Epidemiological evidence suggests that vitamin D deficiency is associated with increased mortality, but it is unclear whether this is explained by reverse causation, and if there are specific causes ...of death for which vitamin D might be important. We conducted a systematic review of observational studies investigating associations between circulating 25-hydroxyvitamin D (25(OH)D) concentration and all-cause or cause-specific mortality in generally healthy populations. Relevant studies were identified using PubMed and EMBASE searches. After screening 722 unique records and removing those that were ineligible, 84 articles were included in this review. The vast majority of studies reported inverse associations between 25(OH)D concentration and all-cause mortality. This association appeared to be non-linear, with progressively lower mortality with increasing 25(OH)D up to a point, beyond which there was no further decrease. There is moderate evidence that vitamin D status is inversely associated with cancer mortality and death due to respiratory diseases, while for cardiovascular mortality, there is weak evidence of an association in observational studies, which is not supported by the data from intervention or Mendelian randomization studies. The relationship between vitamin D status and other causes of death remains uncertain due to limited data. Larger long-term studies are required to clarify these associations.
We examined associations between sex‐specific alcohol intake trajectories and alcohol‐related cancer risk using data from 22 756 women and 15 701 men aged 40 to 69 years at baseline in the Melbourne ...Collaborative Cohort Study. Alcohol intake for 10‐year periods from age 20 until the decade encompassing recruitment, calculated using recalled beverage‐specific frequency and quantity, was used to estimate group‐based sex‐specific intake trajectories. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for primary invasive alcohol‐related cancer (upper aerodigestive tract, breast, liver and colorectum). Three distinct alcohol intake trajectories for women (lifetime abstention, stable light, increasing moderate) and six for men (lifetime abstention, stable light, stable moderate, increasing heavy, early decreasing heavy, late decreasing heavy) were identified. 2303 incident alcohol‐related cancers were diagnosed during 485 525 person‐years in women and 789 during 303 218 person‐years in men. For men, compared with lifetime abstention, heavy intake (mean ≥ 60 g/day) at age 20 to 39 followed by either an early (from age 40 to 49) (early decreasing heavy; HR = 1.75, 95% CI: 1.25‐2.44) or late decrease (from age 60 to 69) (late decreasing heavy; HR = 1.94, 95% CI: 1.28‐2.93), and moderate intake (mean <60 g/day) at age 20 to 39 increasing to heavy intake in middle‐age (increasing heavy; HR = 1.45, 95% CI: 1.06‐1.97) were associated with increased risk of alcohol‐related cancer. For women, compared with lifetime abstention, increasing intake from age 20 (increasing moderate) was associated with increased alcohol‐related cancer risk (HR = 1.25, 95% CI: 1.06‐1.48). Similar associations were observed for colorectal (men) and breast cancer. Heavy drinking during early adulthood might increase cancer risk later in life.
What's new?
Alcoholic beverages are a known risk factor for oral cavity, pharynx, larynx, esophagus, liver, colorectal and breast cancers. Unlike most previous studies of alcohol intake and cancer risk, here the authors examined associations of longitudinal drinking trajectories across the lifespan. Compared with lifelong non‐drinking, they observed an increased cancer risk associated with heavy drinking during early adulthood, even when the intake had ceased by middle age, and with drinking that increased during the life‐course. The findings of this large prospective study point to critical timelines related to alcohol‐related cancer etiology and prevention during the adult lifespan.
We are very pleased to introduce Ten to Men, the Australian Longitudinal Study on Male Health. Ten to Men is, to our knowledge, the largest national all-male cohort study in the world. It involves ...15,988 males who were aged between 10 and 55 years when we recruited them in 2013/14. Together, the articles in this collection provide an overview of the study's methods, examples of some of the key questions it can answer, and guidance for researchers wishing to use it. Perhaps most importantly, the articles demonstrate the enormous potential Ten to Men has to make a real difference to our understanding of male health and the factors that influence it.
Studies investigating the association of food and nutrient consumption with the risk of urothelial cell carcinoma (UCC) have produced mixed results. We used three common dietary scores, the ...Mediterranean Diet Score (MDS), the Alternate Healthy Eating Index 2010 (AHEI‐2010) and the Dietary Inflammatory Index (DII) to assess the evidence of an association between diet and the risk of UCC. Over a median follow‐up time of 21.3 years, 379 incident UCC cases were diagnosed. Dietary scores were calculated using data from a 121‐item food frequency questionnaire administered at baseline. We used Cox models to compute hazard ratios (HR) for the association between dietary scores (per one standard deviation) and UCC risk. In order to reflect overall adherence to a healthy diet, a metascore was constructed by summing the quintiles of each of the three scores. None of the dietary scores was associated with the risk of UCC overall. A healthier diet was found to be inversely associated with the risk of invasive (MDS: HR = 0.86, 95% CI: 0.74–1.00, metascore: HR = 0.84, 95% CI: 0.71–0.98), but not superficial disease (heterogeneity between subtypes p = 0.04 and p = 0.03, respectively). Results were consistent but weaker for the DII and the AHEI‐2010. We found some evidence of effect modification by smoking, in particular for the metascore (Current: HR = 0.77, 95% CI: 0.58–1.01, Former: HR = 0.77, 95% CI: 0.64–0.92, Never: HR = 1.01, 95% CI: 0.81–1.26, p for heterogeneity = 0.05). A healthy diet may be protective against the risk of invasive, but not superficial, UCC. Promoting healthy dietary habits may help lower the risk of invasive UCC, especially for current and former smokers.
