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Single body mass index (BMI) measurements have been associated with increased risk of 13 cancers. Whether life course adiposity-related exposures are more relevant cancer risk factors than baseline BMI (ie, at start of follow-up for disease outcome) remains unclear. We conducted a cohort study from 2009 until 2018 with population-based electronic health records in Catalonia, Spain. We included 2,645,885 individuals aged ≥40 years and free of cancer in 2009. After 9 years of follow-up, 225,396 participants were diagnosed with cancer. This study shows that longer duration, greater degree, and younger age of onset of overweight and obesity during early adulthood are positively associated with risk of 18 cancers, including leukemia, non-Hodgkin lymphoma, and among never-smokers, head and neck, and bladder cancers which are not yet considered as obesity-related cancers in the literature. Our findings support public health strategies for cancer prevention focussing on preventing and reducing early overweight and obesity. Here, the authors show that longer duration and greater degree of overweight and obesity during early adulthood as well as younger age of onset of a high body mass index are associated with a higher risk of 18 cancer types.

Background A high body mass index (BMI) has been associated with increased risk of several cancers; however, whether BMI is related to a larger number of cancers than currently recognized is unclear. Moreover, whether waist circumference (WC) is more strongly associated with specific cancers than BMI is not well established. We aimed to investigate the associations between BMI and 26 cancers accounting for non-linearity and residual confounding by smoking status as well as to compare cancer risk estimates between BMI and WC. Methods Prospective cohort study with population-based electronic health records from Catalonia, Spain. We included 3,658,417 adults aged ≥ 18 years and free of cancer at baseline between 2006 and 2017. Our main outcome measures were cause-specific hazard ratios (HRs) with 99% confidence intervals (CIs) for incident cancer at 26 anatomical sites. Results After a median follow-up time of 8.3 years, 202,837 participants were diagnosed with cancer. A higher BMI was positively associated with risk of nine cancers (corpus uteri, kidney, gallbladder, thyroid, colorectal, breast post-menopausal, multiple myeloma, leukemia, non-Hodgkin lymphoma) and was positively associated with three additional cancers among never smokers (head and neck, brain and central nervous system, Hodgkin lymphoma). The respective HRs (per 5 kg/m 2 increment) ranged from 1.04 (99%CI 1.01 to 1.08) for non-Hodgkin lymphoma to 1.49 (1.45 to 1.53) for corpus uteri cancer. While BMI was negatively associated to five cancer types in the linear analyses of the overall population, accounting for non-linearity revealed that BMI was associated to prostate cancer in a U-shaped manner and to head and neck, esophagus, larynx, and trachea, bronchus and lung cancers in an L-shaped fashion, suggesting that low BMIs are an approximation of heavy smoking. Of the 291,305 participants with a WC measurement, 27,837 were diagnosed with cancer. The 99%CIs of the BMI and WC point estimates (per 1 standard deviation increment) overlapped for all cancers. Conclusions In this large Southern European study, a higher BMI was associated with increased risk of twelve cancers, including four hematological and head and neck (only among never smokers) cancers. Furthermore, BMI and WC showed comparable estimates of cancer risk associated with adiposity.

•The prevalence of obesity is increasing and only in a few countries it starts to flatten.•As a consequence of the global rise of obesity, the current and the future burden of cancers related to obesity are rising.•Not only affecting the occurrence of cancer, the increasing prevalence of obesity also affects prognosis among cancer survivors.•The prevention of the obesity pandemic is complex and requires a locally tailored approach to reduce harms on cancers and other diseases. In view of the growing global obesity epidemic, this paper reviews the relation between recent trends in body mass index (BMI) and the changing profile of cancer worldwide. By examining seven selected countries, each representing a world region, a pattern of increasing BMI with region and gender-specific diversity is noted: increasing levels of BMI were most pronounced in the Middle East (Saudi Arabia), rather modest in Eastern Asia (India) and generally more rapid in females than in males. This observation translates into a disproportionate distribution of cancer attributable to high levels of BMI, ranging by sex from 4–9% in Saudi Arabia and from 0.2–1.2% in India. Overweight and obesity may also influence cancer outcomes, and hence have a varying impact on cancer survival and death in different world regions. Future challenges in cancer studies exploring the association with overweight and obesity concern the measurement of adiposity and its potentially cumulative effect over the life course. Given the limitations of BMI as an imperfect measure of body fatness, routine anthropometric data collection needs to be extended to develop more informative measures, such as waist circumference in settings where the gold standard tools remain unaffordable. Furthermore, questions surrounding the dose-response and timing of obesity and their associations with cancer remain to be answered. Improved surveillance of health risk factors including obesity as well as the scale and profile of cancer in every country of the world is urgently needed. This will enable the design of cost-effective actions to curb the growing burden of cancer related to excess body weight.

