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Background: Colorectal cancer (CRC) is the third-most-common cancer worldwide and its rates are increasing. Elevated body mass index (BMI) is an established risk factor for CRC, although the molecular mechanisms behind this association remain unclear. Using the Mendelian randomization (MR) framework, we aimed to investigate the mediating effects of putative biomarkers and other CRC risk factors in the association between BMI and CRC., Methods: We selected as mediators biomarkers of established cancer-related mechanisms and other CRC risk factors for which a plausible association with obesity exists, such as inflammatory biomarkers, glucose homeostasis traits, lipids, adipokines, insulin-like growth factor 1 (IGF1), sex hormones, 25-hydroxy-vitamin D, smoking, physical activity (PA) and alcohol consumption. We used inverse-variance weighted MR in the main univariable analyses and performed sensitivity analyses (weighted-median, MR-Egger, Contamination Mixture). We used multivariable MR for the mediation analyses., Results: Genetically predicted BMI was positively associated with CRC risk [odds ratio per SD (5 kg/m2) = 1.17, 95% CI: 1.08-1.24, P-value = 1.4 × 10-5] and robustly associated with nearly all potential mediators. Genetically predicted IGF1, fasting insulin, low-density lipoprotein cholesterol, smoking, PA and alcohol were associated with CRC risk. Evidence for attenuation was found for IGF1 [explained 7% (95% CI: 2-13%) of the association], smoking (31%, 4-57%) and PA (7%, 2-11%). There was little evidence for pleiotropy, although smoking was bidirectionally associated with BMI and instruments were weak for PA., Conclusions: The effect of BMI on CRC risk is possibly partly mediated through plasma IGF1, whereas the attenuation of the BMI-CRC association by smoking and PA may reflect confounding and shared underlying mechanisms rather than mediation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Importance: Prenatal experiences can influence fetal brain development., Objective: To examine associations of maternal prenatal body mass index (BMI) with cognition and behavior of offspring born full-term., Design, Setting, and Participants: This cohort study examined follow-up data from a breastfeeding promotion intervention at 31 hospitals and affiliated polyclinics in the Republic of Belarus. Participants included 11 276 children who were evaluated from birth (1996-1997) to adolescence (2017-2019), with maternal BMI information available in prenatal medical records., Exposures: Maternal BMI, calculated as weight in kilograms divided by height in meters squared, after 35 weeks gestation; secondary analyses examined maternal BMI at other time points and paternal BMI., Main Outcomes and Measures: Trained pediatricians assessed child cognition with the Wechsler Abbreviated Scales of Intelligence (WASI) at 6.5 years and the computerized self-administered NeuroTrax battery at 16 years, both with an approximate mean (SD) of 100 (15). Parents and teachers rated behaviors at 6.5 years using the Strengths and Difficulties Questionnaire (SDQ, range 0-40). Mixed-effects linear regression analyses corrected for clustering, adjusted for the randomized intervention group and baseline parental sociodemographic characteristics, and were considered mediation by child BMI., Results: Among 11 276 participants, 9355 women (83%) were aged 20 to 34 years, 10 128 (89.8%) were married, and 11 050 (98.0%) did not smoke during pregnancy. Each 5-unit increase in of maternal late-pregnancy BMI (mean [SD], 27.2 [3.8]) was associated with lower offspring WASI performance intelligence quotient (IQ) (-0.52 points; 95% CI, -0.87 to -0.17 points) at 6.5 years and lower scores on 5 of 7 NeuroTrax subscales and the global cognitive score at 16 years (-0.67 points; 95% CI, -1.06 to -0.29 points). Results were similar after adjustment for sociodemographic characteristics, pregnancy complications, and paternal BMI and were not mediated by child weight. Higher late pregnancy maternal BMI was also associated with more behavioral problems reported on the SDQ by teachers but not associated with parent-reported behaviors (externalizing behaviors: 0.13 points; 95% CI, 0.02 to 0.24 points; and total difficulties: 0.14 points, 95% CI, -0.02 to 0.30 points). Results were similar for maternal BMI measured in the first trimester or postpartum. In contrast, higher 6.5-year paternal BMI was associated with slightly better child cognition (WASI verbal IQ: 0.42 points; 95% CI, 0.02 to 0.82 points; NeuroTrax executive function score: 0.68 points; 95% CI, 0.24 to 1.12 points) and fewer teacher-reported behavioral problems (total difficulties: -0.29 points; 95% CI, -0.46 to -0.11 points)., Conclusions and Relevance: This cohort study supports findings from animal experiments and human observational studies in settings with higher maternal BMI and obesity rates. Higher maternal prenatal BMI may be associated with poorer offspring brain development, although residual confounding cannot be excluded.

Objective: The aim of this study was to investigate the relationship of BMI with subsequent statural growth among children born in the era of the obesity epidemic., Methods: Among 18,271 children from Belarus (n = 16,781, born 1996 to 1997) and the United States (n = 1,490, born 1999 to 2002), multivariable linear and ordinal logistic regression was used to analyze associations of BMI z score from infancy to adolescence with subsequent standardized length and height velocity, standing height and its components (trunk and leg lengths), and pubertal timing., Results: The prevalence of early adolescent obesity was 6.2% in Belarus and 12.8% in the United States. In both Belarusian and US children, higher BMI z scores in infancy and childhood were associated with faster length and height velocity in early life, while higher BMI z scores during middle childhood were associated with slower length and height velocity during adolescence. Associations with greater standing height and trunk length and earlier pubertal development in adolescence were stronger for BMI z scores at middle childhood than BMI z scores at birth or infancy., Conclusions: These findings in both Belarus and the United States support the role of higher BMI in accelerating linear growth in early life (taller stature and longer trunk length) but earlier pubertal development and slower linear growth during adolescence., (© 2019 The Obesity Society.)