What's new?
When components of the food we eat interact with the lining of the urethra on their way out, they can influence urothelial cell carcinoma. Various studies have tried to quantify the impact of individual nutrients on UCC risk; this study instead focused on the diet as a whole. Each person's dietary pattern received a score on three separate scales that reflect different philosophies of healthy eating, but the scores did not correlate with overall urothelial cell cancer risk. The authors did find that people with a healthier diet had a lower risk of invasive cancers, and healthier eating especially benefitted smokers.
Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate ...levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol–CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case‐control and 11 nested case‐control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study‐specific results were pooled using fixed‐effects meta‐analysis. Compared to non‐/occasional drinking (≤1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio OR: 0.92, 95% confidence interval CI: 0.88–0.98, p = 0.005), heavy drinking (2–3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99–1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11–1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J‐shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.
What's new?
Heavy drinking is associated with increased colorectal cancer (CRC) risk, but there's debate about the impact of moderate drinking. Here, the authors conducted a combined analysis of 16 studies comprising 14,276 cases and 15,802 controls. By their analysis, drinking 1‐2 alcoholic beverages per day was associated with a reduced risk of CRC, compared with rare or no alcohol consumption. With 3 or more drinks per day, CRC risk rises. The authors suggest that moderate alcohol consumption may reduce inflammation and DNA damage, although they acknowledge that more research is needed to understand the biochemical mechanism at work.
BACKGROUND: Dietary fatty acids may be associated with diabetes but are difficult to measure accurately. OBJECTIVE: We aimed to investigate the associations of fatty acids in plasma and diet with ...diabetes incidence. DESIGN: This was a prospective case-cohort study of 3737 adults aged 36-72 y. Fatty acid intake (/kJ) and plasma phospholipid fatty acids (%) were measured at baseline, and diabetes incidence was assessed by self-report 4 y later. Logistic regression excluding (model 1) and including (model 2) body mass index and waist-hip ratio was used to calculate odds ratios (ORs) for plasma phospholipid and dietary fatty acids. RESULTS: In plasma phospholipid, positive associations with diabetes were seen for stearic acid OR model 1, highest versus lowest quintile: 4.14 (95% CI: 2.65, 6.49), P for trend < 0.0001 and total saturated fatty acids OR model 1: 3.76 (2.43, 5.81), P for trend < 0.0001, whereas an inverse association was seen for linoleic acid OR model 1: 0.22 (0.14, 0.36), P for trend < 0.0001. Dietary linoleic OR model 1: 1.77 (1.19, 2.64), P for trend = 0.002, palmitic OR model 1: 1.65 (1.12, 2.43), P for trend = 0.012, and stearic OR model 1: 1.46 (1.00, 2.14), P for trend = 0.030 acids were positively associated with diabetes incidence before adjustment for body size. Within each quintile of linoleic acid intake, cases had lower baseline plasma phospholipid linoleic acid proportions than did controls. CONCLUSIONS: Dietary saturated fat intake is inversely associated with diabetes risk. More research is required to determine whether linoleic acid is an appropriate dietary substitute.
The association between change in weight or body mass index, and mortality is widely reported, however, both measures fail to account for fat distribution. Change in waist circumference, a measure of ...central adiposity, in relation to mortality has not been studied extensively.
We investigated the association between mortality and changes in directly measured waist circumference, hips circumference and weight from baseline (1990-1994) to wave 2 (2003-2007) in a prospective cohort study of people aged 40-69 years at baseline. Cox regression, with age as the time metric and follow-up starting at wave 2, adjusted for confounding variables, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for change in body size in relation to mortality from all causes, cardiovascular disease and cancer.
There were 1465 deaths (109 cancer, 242 cardiovascular disease) identified during an average 7.7 years of follow-up from 21 298 participants. Compared to minimal increase in body size, loss of waist circumference (HR: 1.26; 95% CI: 1.09-1.47), weight (1.80; 1.54-2.11), or hips circumference (1.35; 1.15-1.57) were associated with an increased risk of all-cause mortality, particularly for older adults. Weight loss was associated with cardiovascular disease mortality (2.40; 1.57-3.65) but change in body size was not associated with obesity-related cancer mortality.
This study confirms the association between weight loss and increased mortality from all-causes for older adults. Based on evidence from observational cohort studies, weight stability may be the recommended option for most adults, especially older adults.
