal symbiosis
,
Arbuscular mycorrhizas
,
Community composition
2020
• The benefits of the arbuscular mycorrhizal (AM) symbiosis between plants and fungi are modulated by the functional characteristics of both partners. However, it is unknown to what extent functionally distinct groups of plants naturally associate with different AM fungi.
• We reanalysed 14 high-throughput sequencing data sets describing AM fungal communities associating with plant individuals (2427) belonging to 297 species. We examined how root-associating AM fungal communities varied between plants with different growth forms, photosynthetic pathways, CSR (competitor, stress-tolerator, ruderal) strategies, mycorrhizal statuses and N-fixing statuses.
• AM fungal community composition differed in relation to all studied plant functional groups. Grasses, C₄ and nonruderal plants were characterised by high AM fungal alpha diversity, while C₄, ruderal and obligately mycorrhizal plants were characterised by high beta diversity. The phylogenetic diversity of AM fungi, a potential surrogate for functional diversity, was higher among forbs than other plant growth forms. Putatively ruderal (previously cultured) AM fungi were disproportionately associated with forbs and ruderal plants. There was phylogenetic correlation among AM fungi in the degree of association with different plant growth forms and photosynthetic pathways.
• Associated AM fungal communities constitute an important component of plant ecological strategies. Functionally different plants associate with distinct AM fungal communities, linking mycorrhizal associations with functional diversity in ecosystems.
Journal Article
Untreated hypertension in Russian 35-69 year olds – a cross-sectional study
2020
The Russian Federation has among the highest rates of cardiovascular disease (CVD) in the world and a high rate of untreated hypertension remains an important risk factor. Understanding who is at greatest risk is important to inform approaches to primary prevention.
2,353 hypertensive 35-69 year olds were selected from a population-based study, Know Your Heart, conducted in Arkhangelsk and Novosibirsk, Russian Federation, 2015-2018. The associations between untreated hypertension and a range of co-variates related to socio-demographics, health, and health behaviours were examined.
The age-standardised prevalence of untreated hypertension was 51.1% (95% CI 47.8-54.5) in males, 28.8% (25.4-32.5) in females, and 40.0% (37.5-42.5) overall. The factors associated with untreated hypertension relative to treated hypertension were younger ages, self-rated general health as very good-excellent, not being obese, no history of CVD events, no evidence of diabetes or chronic kidney disease, and not seeing a primary care doctor in the past year as well as problem drinking for women and working full time, lower education, and smoking for men.
The study found relatively high prevalence of untreated hypertension, especially, in men. Recent initiatives to strengthen primary care provision and implementation of a general health check programme (dispansarisation) are promising, although further studies should evaluate other, potentially more effective strategies tailored to the particular circumstances of this population.
Journal Article
Deep learning-derived cardiovascular age shares a genetic basis with other cardiac phenotypes
by
Attia, Zachi I.
,
Friedman, Paul A.
,
Phelan, Jody E.
in
631/114/1305
,
631/208/205/2138
,
692/4019/592/2727
2022
Artificial intelligence (AI)-based approaches can now use electrocardiograms (ECGs) to provide expert-level performance in detecting heart abnormalities and diagnosing disease. Additionally, patient age predicted from ECGs by AI models has shown great potential as a biomarker for cardiovascular age, where recent work has found its deviation from chronological age (“delta age”) to be associated with mortality and co-morbidities. However, despite being crucial for understanding underlying individual risk, the genetic underpinning of delta age is unknown. In this work we performed a genome-wide association study using UK Biobank data (n=34,432) and identified eight loci associated with delta age (
p
≤
5
×
10
-
8
), including genes linked to cardiovascular disease (CVD) (e.g.
SCN5A
) and (heart) muscle development (e.g.
TTN
). Our results indicate that the genetic basis of cardiovascular ageing is predominantly determined by genes directly involved with the cardiovascular system rather than those connected to more general mechanisms of ageing. Our insights inform the epidemiology of CVD, with implications for preventative and precision medicine.
Journal Article