Background: High body mass index (BMI) is associated with mortality, but the pervasive problem of confounding and reverse causality in observational studies limits inference about the direction and magnitude of causal effects. We aimed to obtain estimates of the causal association of BMI with all-cause and cause-specific mortality., Methods and Findings: In a record-linked, intergenerational prospective study from the general population of Sweden, we used two-sample instrumental variable (IV) analysis with data from 996,898 fathers (282,407 deaths) and 1,013,083 mothers (153,043 deaths) and their sons followed up from January 1, 1961, until December 31, 2004. Sons' BMI was used as the instrument for parents' BMI to compute hazard ratios (HRs) for risk of mortality per standard deviation (SD) higher parents' BMI. Using offspring exposure as an instrument for parents' exposure is unlikely to be affected by reverse causality (an important source of bias in this context) and reduces confounding. IV analyses supported causal associations between higher BMI and greater risk of all-cause mortality (HR [95% confidence interval (CI)] per SD higher fathers' BMI: 1.29 [1.26-1.31] and mothers' BMI: 1.39 [1.35-1.42]) and overall cancer mortality (HR per SD higher fathers' BMI: 1.20 [1.16-1.24] and mothers' BMI: 1.29 [1.24-1.34]), including 9 site-specific cancers in men (bladder, colorectum, gallbladder, kidney, liver, lung, lymphatic system, pancreas, and stomach) and 11 site-specific cancers in women (gallbladder, kidney, liver, lung, lymphatic system, ovaries, pancreas, stomach, uterus, cervix, and endometrium). There was evidence supporting causal associations between higher BMI in mothers and greater risk of mortality from kidney disease (HR: 2.17 [1.68-2.81]) and lower risk of mortality from suicide (HR: 0.77 [0.65-0.90]). In both sexes, there was evidence supporting causal associations between higher BMI and mortality from cardiovascular diseases (CVDs), stroke, diabetes, and respiratory diseases. We were unable to test the association between sons' and mothers' BMIs (as mothers' data were unavailable) or whether the instrument was independent of unmeasured or residual confounding; however, the associations between parents' mortality and sons' BMI were negligibly influenced by adjustment for available confounders., Conclusions: Consistent with previous large-scale meta-analyses and reviews, results supported the causal role of higher BMI in increasing the risk of several common causes of death, including cancers with increasing global incidence. We also found positive effects of BMI on mortality from respiratory disease, prostate cancer, and lung cancer, which has been inconsistently reported in the literature, suggesting that the causal role of higher BMI in mortality from these diseases may be underestimated. Furthermore, we expect different patterns of bias in the current observational and IV analyses; therefore, the similarities between our findings from both methods increases confidence in the results. These findings support efforts to understand the mechanisms underpinning these effects to inform targeted interventions and develop population-based strategies to reduce rising obesity levels for disease prevention., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: GDS is a member of the Editorial Board of PLOS Medicine. All other authors have declared that no competing interests exist.

Importance: The American Academy of Pediatrics currently recommends weight for length (WFL) for assessment of weight status in children younger than 2 years but body mass index (BMI) for children older than 2 years. However, the clinical implications of using WFL vs BMI in children younger than 2 years as an indicator of future health outcomes remains understudied., Objective: To compare associations of overweight based on WFL vs BMI in children younger than 2 years with cardiometabolic outcomes during early adolescence., Design, Setting, and Participants: This prospective study of birth cohorts in the United States (Project Viva) and Belarus (Promotion of Breastfeeding Intervention Trial [PROBIT]) performed from June 1, 1996, to November 31, 2002, included 13 666 children younger than 2 years., Main Exposures: Overweight defined as Centers for Disease Control and Prevention (CDC) WFL in the 95th percentile or greater, World Health Organization (WHO) WFL in the 97.7th percentile or greater, or WHO BMI in the 97.7th percentile or greater at 6, 12, 18, or 24 months of age., Main Outcomes and Measures: Primary outcomes were fat mass index, insulin resistance, metabolic risk score, and obesity during early adolescence. Secondary outcomes were height and BMI z scores, sum of skinfolds, waist circumference, and systolic blood pressure during early adolescence., Results: The study included 919 children (mean [SD] age, 12.9 [0.9] years; 460 [50.1%] male; and 598 [65.1%] white) from Project Viva and 12 747 children (mean [SD] age, 11.5 [0.5] years; 6204 [48.7%] male; and 12 747 [100%] white) from PROBIT. During 6 to 24 months of age, in Project Viva, 206 children (22.4%) were overweight at any of the 4 times points according to the CDC WFL, 160 (17.4%) according to WHO WFL, and 161 (17.5%) according to WHO BMI cut points. In PROBIT, 3715 children (29.1%) were overweight at any of the 4 time points according to the CDC WFL, 3069 (24.1%) according to WHO WFL, and 3125 (24.5%) according to WHO BMI cut points. After maternal and child characteristics were adjusted for, being ever overweight (vs never overweight) during 6 to 24 months of age was associated with higher likelihood of adverse cardiometabolic risk markers during early adolescence, but associations did not differ substantially across WFL and BMI cut points in either cohort. For example, for fat mass index in Project Viva, β = 0.9 (95% CI, 0.5-1.4) for the CDC WFL, β = 1.1 (95% CI, 0.6-1.6) for WHO WFL, and β = 1.4 (95% CI, 0.9-1.9) for WHO BMI. For PROBIT, β = 0.5 (95% CI, 0.4-0.6) for the CDC WFL, β = 0.6 (95% CI, 0.5-0.7) for WHO WFL, and β = 0.6 (95% CI, 0.5-0.6) for WHO BMI. Neither growth metric in infancy was superior over the others based on F statistics (Project Viva: 17.1-17.8; PROBIT: 87.1-88.7). Findings were similar for insulin resistance, metabolic risk score, obesity, and secondary outcomes., Conclusions and Relevance: Choice of WFL vs BMI to define overweight during the first 2 years of life may not greatly affect the association with cardiometabolic outcomes during early adolescence. The findings appear to have important implications for investigators seeking to use BMI as a growth metric for epidemiologic research and for practitioners monitoring the weight status of children younger than 2 years.

Objective: To examine associations of parental socioeconomic position with early-life offspring body mass index (BMI) trajectories in a middle-income country., Subjects: Overall, 12,385 Belarusian children born 1996-97 and enrolled in a randomised breastfeeding promotion trial at birth, with 3-14 measurements of BMI from birth to 7 years., Methods: Cohort analysis in which exposures were parental education (common secondary or less; advanced secondary or partial university; completed university) and occupation (manual; non-manual) at birth, and the outcome was BMI z-score trajectories estimated using multilevel linear spline models, controlling for trial arm, location, parental BMI, maternal smoking status and number of older siblings., Results: Infants born to university-educated mothers were heavier at birth than those born to secondary school-educated mothers [by 0.13 BMI z-score units (95% confidence interval, CI: 0.07, 0.19) for girls and 0.11 (95% CI: 0.05, 0.17) for boys; equivalent for an infant of average birth length to 43 and 38 g, respectively]. Between the ages of 3-7 years children of the most educated mothers had larger BMI increases than children of the least educated mothers. At age 7 years, after controlling for trial arm and location,  children of university-educated mothers had higher BMIs than those born to secondary school-educated mothers by 0.11 z-score (95% CI: 0.03, 0.19) among girls and 0.18 (95% CI: 0.1, 0.27) among boys, equivalent to differences in BMI for a child of average height of 0.19 and 0.26 kg/m 2 , respectively. After further controlling for parental BMI, these differences attenuated to 0.08 z-score (95% CI: 0, 0.16) and 0.16 z-score (95% CI: 0.07, 0.24), respectively, but changed very little after additional adjustment for number of older siblings and mother's smoking status. Associations were similar when based on paternal educational attainment and highest household occupation., Conclusions: In Belarus, consistent with some middle-income countries, higher socioeconomic position was associated with greater BMI trajectories from age 3 onwards.

