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Background: Questions remain about the effect on mortality of physical activity and sedentary behaviour over time. We summarized the evidence from studies that assessed exposure from multiple time points and critiqued the analytic approaches used.Methods: A search was performed on MEDLINE, Embase, Emcare, Scopus and Web of Science up to January 2021 for studies of repeatedly assessed physical activity or sedentary behaviour in relation to all-cause or cause-specific mortality. Relative risks from individual studies were extracted. Each study was assessed for risk of bias from multiple domains.Results: We identified 64 eligible studies (57 on physical activity, 6 on sedentary behaviour, 1 on both). Cox regression with a time-fixed exposure history (n = 45) or time-varying covariates (n = 13) were the most frequently used methods. Only four studies used g-methods, which are designed to adjust for time-varying confounding. Risk of bias arose primarily from inadequate adjustment for time-varying confounders, participant selection, exposure classification and changes from measured exposure. Despite heterogeneity in methods, most studies found that being consistently or increasingly active over adulthood was associated with lower all-cause and cardiovascular-disease mortality compared with being always inactive. Few studies examined physical-activity changes and cancer mortality or effects of sedentary-behaviour changes on mortality outcomes.Conclusions: Accumulating more evidence using longitudinal data while addressing the methodological challenges would provide greater insight into the health effects of initiating or maintaining a more active and less sedentary lifestyle. [ABSTRACT FROM AUTHOR]

Background: Prenatal exposure to maternal smoking is detrimental to child health but its association with risk of cancer has seldom been investigated. Maternal smoking induces widespread and long-lasting DNA methylation changes, which we study here for association with risk of cancer in adulthood.Methods: Eight prospective case-control studies nested within the Melbourne Collaborative Cohort Study were used to assess associations between maternal-smoking-associated methylation marks in blood and risk of several cancers: breast (n = 406 cases), colorectal (n = 814), gastric (n = 166), kidney (n = 139), lung (n = 327), prostate (n = 847) and urothelial (n = 404) cancer and B-cell lymphoma (n = 426). We used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between cancer and five methylation scores calculated as weighted averages for 568, 19, 15, 28 and 17 CpG sites. Models were adjusted for confounders, including personal smoking history (smoking status, pack-years, age at starting and quitting) and methylation scores for personal smoking.Results: All methylation scores for maternal smoking were strongly positively associated with risk of urothelial cancer. Risk estimates were only slightly attenuated after adjustment for smoking history, other potential confounders and methylation scores for personal smoking. Potential negative associations were observed with risk of lung cancer and B-cell lymphoma. No associations were observed for other cancers.Conclusions: We found that methylation marks of prenatal exposure to maternal smoking are associated with increased risk of urothelial cancer. Our study demonstrates the potential for using DNA methylation to investigate the impact of early-life, unmeasured exposures on later-life cancer risk. [ABSTRACT FROM AUTHOR]

Background: Self-reported physical activity is inaccurate, yet few investigators attempt to adjust for measurement error when estimating risks for health outcomes. We estimated what the association between self-reported physical activity and colorectal cancer risk would be if physical activity had been assessed using accelerometry instead.Methods: We conducted a validation study in which 235 Australian adults completed a telephone-administered International Physical Activity Questionnaire (IPAQ), and wore an accelerometer (Actigraph GT3X+) for 7 days. Using accelerometer-assessed physical activity as the criterion measure, we calculated validity coefficients and attenuation factors using a structural equation model adjusted for age, sex, education and body mass index. We then used a regression calibration approach to apply the attenuation factors to data from the Melbourne Collaborative Cohort Study (MCCS) to compute bias-adjusted hazard ratios (HR) and 95% confidence intervals (CI).Results: Average daily minutes of physical activity from the short form of the International Physical Activity Questionnaire (IPAQ-short) were substantially higher than accelerometer-measured duration (55 versus 32 min). The validity coefficient (0.32; 95% CI: 0.20, 0.43) and attenuation factor (0.20; 95% CI: 0.12, 0.28) were low. The HRs for colorectal cancer risk for high (75th percentile; 411 min/week) versus low (25th percentile; 62 min/week) levels of self-reported physical activity were 0.95 (95% CI: 0.87, 1.05) before and 0.78 (95% CI: 0.47, 1.28) after bias adjustment.Conclusions: Over-estimation of physical activity by the IPAQ-short substantially attenuates the association between physical activity and colorectal cancer risk, suggesting that the protective effect of physical activity has been previously underestimated. [ABSTRACT FROM AUTHOR]