Background: It has long been proposed that albumin, bilirubin and uric acid may inhibit cancer development due to their anti-oxidative properties. However, there is a lack of population-based studies on blood levels of these molecules and cancer risk. Methods: Associations between pre-diagnostic serum albumin, bilirubin and uric acid and the risks of common cancers as well as cancer death in the EPIC-Heidelberg cohort were evaluated by multivariable Cox regression analyses. A case–cohort sample including a random subcohort ( n =2739) and all incident cases of breast ( n =627), prostate ( n =554), colorectal ( n =256), and lung cancer ( n =195) as well as cancer death ( n =761) that occurred between baseline (1994–1998) and 2009 was used. Results: Albumin levels were inversely associated with breast cancer risk (hazard ratio Quartile 4 vs Quartile 1 (95% CI): 0.71 (0.51, 0.99), P linear trend =0.004) and overall cancer mortality (HR Q4 vs Q1 (95% CI): 0.64 (0.48, 0.86), P linear trend <0.001) after multivariable adjustment. Uric acid levels were also inversely associated with breast cancer risk (HR Q4 vs Q1 (95% CI): 0.72 (0.53, 0.99), P linear trend =0.043) and cancer mortality (HR Q4 vs Q1 (95% CI): 0.75 (0.58, 0.98), P linear trend =0.09). There were no significant associations between albumin or uric acid and prostate, lung and colorectal cancer. Serum bilirubin was not associated with any cancer end point. Conclusions: The present findings indicate that higher levels of albumin and uric acid are related to lower risks of breast cancer and cancer mortality. Further studies are needed to assess whether the observed associations are causal.

Background Cardiometabolic multimorbidity (CM) is an increasing public health and clinical concern. However, predictors for the development and prognosis of CM are poorly understood. The aims of this study were to investigate the relation between handgrip strength (HGS) and the risk of CM and to examine the association of HGS with all-cause mortality risk among patients with CM. Methods This prospective cohort study involved 493,774 participants from the UK Biobank. CM was defined as the simultaneous occurrence of two or more of the following conditions: type 2 diabetes, stroke, and coronary heart disease (CHD). Cox proportional hazards models were performed to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results During a median follow-up of 12.1 years, 4701 incident CM cases were documented among participants with none cardiometabolic disease at baseline. Compared with the fourth quartile (Q4), the multivariable adjusted HR (95% CI) value of Q1 of HGS for developing CM was 1.46 (1.34–1.60). In participants with one cardiometabolic disease at baseline, participants in Q1 of HGS also possessed higher risk of CM than those in Q4, with HRs (95% CIs) being 1.35 (1.23–1.49) in patients with type 2 diabetes, 1.23 (1.04–1.46) in patients with stroke, and 1.23 (1.11–1.36) in patients with CHD. For participants with CM at recruitment, HGS was also associated with the risk of all-cause mortality (Q1 vs. Q4 HR: 1.57, 95% CI: 1.36–1.80). Conclusions Our study provided novel evidence that HGS could be an independent predictor of morbidity and all-cause mortality of CM.

Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI < 18.5 kg/m 2 ) or obese (BMI ≥ 30 kg/m 2 ) categories, while the highest quartile of ABSI separated 18–39% of the individuals within each BMI category, which had 22–55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.