Background: Epidemiological studies suggest a potential role for obesity and determinants of adult stature in prostate cancer risk and mortality, but the relationships described in the literature are complex. To address uncertainty over the causal nature of previous observational findings, we investigated associations of height- and adiposity-related genetic variants with prostate cancer risk and mortality., Methods: We conducted a case-control study based on 20,848 prostate cancers and 20,214 controls of European ancestry from 22 studies in the PRACTICAL consortium. We constructed genetic risk scores that summed each man's number of height and BMI increasing alleles across multiple single nucleotide polymorphisms robustly associated with each phenotype from published genome-wide association studies., Results: The genetic risk scores explained 6.31 and 1.46% of the variability in height and BMI, respectively. There was only weak evidence that genetic variants previously associated with increased BMI were associated with a lower prostate cancer risk (odds ratio per standard deviation increase in BMI genetic score 0.98; 95% CI 0.96, 1.00; p = 0.07). Genetic variants associated with increased height were not associated with prostate cancer incidence (OR 0.99; 95% CI 0.97, 1.01; p = 0.23), but were associated with an increase (OR 1.13; 95 % CI 1.08, 1.20) in prostate cancer mortality among low-grade disease (p heterogeneity, low vs. high grade <0.001). Genetic variants associated with increased BMI were associated with an increase (OR 1.08; 95 % CI 1.03, 1.14) in all-cause mortality among men with low-grade disease (p heterogeneity = 0.03)., Conclusions: We found little evidence of a substantial effect of genetically elevated height or BMI on prostate cancer risk, suggesting that previously reported observational associations may reflect common environmental determinants of height or BMI and prostate cancer risk. Genetically elevated height and BMI were associated with increased mortality (prostate cancer-specific and all-cause, respectively) in men with low-grade disease, a potentially informative but novel finding that requires replication.

Objective: To investigate the associations of body mass index (BMI) and grip strength with objective measures of physical performance (chair rise time, walking speed and balance) including an assessment of sex differences and non-linearity., Methods: Cross-sectional data from eight UK cohort studies (total N = 16,444) participating in the Healthy Ageing across the Life Course (HALCyon) research programme, ranging in age from 50 to 90+ years at the time of physical capability assessment, were used. Regression models were fitted within each study and meta-analysis methods used to pool regression coefficients across studies and to assess the extent of heterogeneity between studies., Results: Higher BMI was associated with poorer performance on chair rise (N = 10,773), walking speed (N = 9,761) and standing balance (N = 13,921) tests. Higher BMI was associated with stronger grip strength in men only. Stronger grip strength was associated with better performance on all tests with a tendency for the associations to be stronger in women than men; for example, walking speed was higher by 0.43 cm/s (0.14, 0.71) more per kg in women than men. Both BMI and grip strength remained independently related with performance after mutual adjustment, but there was no evidence of effect modification. Both BMI and grip strength exhibited non-linear relations with performance; those in the lowest fifth of grip strength and highest fifth of BMI having particularly poor performance. Findings were similar when waist circumference was examined in place of BMI., Conclusion: Older men and women with weak muscle strength and high BMI have considerably poorer performance than others and associations were observed even in the youngest cohort (age 53). Although causality cannot be inferred from observational cross-sectional studies, our findings suggest the likely benefit of early assessment and interventions to reduce fat mass and improve muscle strength in the prevention of future functional limitations.

Background: Measures of regional adiposity have been proposed as alternatives to the measurement of body mass index (BMI) for identifying persons at risk of future disease., Objective: The objective was to compare the magnitudes of association of BMI and alternative measurements of adiposity with coronary heart disease, diabetes, and cardiovascular disease risk factors and all-cause mortality., Design: Data from 4 cohorts of adults [3937 women from the British Women's Heart and Health Study (BWHHS); 2367 and 1950 men from phases 1 and 3, respectively, of the Caerphilly Prospective Study (CaPS); 403 men and women from the Boyd Orr Study; and 789 men and women from the Maidstone-Dewsbury Study] were analyzed., Results: The magnitudes of associations of BMI with incident coronary heart disease and cardiovascular disease risk factors were similar to those with measurements of central adiposity [waist circumference (WC), waist-hip ratio (WHR), or waist-height ratio (WHtR)] and more direct measurements of fat mass (bioimpedance/skinfold thickness). In CaPS (men only), there was no strong evidence of differences in the strengths of association with incident diabetes between BMI, WC, WHR, and WHtR (P for heterogeneity > 0.49 for all). In the BWHHS (women only), there was statistical evidence that WC [hazard ratio (HR): 2.35; 95% CI: 2.03, 2.73] and WHtR (HR: 2.29; 95% CI: 1.98, 2.66) were more strongly associated with diabetes than with BMI (HR: 1.80; 95% CI: 1.59, 2.04) (P for heterogeneity < 0.02 for both). Central adiposity measurements were positively associated with all-cause mortality, as was BMI, but only when those with a BMI (in kg/m(2)) <22.5 were removed from the analyses., Conclusion: No strong evidence supports replacing BMI in clinical or public health practice with other adiposity measures.

Background: Previous studies reported inconsistent associations between breastfeeding and body mass index (BMI; in kg/m2). Associations with body fatness are unknown., Objective: We investigated the association of breastfeeding with fatness measured by dual-energy X-ray absorptiometry., Design: The prospective cohort study involved 4325 singletons with measurements at 9-10 y of age to assess the main outcomes of BMI and total and trunk fat masses., Results: Prevalence of any breastfeeding was 82%. In crude analyses, breastfeeding was inversely associated with total fat mass [% change per category increase (4 categories)] in breastfeeding duration (-4.4%; 95% CI: -3.1%, -5.6%) and trunk fat mass (-0.5%; 95% CI: -1.1%, 0.1%); the odds of adiposity were measured by total [odds ratio (OR): 0.81; 95% CI: 0.75, 0.88] and trunk (OR: 0.78; 95% CI: 0.71, 0.84) fat masses in the top decile. In adjusted models, the inverse association of breastfeeding with mean total fat mass was attenuated by 59% (% change per category increase in breastfeeding duration: -1.8%; 95% CI: -0.5%, -3.1%), but associations with trunk fat mass (% change per category increase in breastfeeding duration: -0.6%; 95% CI: 0.0%, -1.3%) and the ORs for total (0.76; 95% CI: 0.69, 0.84) and trunk (0.74; 95% CI: 0.67, 0.81) fat masses in the top decile were little altered. Children breastfed >or=6 mo had the lowest odds of total fat mass in the top decile (OR: 0.45; 95% CI: 0.33, 0.62). In multivariate models, there was little evidence that breastfeeding was associated with mean or threshold values of BMI., Conclusions: The protective association of breastfeeding with mean total fat mass was attenuated somewhat after adjustment for confounders, which indicated that confounding may explain this association. Breastfeeding may protect against obesity if maintained for >or=6 mo.