Background: : Observational studies have reported that weight loss in later life is associated with an increased risk of mortality. However, the association with weight gain is unclear. We conducted a systematic review and meta-analysis of prospective studies assessing the association of weight gain and loss, and mortality.Methods: : We searched PubMed, Scopus and Web of Science for articles published before 5 September 2015. We included prospective studies that reported enough information to extract hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) for the association between weight gain and/or weight loss, and all-cause and cause-specific mortality. The estimates were pooled using a random-effects model. Meta-regression models were fitted to explore sources of potential between-study heterogeneity.Results: : A total of 25 (providing data from 437 772 participants with 34 038 deaths from all causes) and 24 studies (434 694 participants with 31 978 deaths) presented results for the exposures, weight loss and weight gain. Weight loss compared with a stable weight was associated with an increased risk of all-cause (pooled HR: 1.45; 95% CI: 1.34, 1.58), and cardiovascular disease (CVD) mortality (1.50; 1.32, 1.70) and a slightly increased risk of cancer mortality (1.19; 0.97, 1.46). Weight gain was associated with an increased risk of CVD mortality (1.21; 1.07, 1.36) and a slightly increased risk of all-cause mortality (1.07; 1.01, 1.13) and cancer mortality (1.04; 0.96, 1.13). Considerable heterogeneity was observed; the method used to ascertain body size and the proportion of the baseline sample included in the final analysis explained most of the heterogeneity.Conclusion: : Weight loss and weight gain in midlife are associated with increased risk of all-cause and CVD mortality. [ABSTRACT FROM AUTHOR]

Background Greater physical activity (PA) and less sitting time (ST) have been associated with lower breast cancer (BC) risk in observational studies, but causality is undetermined. Mendelian randomization (MR) investigates causality by using genotype to simulate randomized trials within observational data. A recent summary-data MR study assessed PA and BC by estrogen-receptor (ER) status. We aimed to examine PA and ST in relation to invasive BC risk overall and by molecular subtype. Methods We performed two-sample MR using individual-level Breast Cancer Association Consortium data from 125,684 women (69,869 cases), and summary-level UK Biobank genetic data for the exposure (n = 91,105). We used imputed single nucleotide polymorphisms (SNPs) previously associated (p < 5x10-8) with accelerometer-measured PA (n-SNPs=5) or ST (n = 6). We estimated odds ratios (OR) from inverse-variance weighted MR. Results Greater PA was associated with lower risk of BC (OR = 0.48;95%CI=0.30-0.78 per standard deviation [SD] in activity). Estimates were inverse for all subtypes, particularly ER + (OR=0.45; 95%CI=0.25-0.83), PR + (OR=0.43;95%CI=0.22-0.85), and HER2 + (OR = 0.48; 95%CI=0.26-0.89). Greater ST was associated with higher risk of hormone-receptor-negative tumours, particularly triple-negative (ER-/PR-/HER2-) (OR = 2.04; 95%CI=1.06-3.93 per SD in ST). Estimates overall and for most other subtypes were elevated but had wide CIs crossing null. Sensitivity analyses (weighted-median MR and MR-Egger) did not suggest strong pleiotropic effects for either exposure. Conclusions Greater PA and lower ST reduces risk of all breast cancers, and hormone-receptor negative tumours, respectively. More widespread adoption of active lifestyles will lower burden from the most common cancer in women. Key messages More active and less sedentary lifestyles reduce risk of breast cancer. [ABSTRACT FROM AUTHOR]

de Klerk NH (NH and MRC Unit of Epidemiology and Preventive Medicine, Department of Medicine, University of Western Australia, Western Australia 6009), English DR and Armstrong BK. A review of the effects of random measurement error on relative risk estimates in epidemiological studies. 1989; : 705–712. Many articles in the recent epidemiological literature have discussed the effects of random error and misclassification on effect estimation, but many of these have been unclear and hard to follow. This paper reviews and interprets many of these and summarizes the use of the correlation coefficient in assessing the likely effect of measurement error on relative risk estimates for variables that are either continuous or ordered. A table of expected values of relative risks (RRs) calculated in different ways for different levels of random error is presented and the typically large expected attenuation in RR values is shown. The recommendation of taking repeated or multiple measurements whenever possible is endorsed. [ABSTRACT FROM PUBLISHER]