Background Mildly elevated bilirubin, a by-product of hemoglobin breakdown, might mitigate cardiometabolic risk factors including adiposity, dyslipidemia, and high blood pressure (BP). We investigated the cross-sectional relationship between (total) bilirubin and baseline cardiometabolic risk factors in 467,519 UK Biobank study participants. Methods We used multivariable-adjusted linear regression to estimate associations between bilirubin levels and risk factors of cardiometabolic diseases including body mass index (BMI), waist and hip circumferences (WC, HC), waist-to-hip ratio (WHR), fat mass (FM), and trunk FM, and the blood lipids: apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), apoB/apoA-I, lipoprotein (a), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), LDL/HDL, TC/HDL, triglycerides (TG). Log-transformed bilirubin was modelled with restricted cubic splines and predicted mean values with 99% confidence intervals (CI) for each risk marker were estimated, separately. Second, we applied principal component analysis (PCA) for dimension reduction to in turn six anthropometric traits (height, weight, BMI, WC, HC, and WHR) and all above lipids. Last, we estimated associations (99%CI) between bilirubin and three components of the metabolic syndrome, i.e. WC, TG, and BP using logistic regression. Results After multivariable adjustments, higher levels of bilirubin were inversely associated with indicators of general adiposity (BMI and FM) and of body fat distribution (WC, HC, WHR, and trunk FM) in both men and women. For example, women with mildly elevated bilirubin (95 th percentile equal to 15.0 µmol/L), compared to women with low bilirubin (5 th percentile equal to 4.5 µmol/L), had on average a 2.0 kg/m 2 (99% CI 1.9–2.1) lower BMI. Inverse associations were also observed with dyslipidemia among men and women. For example, mildly elevated bilirubin among men (95 th percentile equal to 19.4 µmol/L) compared to low levels of bilirubin (5 th percentile equal to 5.5 µmol/L) were associated with approx. 0.55 mmol/L (99% CI 0.53–0.56) lower TG levels, with similar inverse associations among women. Multiple-trait analyses using PCA confirmed single-trait analyses. Men and women with mildly elevated bilirubin levels ≥ 17.1 µmol/L, compared to low-normal bilirubin < 10 µmol/L had 13% (99% CI 8%–18%) and 11% (99% CI 4%–17%) lower odds of exceeding systolic BP levels of ≥ 130 mm Hg, respectively. Conclusions Higher levels of bilirubin were inversely associated with cardiometabolic risk factors including adiposity, dyslipidemia, and hypertension.

Abstract Context A comprehensive understanding of the association between body mass index (BMI) and coronavirus disease 2019 (COVID-19) is still lacking. Objective To investigate associations between BMI and risk of COVID-19 diagnosis, hospitalization with COVID-19, and death after a COVID-19 diagnosis or hospitalization (subsequent death), accounting for potential effect modification by age and sex. Design Population-based cohort study. Setting Primary care records covering >80% of the Catalan population, linked to regionwide testing, hospital, and mortality records from March to May 2020. Participants Adults (≥18 years) with at least 1 measurement of weight and height. Main outcome measures Hazard ratios (HR) for each outcome. Results We included 2 524 926 participants. After 67 days of follow-up, 57 443 individuals were diagnosed with COVID-19, 10 862 were hospitalized with COVID-19, and 2467 had a subsequent death. BMI was positively associated with being diagnosed and hospitalized with COVID-19. Compared to a BMI of 22 kg/m2, the HR (95% CI) of a BMI of 31 kg/m2 was 1.22 (1.19-1.24) for diagnosis and 1.88 (1.75-2.03) and 2.01 (1.86-2.18) for hospitalization without and with a prior outpatient diagnosis, respectively. The association between BMI and subsequent death was J-shaped, with a modestly higher risk of death among individuals with BMIs ≤ 19 kg/m2 and a more pronounced increasing risk for BMIs ≥ 40 kg/m2. The increase in risk for COVID-19 outcomes was particularly pronounced among younger patients. Conclusions There is a monotonic association between BMI and COVID-19 diagnosis and hospitalization risks but a J-shaped relationship with mortality. More research is needed to unravel the mechanisms underlying these relationships.