Background: It is unclear whether early life body mass index (BMI; in kg/m(2)) is associated with adult cardiovascular disease., Objective: The objective was to assess the association of early life BMI with the risk of ischemic heart disease (IHD) and stroke., Design: The association between early life BMI and risk of adult mortality from IHD and stroke was assessed in 3 historical cohort studies in which height and weight had been assessed by using standard procedures. Participants were traced and linked to national mortality data. Participants in the 3 cohorts were born between 1922 and 1937, 1927 and 1956, and 1928 and 1950 and were aged 2-15, 9-18, and 16-22 y, respectively, at the time of assessment of their height and weight., Results: Participants in all 3 cohorts had mean BMIs similar to those reported for contemporary children and young adults, but fewer of the cohort participants were overweight or obese. BMI was not associated with future risk of IHD or stroke in any cohort. The pooled (all 3 cohorts) adjusted hazard ratio per SD of early life BMI was 1.09 (95% CI: 1.01, 1.19) for IHD and 0.94 (95% CI: 0.82, 1.08) for stroke. The pooled hazard ratio of IHD when participants who were overweight or obese for their age were compared with all other participants was 1.34 (95% CI: 0.95, 1.91), and no association was found between overweight or obesity and stroke risk. The effects of BMI did not vary by cohort or by age., Conclusion: These results do not provide strong evidence that being overweight or obese in childhood is associated with future cardiovascular disease risk.

Background: Evidence from observational studies has suggested that breastfeeding may reduce the prevalence of obesity in later life., Objective: The objective was to examine whether initial breastfeeding is related to lower mean body mass index (BMI; in kg/m(2)) throughout life., Design: The study was a systematic review of published studies investigating the association between infant feeding and a measure of obesity or adiposity in later life, which was supplemented with data from unpublished sources. Analyses were based on the mean differences in BMI between those subjects who were initially breastfed and those who were formula-fed (expressed as breastfed minus bottle-fed), which were pooled by using fixed-effects models throughout., Results: From 70 eligible studies, 36 mean differences in BMI (from 355 301 subjects) between those breastfed and those formula-fed (reported as exclusive feeding in 20 studies) were obtained. Breastfeeding was associated with a slightly lower mean BMI than was formula feeding (-0.04; 95% CI: -0.05, -0.02). The mean difference in BMIs appeared larger in 15 small studies of <1000 subjects (-0.19; 95% CI: -0.31, -0.08) and smaller in larger studies of >or=1000 subjects (-0.03; 95% CI: -0.05, -0.02). An Egger test was statistically significant (P = 0.002). Adjustment for socioeconomic status, maternal smoking in pregnancy, and maternal BMI in 11 studies abolished the effect (-0.10; 95% CI: -0.14, -0.06 before adjustment; -0.01; 95% CI: -0.05, 0.03 after adjustment)., Conclusions: Mean BMI is lower among breastfed subjects. However, the difference is small and is likely to be strongly influenced by publication bias and confounding factors. Promotion of breastfeeding, although important for other reasons, is not likely to reduce mean BMI.

Associations between childhood BMI and adult cancer risk were investigated in a historical cohort study based on the Carnegie ("Boyd Orr") Survey of Diet and Health in Pre-War Britain (1937-9). In 14 centres in England and Scotland, children had their height and weight measured. We included 2,347 individuals aged between 2 and 14 years 9 months at the time of measurement, who were traced through the National Health Service Central Register. Relative cancer risk (registration or death) was estimated in relation to age- and sex-specific BMI SD scores. We studied associations with (i) all cancers, (ii) cancer groups stratified according to their relationship to smoking and (iii) certain site-specific cancers. In the 50 years of follow-up, 188 men and 192 women developed cancer. There was a 9% increase (95% CI -3 to 22%) in risk of cancer in adulthood per SD increase in BMI measured in childhood. There was no evidence of confounding by childhood or adulthood socioeconomic position, other anthropometric variables, childhood energy intake or birth order. There was a 30% increase (95% CI 10-54%) in risk of smoking-related cancers per SD increase in childhood BMI. There was no relationship between BMI and cancers not related to smoking. Associations for all cancers and non-smoking-related cancers tended to be stronger in children who were measured at an older (>8 years) rather than a younger (< or =8 years) age. We conclude that childhood BMI is related to increased risk of cancer in later life, particularly smoking-related cancers., (Copyright 2004 Wiley-Liss, Inc.)

BackgroundAssessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer.Methods and findingsWe identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m2]), but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79-1.08]) (Pheterogeneity = 4.3x10-3). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results.ConclusionsOur results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior.

Body mass index (BMI) is inversely associated with lung cancer risk in observational studies, even though it increases the risk of several other cancers, which could indicate confounding by tobacco smoking or reverse causality. We used the two-sample Mendelian randomization (MR) approach to circumvent these limitations of observational epidemiology by constructing a genetic instrument for BMI, based on results from the GIANT consortium, which was evaluated in relation to lung cancer risk using GWAS results on 16,572 lung cancer cases and 21,480 controls. Results were stratified by histological subtype, smoking status and sex. An increase of one standard deviation (SD) in BMI (4.65 Kg/m(2)) raised the risk for lung cancer overall (OR = 1.13; P = 0.10). This was driven by associations with squamous cell (SQ) carcinoma (OR = 1.45; P = 1.2 × 10(-3)) and small cell (SC) carcinoma (OR = 1.81; P = 0.01). An inverse trend was seen for adenocarcinoma (AD) (OR = 0.82; P = 0.06). In stratified analyses, a 1 SD increase in BMI was inversely associated with overall lung cancer in never smokers (OR = 0.50; P = 0.02). These results indicate that higher BMI may increase the risk of certain types of lung cancer, in particular SQ and SC carcinoma.