Methylation marks of exposure to health risk factors may be useful markers of cancer risk as they might better capture current and past exposures than questionnaires, and reflect different individual ...responses to exposure. We used data from seven case-control studies nested within the Melbourne Collaborative Cohort Study of blood DNA methylation and risk of colorectal, gastric, kidney, lung, prostate and urothelial cancer, and B-cell lymphoma (N cases = 3123). Methylation scores (MS) for smoking, body mass index (BMI), and alcohol consumption were calculated based on published data as weighted averages of methylation values. Rate ratios (RR) and 95% confidence intervals for association with cancer risk were estimated using conditional logistic regression and expressed per SD increase of the MS, with and without adjustment for health-related confounders. The contribution of MS to discriminate cases from controls was evaluated using the area under the curve (AUC). After confounder adjustment, we observed: large associations (RR = 1.5-1.7) with lung cancer risk for smoking MS; moderate associations (RR = 1.2-1.3) with urothelial cancer risk for smoking MS and with mature B-cell neoplasm risk for BMI and alcohol MS; moderate to small associations (RR = 1.1-1.2) for BMI and alcohol MS with several cancer types and cancer overall. Generally small AUC increases were observed after inclusion of several MS in the same model (colorectal, gastric, kidney, urothelial cancers: +3%; lung cancer: +7%; B-cell neoplasms: +8%). Methylation scores for smoking, BMI and alcohol consumption show independent associations with cancer risk, and may provide some improvements in risk prediction.
Abstract
No randomized controlled trial has evaluated the effect of long-term alcohol interventions on mortality. Results reported in existing observational studies may be subject to selection bias ...and time-varying confounding. Using data from the Australian Longitudinal Study on Women’s Health 1946–1951 birth cohort, collected regularly from 1996–2016, we estimated all-cause and cancer mortality had women been assigned various alcohol interventions (in categories ranging from 0 to >30 g/day ethanol, or reduced to ≤20 g/day if higher) at baseline, and had they maintained these levels of consumption. The cumulative risks for all-cause and cancer mortality were 5.6% (10,118 women followed for 20 years) and 2.9% (18 years), respectively. For all-cause and cancer mortality, baseline ethanol up to 30 g/day showed lower risk and >30 g/day showed higher risk relative to abstention. Had women sustainedly followed the interventions, a similar relationship was observed for all-cause mortality. However, the negative association observed for intakes ≤30 g/day and positive association for intakes >30 g/day was not evident for cancer mortality. Our findings suggest that all-cause mortality could have been lower than observed if this cohort of women had consumed some alcohol (no more than 30 g/day) rather than no consumption, but cancer mortality might not.
To investigate whether supplementing older adults with monthly doses of vitamin D alters the incidence of major cardiovascular events.
Randomised, double blind, placebo controlled trial of monthly ...vitamin D (the D-Health Trial). Computer generated permuted block randomisation was used to allocate treatments.
Australia from 2014 to 2020.
21 315 participants aged 60-84 years at enrolment. Exclusion criteria were self-reported hypercalcaemia, hyperparathyroidism, kidney stones, osteomalacia, sarcoidosis, taking >500 IU/day supplemental vitamin D, or unable to give consent because of language or cognitive impairment.
60 000 IU/month vitamin D
(n=10 662) or placebo (n=10 653) taken orally for up to five years. 16 882 participants completed the intervention period: placebo 8270 (77.6%); vitamin D 8552 (80.2%).
The main outcome for this analysis was the occurrence of a major cardiovascular event, including myocardial infarction, stroke, and coronary revascularisation, determined through linkage with administrative datasets. Each event was analysed separately as secondary outcomes. Flexible parametric survival models were used to estimate hazard ratios and 95% confidence intervals.
21 302 people were included in the analysis. The median intervention period was five years. 1336 participants experienced a major cardiovascular event (placebo 699 (6.6%); vitamin D 637 (6.0%)). The rate of major cardiovascular events was lower in the vitamin D group than in the placebo group (hazard ratio 0.91, 95% confidence interval 0.81 to 1.01), especially among those who were taking cardiovascular drugs at baseline (0.84, 0.74 to 0.97; P for interaction=0.12), although the P value for interaction was not significant (<0.05). Overall, the difference in standardised cause specific cumulative incidence at five years was -5.8 events per 1000 participants (95% confidence interval -12.2 to 0.5 per 1000 participants), resulting in a number needed to treat to avoid one major cardiovascular event of 172. The rate of myocardial infarction (hazard ratio 0.81, 95% confidence interval 0.67 to 0.98) and coronary revascularisation (0.89, 0.78 to 1.01) was lower in the vitamin D group, but there was no difference in the rate of stroke (0.99, 0.80 to 1.23).
Vitamin D supplementation might reduce the incidence of major cardiovascular events, although the absolute risk difference was small and the confidence interval was consistent with a null finding. These findings could prompt further evaluation of the role of vitamin D supplementation, particularly in people taking drugs for prevention or treatment of cardiovascular disease.
ACTRN12613000743763.
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