Background Whether cancer risk associated with a higher body mass index (BMI), a surrogate measure of adiposity, differs among adults with and without cardiovascular diseases (CVD) and/or type 2 diabetes (T2D) is unclear. The primary aim of this study was to evaluate separate and joint associations of BMI and CVD/T2D with the risk of cancer. Methods This is an individual participant data meta-analysis of two prospective cohort studies, the UK Biobank (UKB) and the European Prospective Investigation into Cancer and nutrition (EPIC), with a total of 577,343 adults, free of cancer, T2D, and CVD at recruitment. We used Cox proportional hazard regressions to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between BMI and incidence of obesity-related cancer and in turn overall cancer with a multiplicative interaction between BMI and the two cardiometabolic diseases (CMD). HRs and 95% CIs for separate and joint associations for categories of overweight/obesity and CMD status were estimated, and additive interaction was quantified through relative excess risk due to interaction (RERI). Results In the meta-analysis of both cohorts, BMI (per ~ 5 kg/m 2 ) was positively associated with the risk of obesity-related cancer among participants without a CMD (HR: 1.11, 95%CI: 1.07,1.16), among participants with T2D (HR: 1.11, 95% CI: 1.05,1.18), among participants with CVD (HR: 1.17, 95% CI: 1.11,1.24), and suggestively positive among those with both T2D and CVD (HR: 1.09, 95% CI: 0.94,1.25). An additive interaction between obesity (BMI ≥ 30 kg/m 2 ) and CVD with the risk of overall cancer translated into a meta-analytical RERI of 0.28 (95% CI: 0.09–0.47). Conclusions Irrespective of CMD status, higher BMI increased the risk of obesity-related cancer among European adults. The additive interaction between obesity and CVD suggests that obesity prevention would translate into a greater cancer risk reduction among population groups with CVD than among the general population.

Background Waist circumference and grip strength are each associated with type 2 diabetes (T2D) risk, but their joint associations have been less well studied. Methods We examined the separate and joint associations of waist circumference and grip strength with incident T2D among 483,578 adults aged 40–69 years (55% women) without T2D at baseline (2006–2010) from UK Biobank. Waist circumference was measured by trained staff and categorized using World Health Organization thresholds. Grip strength was assessed using a hydraulic dynamometer and categorized into age- and sex-specific tertiles. Incident T2D was ascertained through linkage to hospital inpatient records until 2022. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression, adjusting for sociodemographic, lifestyle, and clinical covariates. Results During 13.0 years of follow-up (6.3 million person-years), 30,240 participants (6.3%) developed T2D. Compared to individuals with low waist circumference (men: ≤ 94 cm, women: ≤ 80 cm), HRs were 2.11 (95% CI 2.03–2.19) for those with intermediate (men: 95–102 cm, women: 81–88 cm) and 5.48 (95% CI 5.30–5.66) for those with high waist circumference (men: > 102 cm, women: > 88 cm). Compared to individuals with high grip strength, HRs were 1.08 (95% CI 1.05–1.11) for those with intermediate and 1.35 (95% CI 1.32–1.39) for those with low grip strength. Joint analyses showed the highest risk among participants with the combination of high waist circumference and low grip strength (HR 7.68, 95% CI 7.22–8.17) compared to individuals with the combination of low waist circumference and high grip strength. Associations between waist circumference and T2D were stronger in women, whereas associations with grip strength were stronger in men. Both patterns were more pronounced among younger adults. Conclusions Waist circumference and grip strength were separately and jointly associated with T2D risk. The combination of high waist circumference and low grip strength conferred the greatest risk. Joint assessment of waist circumference and grip strength identifies individuals at particularly elevated risk and may inform preventive strategies, though formal evaluation of incremental predictive utility is needed.