Background: The associations of adiposity with aggressive prostate cancer risk are unclear. Using two‐sample Mendelian randomization, we assessed the association of metabolically unfavourable adiposity (UFA), favourable adiposity (FA) and for comparison body mass index (BMI), with prostate cancer, including aggressive prostate cancer. Methods: We examined the association of these genetically predicted adiposity‐related traits with risk of prostate cancer overall, aggressive and early onset disease using outcome summary statistics from the PRACTICAL consortium (including 15,167 aggressive cases). Results: In inverse‐variance weighted models, there was little evidence that genetically predicted one standard deviation higher UFA, FA and BMI were associated with aggressive prostate cancer [OR: 0.85 (95% CI:0.61–1.19), 0.80 (0.53–1.23) and 0.97 (0.88–1.08), respectively]; these associations were largely consistent in sensitivity analyses accounting for horizontal pleiotropy. There was no strong evidence that genetically determined UFA, FA or BMI were associated with overall prostate cancer or early age of onset prostate cancer. Conclusions: We did not find differences in the associations of UFA and FA with prostate cancer risk, which suggest that adiposity is unlikely to influence prostate cancer via the metabolic factors assessed; however, these did not cover some aspects related to metabolic health that may link obesity with aggressive prostate cancer, which should be explored in future studies. [ABSTRACT FROM AUTHOR]

Summary: Background: Caesarean delivery has been associated with later adiposity, perhaps via early programming or perhaps because of residual confounding by maternal or birth characteristics. Objectives: Examine associations of caesarean delivery with adiposity and cardio‐metabolic biomarkers. Methods: Observational analysis of 15 069 children in the PROBIT cohort in Belarus. We examined measures of child anthropometry and blood pressure at 6.5, 11.5 and 16 years and fasting blood (11.5 years). Results: Caesarean‐delivered children were slightly heavier at 6.5 (mean BMI 15.8 vs. 15.6 kg/m2), 11.5 (18.4 vs. 18.2) and 16 years (21.5 vs. 21.3). After adjustment for prenatal characteristics including maternal third trimester BMI, however, we observed no association of caesarean versus vaginal delivery with child BMI (β 0.05 kg/m2; 95%CI: −0.03, 0.14), sum of skinfolds (0.14 mm; −0.13, 0.42), waist circumference (−0.07 cm; −0.23, 0.10), obesity (OR 0.99; 0.76, 1.29), or systolic (−0.20 mmHg; −0.70, 0.30) or diastolic (−0.17 mmHg, −0.60, 0.26) blood pressure at 6.5 years; results were similar at 11.5 and 16 years. At 11.5 years, we observed a modest association of caesarean delivery with fasting insulin (0.33 mU/L; 0.00, 0.65). Conclusions: Caesarean delivery had little or no association with adiposity or related cardio‐metabolic biomarkers in childhood. Adjustment for maternal BMI attenuated all outcome effect estimates. [ABSTRACT FROM AUTHOR]

The evidence that fetal life and early infancy are "critical" or "sensitive" ages for later development of cardiometabolic disease is based on flawed methods for comparing different age periods. Moreover, most previous studies have limited their focus to weight gain, rather than growth in length/height or body mass index (weight (kg)/height (m)2). We undertook a secondary analysis of data from the Promotion of Breastfeeding Intervention Trial (1996–2010), a birth cohort study nested within a large cluster-randomized trial in the Republic of Belarus, that had repeated measurements of weight and length/height taken from birth to 11.5 years of age. We used mixed-effects linear models to analyze associations of changes in standardized weight, length/height, and body mass index during 5 age periods (conception to birth, birth to age 3 months, ages 3–12 months, ages 12 months–6.5 years, and ages 6.5–11.5 years) with fasting glucose, insulin, insulin resistance, β-cell function, and adiponectin at age 11.5 years. We observed strong associations between the metabolic markers and all 3 growth measures, with the largest magnitudes being observed during the latest age period (ages 6.5–11.5 years) and negligible associations during gestation and the first year of life. Later age periods appear more "sensitive" than earlier periods to the adverse metabolic association with rapid growth in childhood. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is the second most common male cancer worldwide, but there is substantial geographical variation, suggesting a potential role for modifiable risk factors in prostate carcinogenesis.Methods: We identified previously reported prostate cancer risk factors from the World Cancer Research Fund (WCRF)'s systematic appraisal of the global evidence (2018). We assessed whether each identified risk factor was causally associated with risk of overall (79 148 cases and 61 106 controls) or aggressive (15 167 cases and 58 308 controls) prostate cancer using Mendelian randomization (MR) based on genome-wide association-study summary statistics from the PRACTICAL and GAME-ON/ELLIPSE consortia. We assessed evidence for replication in UK Biobank (7844 prostate-cancer cases and 204 001 controls).Results: WCRF identified 57 potential risk factors, of which 22 could be instrumented for MR analyses using single nucleotide polymorphisms. For overall prostate cancer, we identified evidence compatible with causality for the following risk factors (odds ratio [OR] per standard deviation increase; 95% confidence interval): accelerometer-measured physical activity, OR = 0.49 (0.33-0.72; P = 0.0003); serum iron, OR = 0.92 (0.86-0.98; P = 0.007); body mass index (BMI), OR = 0.90 (0.84-0.97; P = 0.003); and monounsaturated fat, OR = 1.11 (1.02-1.20; P = 0.02). Findings in our replication analyses in UK Biobank were compatible with our main analyses (albeit with wide confidence intervals). In MR analysis, height was positively associated with aggressive-prostate-cancer risk: OR = 1.07 (1.01-1.15; P = 0.03).Conclusions: The results for physical activity, serum iron, BMI, monounsaturated fat and height are compatible with causality for prostate cancer. The results suggest that interventions aimed at increasing physical activity may reduce prostate-cancer risk, although interventions to change other risk factors may have negative consequences on other diseases. [ABSTRACT FROM AUTHOR]

Background: The workplace environment potentially provides access to a large population who are employed, and it is an employer's responsibility to provide appropriate conditions for its employees. Whilst the aetiology of cardiovascular disease is multifactorial, it is generally acknowledged that working conditions, gender and age are involved in its development. Male-dominated industries (comprising > 70% male workers, e.g., agriculture, construction, manufacturing, mining, transport and technology) have a higher prevalence of health risk behaviours than other population subgroups. Working in a gender-dominated industry can impact an employee's health and wellbeing, particularly for the opposite sex. This systematic review examines workplace interventions that address the health and wellbeing of employees in male-dominated industries. Methods: We will include randomised controlled trials and studies with non-randomised intervention groups. The interventions must aim to improve employee physical and/or mental health and wellbeing implemented in the workplace in male-dominated industries. There will be no limits on date. The following electronic databases will be searched for published studies: Web of Science, Embed, MedLine, PsycInfo and the Cochrane Database. The search strategy will include free-text terms and MeSH vocabulary, including 'male-dominated industries', 'workplace interventions', 'occupational stress', 'mental health', 'cardiovascular disease', 'blood pressure', 'body mass index' and 'exercise'. Two authors will independently select, review and extract data from studies that meet the inclusion criteria. The Cochrane's Risk of Bias tool will be used to assess risk of bias. We will perform structured summaries of the included studies and, if possible, conduct meta-analyses or construct an Albatross plot. Discussion: There are an increasing number of interventions designed to improve employee health and wellbeing in the workplace, but no prior review that systematically evaluates their effectiveness. A systematic review is required to prioritise the future implementation of those interventions found to be most effective. Systematic review registration: PROSPERO CRD42019161283 [ABSTRACT FROM AUTHOR]

Objective: The Children's Eating Attitudes Test (ChEAT) is a self‐report questionnaire that is conventionally summarized with a single score to identify "problematic" eating attitudes, masking informative variability in different eating attitude domains. This study evaluated the empirical support for single‐ versus multifactor models of the ChEAT. For validation, we compared how well the single‐ versus multifactor‐based scores predicted body mass index (BMI). Method: Using data from 13,674 participants of the 11.5 year‐follow‐up of the Promotion of Breastfeeding Intervention Trial (PROBIT) in the Republic of Belarus, we conducted confirmatory factor analysis to evaluate the performance of 3‐ and 5‐factor models, which were based on past studies, to a single‐factor model representing the conventional summary of the ChEAT. We used cross‐validated linear regression models and the reduction in mean squared error (MSE) to compare the prediction of BMI at 11.5 and 16 years by the conventional and confirmed factor‐based ChEAT scores. Results: The 5‐factor model, based on 14 of the original 26 ChEAT items, had good fit to the data whereas the 3‐ and single‐factor models did not. The MSE for concurrent (11.5 years) BMI regressed on the 5‐factor ChEAT summary was 35% lower than that of the single‐score models, which reduced the MSE from the null model by only 1%–5%. The MSE for BMI at 16 years was 20% lower. Discussion: We found that a parsimonious 5‐factor model of the ChEAT explained the data collected from healthy Belarusian children better than the conventional summary score and thus provides a more discriminating measure of eating attitudes. [ABSTRACT FROM AUTHOR]

Background: There are observational data suggesting an inverse association between circulating concentrations of sex hormone binding globulin (SHBG) and risk of postmenopausal breast cancer. However, causality is uncertain and few studies have investigated this association by tumour receptor status. We aimed to investigate these associations under the causal framework of Mendelian randomization (MR).Methods: We used summary association estimates extracted from published genome-wide association study (GWAS) meta-analyses for SHBG and breast cancer, to perform two-sample MR analyses. Summary statistics were available for 122 977 overall breast cancer cases, of which 69 501 were estrogen receptor positive (ER+ve) and 21 468 were ER-ve, and 105 974 controls. To control for potential horizontal pleiotropy acting via body mass index (BMI), we performed multivariable inverse-variance weighted (IVW) MR as the main analysis, with the robustness of this approach further tested in sensitivity analyses.Results: The multivariable IVW MR analysis indicated a lower risk of overall (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.90, 0.98; P: 0.006) and ER+ve (OR: 0.92; 95% CI: 0.87, 0.97; P: 0.003) breast cancer, and a higher risk of ER-ve disease (OR: 1.09; 95% CI: 1.00, 1.18; P: 0.047) per 25 nmol/L higher SHBG levels. Sensitivity analyses were consistent with the findings of the main analysis.Conclusions: We corroborated the previous literature evidence coming from observational studies for a potentially causal inverse association between SHBG concentrations and risk of ER+ve breast cancer, but our findings also suggested a potential novel positive association with ER-ve disease that warrants further investigation, given the low prior probability of being true. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies have consistently shown slower weight and length gains in infants with prolonged breastfeeding than in those who were formula-fed from birth or breastfed for a shorter duration. These studies inferred that prolonged breastfeeding causes slower growth in infancy. Objective: We compared infant growth associated with ≥12 mo of breastfeeding with a shorter duration of breastfeeding on the basis of 3 different analytic approaches to the same data from a randomized trial: intention-to-treat (ITT; "as randomized"), observational ("as fed"), and instrumental variable (IV; by using randomization as an "instrument" to achieve ≥12 mo of breastfeeding). Design: This was a cluster-randomized trial of a breastfeeding-promotion intervention. Anthropometric measurements were obtained at birth and at 1, 2, 3, 6, 9, and 12 mo. Results: The 3 analytic approaches yielded different results. The ITT approach showed more rapid growth in the first 2 mo among infants randomly assigned to the breastfeeding-promotion intervention than among control infants, with a decreasing difference over the ensuing months and nearly identical weight, length, and body mass index by 12 mo. The observational analysis showed a different trend: higher weight and length in infants who were breastfed ≥12 mo than in those who were breastfed <12 mo during the first 3 mo and no difference by 6 mo, while infants who were breastfed <12 mo showed increasingly higher weight and length from 6 to 12 mo. The IV analysis showed a temporal pattern that was similar to that seen in the ITT analysis, but with larger (and less precise) differences between infants breastfed for ≥12 compared with <12 mo. Conclusions: We observed major differences in experimental (ITT and IV) compared with observational approaches to analyzing data obtained from the same children. These approaches lead to opposite causal inferences about the relation between infant feeding and growth and underline the importance of ensuring that the postulated cause (feeding) temporally precedes its hypothesized effect (growth). [ABSTRACT FROM AUTHOR]

Purpose: The insulin-like growth factor (IGF) system is modifiable by diet and lifestyle, and has been linked to prostate cancer development and progression.Methods: We conducted a prospective cohort study of 621 men diagnosed with localized prostate cancer to investigate the associations of dietary and lifestyle changes with post-diagnosis circulating levels of IGF-I and IGFBP-3. We used analysis of covariance to estimate the associations, controlling for baseline IGF-I or IGFBP-3, respectively.Results: Mean IGF-I levels were 6.5% (95% CI -12.8, -0.3%, p = 0.04) lower in men who decreased their protein intake after diagnosis compared to men who did not change. Men who changed their fruit and vegetable intake had lower IGF-I levels compared to non-changers [Decreased intake: -10.1%, 95% CI -18.4, -1.8%, p = 0.02; Increased intake: -12.0%, 95% CI -18.4, -1.8%, p = 0.002]. IGFBP-3 was 14.6% (95% CI -24.5, -4.8%, p = 0.004) lower in men who achieved a healthy body mass index after diagnosis. Men who became inactive had 9.5% higher average IGF-I levels (95% CI 0.1, 18.9%, p = 0.05).Conclusions: Decreased protein intake and body mass index, and increased physical activity and fruit and vegetable intake, following a prostate cancer diagnosis were associated with reduced post-diagnosis serum IGF-I and IGFBP-3. Counterintuitively, reduced fruit and vegetable intake was also associated with reduced IGF-I, but with weak statistical support, possibly implicating chance. If confirmed in other studies, our findings may inform potential lifestyle interventions in prostate cancer. ProtecT was registered at International Standard Randomised Controlled Trial Registry, http://isrctn.org as ISRCTN20141297. [ABSTRACT FROM AUTHOR]

Background: Clinically diagnosed eating disorders may have adverse cardiometabolic consequences, including overweight or obesity and high blood pressure. However, the link between problematic eating attitudes in early adolescence, which can lead to disordered eating behaviors, and future cardiometabolic health is, to our knowledge, unknown. Objective: We assessed whether variations in midchildhood eating attitudes influence the future development of overweight or obesity and high blood pressure. Design: Of 17,046 children who participated in the Promotion of Breastfeeding Intervention Trial (PROBIT), we included 13,557 participants (79.5% response rate) who completed the Children's Eating Attitudes Test (ChEAT) at age 11.5 y and in whom we measured adiposity and blood pressure at ages 6.5, 11.5, and 16 y. We assessed whether ChEAT scores ≥85th percentile (indicative of problematic eating attitudes) compared with scores ≥85th percentile at age 11.5 y were associated with new-onset overweight, obesity, high systolic blood pressure, or high diastolic blood pressure between midchildhood and early adolescence. Results: After controlling for baseline sociodemographic confounders, we observed positive associations of problematic eating attitudes at age 11.5 y with new-onset obesity (OR: 2.18; 95% CI: 1.58, 3.02), newonset high systolic blood pressure (OR: 1.34; 95% CI: 1.05, 1.70), and new-onset high diastolic blood pressure (OR: 1.25; 95% CI: 0.99, 1.58) at age 16 y. After further controlling for body mass index at age 6.5 y, problematic eating attitudes remained positively associated with newonset obesity (OR: 1.80; 95% CI: 1.28, 2.53); however, associations with new-onset high blood pressure were attenuated (OR: 1.14; 95% CI: 0.89, 1.45 and OR: 1.09; 95% CI: 0.86, 1.39 for new-onset systolic and diastolic blood pressure, respectively). Conclusions: Problematic eating attitudes in midchildhood seem to be related to the development of obesity in adolescence, a relatively novel observation with potentially important public health implications for obesity control. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies indicate a possible inverse relationship between prostate-specific antigen (PSA) and body mass index (BMI), and a positive relationship between PSA and age. We investigated the associations between age, BMI, PSA, and screen-detected prostate cancer to determine whether an age-BMI-adjusted PSA model would be clinically useful for detecting prostate cancer.Methods: Cross-sectional analysis nested within the UK ProtecT trial of treatments for localized cancer. Of 18,238 men aged 50-69 years, 9,457 men without screen-detected prostate cancer (controls) and 1,836 men with prostate cancer (cases) met inclusion criteria: no history of prostate cancer or diabetes; PSA < 10 ng/ml; BMI between 15 and 50 kg/m2. Multivariable linear regression models were used to investigate the relationship between log-PSA, age, and BMI in all men, controlling for prostate cancer status.Results: In the 11,293 included men, the median PSA was 1.2 ng/ml (IQR: 0.7-2.6); mean age 61.7 years (SD 4.9); and mean BMI 26.8 kg/m2 (SD 3.7). There were a 5.1% decrease in PSA per 5 kg/m2 increase in BMI (95% CI 3.4-6.8) and a 13.6% increase in PSA per 5-year increase in age (95% CI 12.0-15.1). Interaction tests showed no evidence for different associations between age, BMI, and PSA in men above and below 3.0 ng/ml (all p for interaction >0.2). The age-BMI-adjusted PSA model performed as well as an age-adjusted model based on National Institute for Health and Care Excellence (NICE) guidelines at detecting prostate cancer.Conclusions: Age and BMI were associated with small changes in PSA. An age-BMI-adjusted PSA model is no more clinically useful for detecting prostate cancer than current NICE guidelines. Future studies looking at the effect of different variables on PSA, independent of their effect on prostate cancer, may improve the discrimination of PSA for prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Previous studies of early life influences on later growth in childhood have varied in their analytical approaches, particularly with respect to 'adjustment' for differences in size at the beginning of the growth period examined.Methods: We compared three commonly used statistical models to assess the effect of maternal body mass index (BMI) on growth between 6.5 and 11.5 years in a large cohort of Belarusian children, as follows: (Model 1) analysis of the difference in anthropometric measurements between the two ages; (Model 2) analysis of the measurement at 11.5 years after adjustment for the same measurement at 6.5 years; and (Model 3) analysis of the difference in measurements after adjustment for the measurement at 6.5 years (mathematically identical to Model 2).Results: Among PROBIT children of obese mothers (BMI ≥ 30 kg/m 2 ) vs those of mothers with normal BMI (18.5 to < 25 kg/m 2 ), Model 1 yielded larger increases in most weight and adiposity outcomes than did Model 2. We show that these larger effects arise because Model 2 parameterizes the effect of maternal BMI twice in same model: once for its effect on size at 6.5 years, and a second time for its effect on growth over the 5-year period between 6.5 and 11.5 years. Similar results were obtained in analogous analyses from cohorts in Boston, MA, and Singapore.Conclusion: Analysing the effect of exposure on change in outcome between two ages (Model 1) is clearly preferable to 'adjustment' for the outcome at the earlier age whenever the exposure under study affects the outcome at the earlier age. [ABSTRACT FROM AUTHOR]

Background: Several recent "developmental origins" studies have reported increased long-term risks of adiposity, especially truncal adiposity, among children born small for gestational age (SGA). Objective: We assessed the effects of SGA birth and weight gain in early infancy on adiposity at age 11.5 y. Design: From a cluster-randomized breastfeeding promotion trial in 17,046 Belarusian children, we measured height, weight, waist and hip circumferences, triceps and subscapular skinfold thicknesses, and bioimpedance measures of percentage body fat at age 11.5 y. Children born SGA (birth weight <10th percentile) and those born large for gestational age (LGA; >90th percentile for gestational age) were compared with those born appropriate for gestational age (AGA). Weight gain from birth to 6 mo was categorized as high (>0.67-SD increase in weight-for-age), low (>0.67-SD decrease in weight-forage), or normal. Multilevel statistical models accounted for clustered measurement and controlled for maternal and paternal height and body mass index (BMI), maternal education, geographic region, urban compared with rural residence, and the child's exact age at follow-up. Results: Children born SGA had a significantly lower BMI, percentage body fat, and fat mass index than did those born AGA, with a dose-response effect across 2 subcategories of SGA (P<0.001 for all comparisons). No difference was observed in waist-to-hip ratio, although the subscapular-to-triceps skinfold ratio was slightly but significantly (P<0.001) higher in children born SGA. Differences among the study groups continued to increase since the previous follow-up at 6.5 y. SGA infants with catch-up growth in the first 3-6 mo had growth and adiposity measures intermediate between those born SGA without catch-up and those born AGA. Opposite effects of similar magnitude were observed in children born LGA. Conclusion: The 11.5-y-old Belarusian children born SGA were shorter, were thinner, and had less body fat than their non-SGA peers, irrespective of postnatal weight gain. [ABSTRACT FROM AUTHOR]

The article focuses on a randomized-controlled trial which aims to investigate effects of an intervention to promote increased duration and exclusivity of breastfeeding on child adiposity and circulating insulin-like growth factor (IGF)-I in Belarus. It mentions that the participants of this study included 17,046 breastfeeding mothers enrolled in 1996 and 1997, of whom 13,879 were followed up between January 2008 and December 2010 at a median age of 11.5 years. The main outcome measures included body mass index, percent body fat and waist circumference. The results indicated that breastfeeding has many advantages but population strategies to increase the duration and exclusivity of breastfeeding are unlikely to curb the obesity epidemic.

Background: Socio-economic differences in the prevalence of overweight/obesity may be one factor through which health inequalities arise and may vary by the population studied. Methods: Analysing a cohort of 13 889 children born in Belarus between June 1996 and December 1997, the authors investigated associations of parental educational attainment and highest household occupation with: (i) measured body mass index (BMI), waist circumference and skinfold thicknesses at age 6.5 years and (ii) the parents’ reported BMI. Results: Overall, 10% of children, 37% of mothers and 53% of fathers were either overweight or obese. Children from non-manual households were 27% [95% confidence interval (CI): 10%, 47%] more likely to be overweight/obese (based on BMI) than those from manual households. They also had larger waist circumferences and higher percentage body fat (calculated from subscapular and triceps skinfolds). Similar associations for being overweight/obese were seen for fathers [odds ratio (OR), 1.10; 95% CI: 1.02, 1.18], but mothers from non-manual households were less likely to be overweight/obese: (OR, 0.84; 95% CI: 0.79, 0. 90). Associations of childhood and parental overweight/obesity with higher educational status of either parent were similar to those observed for non-manual households. Conclusion: We observed socio-economic differentials in overweight/obesity prevalence among children and their parents in Belarus. More affluent children and their fathers were more likely to be overweight/obese but the reverse was found for mothers. [ABSTRACT FROM AUTHOR]

Observational studies suggest that obese men have a lower risk of incident prostate cancer, but an increased risk of advanced and fatal cancers. These observations could be due to confounding, detection bias, or a biological effect of obesity. Genetic studies are less susceptible to confounding than observational epidemiology and can suggest how associations between phenotypes (such as obesity) and diseases arise. To determine whether the associations between obesity and prostate cancer are causal, we conducted a genetic association study of the relationship between a single nucleotide polymorphism known to be associated with obesity (FTO rs9939609) and prostate cancer. Data are from a population-based sample of 1550 screen-detected prostate cancers, 1815 age- and general practice matched controls with unrestricted prostate specific antigen (PSA) values and 1175 low-PSA controls (PSA <0.5 ng/ml). The rs9939609 A allele, which was associated with higher BMI in the sample, was inversely associated with overall (odds ratio (OR) versus all controls = 0.93; 95% confidence interval (CI): 0.85-1.02 p = 0.12 per allele) and low-grade (OR = 0.90; 0.81-0.99 p = 0.03 per allele) prostate cancer risk, but positively associated with high-grade cancer among cases (OR high- versus low-grade cancer = 1.16; 0.99-1.37 p = 0.07 per allele). Although evidence for these effects was weak, they are consistent with observational data based on BMI phenotypes and suggest that the observed association between obesity and prostate cancer is not due to confounding. Further research should confirm these findings, extend them to other BMI-related genetic variants and determine whether they are due to detection bias or obesity-related hormonal changes. [ABSTRACT FROM AUTHOR]

Background: DNA methylation (DNAm) variation is an established predictor for several traits. In the context of oropharyngeal cancer (OPC), where 5-year survival is ~ 65%, DNA methylation may act as a prognostic biomarker. We examined the accuracy of DNA methylation biomarkers of 4 complex exposure traits (alcohol consumption, body mass index [BMI], educational attainment and smoking status) in predicting all-cause mortality in people with OPC. Results: DNAm predictors of alcohol consumption, BMI, educational attainment and smoking status were applied to 364 individuals with OPC in the Head and Neck 5000 cohort (HN5000; 19.6% of total OPC cases in the study), followed up for median 3.9 years; inter-quartile range (IQR) 3.3 to 5.2 years (time-to-event—death or censor). The proportion of phenotypic variance explained in each trait was as follows: 16.5% for alcohol consumption, 22.7% for BMI, 0.4% for educational attainment and 51.1% for smoking. We then assessed the relationship between each DNAm predictor and all-cause mortality using Cox proportional-hazard regression analysis. DNAm prediction of smoking was most consistently associated with mortality risk (hazard ratio [HR], 1.38 per standard deviation (SD) increase in smoking DNAm score; 95% confidence interval [CI] 1.04 to 1.83; P 0.025, in a model adjusted for demographic, lifestyle, health and biological variables). Finally, we examined the accuracy of each DNAm predictor of mortality. DNAm predictors explained similar levels of variance in mortality to self-reported phenotypes. Receiver operator characteristic (ROC) curves for the DNAm predictors showed a moderate discrimination of alcohol consumption (area under the curve [AUC] 0.63), BMI (AUC 0.61) and smoking (AUC 0.70) when predicting mortality. The DNAm predictor for education showed poor discrimination (AUC 0.57). Z tests comparing AUCs between self-reported phenotype ROC curves and DNAm score ROC curves did not show evidence for difference between the two (alcohol consumption P 0.41, BMI P 0.62, educational attainment P 0.49, smoking P 0.19). Conclusions: In the context of a clinical cohort of individuals with OPC, DNAm predictors for smoking, alcohol consumption, educational attainment and BMI exhibit similar predictive values for all-cause mortality compared to self-reported data. These findings may have translational utility in prognostic model development, particularly where phenotypic data are not available. [ABSTRACT FROM AUTHOR]