Cardiovascular risk factors and lifestyle behaviours in relation to longevity: a Mendelian randomization study.

BACKGROUND: The American Heart Association introduced the Life's Simple 7 initiative to improve cardiovascular health by modifying cardiovascular risk factors and lifestyle behaviours. It is unclear whether these risk factors are causally associated with longevity. OBJECTIVES: This study aimed to investigate causal associations of Life's Simple 7 modifiable risk factors, as well as sleep and education, with longevity using the two-sample Mendelian randomization design. METHODS: Instrumental variables for the modifiable risk factors were obtained from large-scale genome-wide association studies. Data on longevity beyond the 90th survival percentile were extracted from a genome-wide association meta-analysis with 11,262 cases and 25,483 controls whose age at death or last contact was ≤ the 60th survival percentile. RESULTS: Risk factors associated with a lower odds of longevity included the following: genetic liability to type 2 diabetes (OR 0.88; 95% CI: 0.84;0.92), genetically predicted systolic and diastolic blood pressure (per 1-mmHg increase: 0.96; 0.94;0.97 and 0.95; 0.93;0.97), body mass index (per 1-SD increase: 0.80; 0.74;0.86), low-density lipoprotein cholesterol (per 1-SD increase: 0.75; 0.65;0.86) and smoking initiation (0.75; 0.66;0.85). Genetically increased high-density lipoprotein cholesterol (per 1-SD increase: 1.23; 1.08;1.41) and educational level (per 1-SD increase: 1.64; 1.45;1.86) were associated with a higher odds of longevity. Fasting glucose and other lifestyle factors were not significantly associated with longevity. CONCLUSION: Most of the Life's Simple 7 modifiable risk factors are causally related to longevity. Prevention strategies should focus on modifying these risk factors and reducing education inequalities to improve cardiovascular health and longevity.

Interleukin-1 receptor antagonist, interleukin-2 receptor alpha subunit and amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: To clarify the causal associations of interleukin-1 receptor antagonist (IL-1ra) and interleukin-2 receptor alpha subunit (IL-2rα) with the risk of amyotrophic lateral sclerosis (ALS). METHODS: A two-sample Mendelian randomization study design was employed. Single-nucleotide polymorphisms associated with IL-1ra (n = 2) and IL-2rα (n = 1) at the genome-wide significance level were used as unbiased instrumental variables. Summary-level data for ALS were obtained from Project MinE, an international collaboration consortium with 12 577 ALS cases and 23 475 controls of European descent. RESULTS: Genetic predisposition to higher levels of IL-1ra was significantly associated with lower odds of ALS. For a 1-SD increase of circulating IL-1ra levels, the odds ratio of ALS was 0.64 (95% confidence intervals, 0.46-0.88; P = 0.005). There was a borderline inverse association between IL-2rα levels and ALS (odds ratio, 0.91; 95% confidence intervals, 0.83-1.00; P = 0.058). CONCLUSIONS: Interleukin-1 receptor antagonist levels were inversely associated with ALS, suggesting that interleukin-1 inhibitors may lower the risk of this always fatal disease. The role of IL-2rα levels in ALS needs further verification in causal inference studies with larger sample sizes.

Coffee, tea, and caffeine intake and amyotrophic lateral sclerosis mortality in a pooled analysis of eight prospective cohort studies.

BACKGROUND AND PURPOSE: Caffeine is associated with a lower risk of some neurological diseases, but few prospective studies have investigated caffeine intake and risk of amyotrophic lateral sclerosis (ALS) mortality. We therefore determined associations between coffee, tea and caffeine intake, and risk of ALS mortality. METHODS: We conducted pooled analyses of eight international, prospective cohort studies, including 351 565 individuals (120 688 men and 230 877 women). We assessed coffee, tea and caffeine intake using validated food-frequency questionnaires administered at baseline. We used Cox regression to estimate study- and sex-specific risk ratios and 95% confidence intervals (CI) for ALS mortality, which were then pooled using a random-effects model. We conducted analyses using cohort-specific tertiles, absolute common cut-points and continuous measures of all exposures. RESULTS: During follow-up, 545 ALS deaths were documented. We did not observe statistically significant associations between coffee, tea or caffeine intake and risk of ALS mortality. The pooled multivariable risk ratio (MVRR) for ≥3 cups per day vs. >0 to <1 cup per day was 1.04 (95% CI, 0.74-1.47) for coffee and 1.17 (95% CI, 0.77-1.79) for tea. The pooled MVRR comparing the highest with the lowest tertile of caffeine intake (mg/day) was 0.99 (95% CI, 0.80-1.23). No statistically significant results were observed when exposures were modeled as tertiles or continuously. CONCLUSIONS: Our results do not support associations between coffee, tea or total caffeine intake and risk of ALS mortality.

Coffee consumption and risk of aortic valve stenosis: A prospective study.

BACKGROUND AND AIMS: Coffee contains many biologically active compounds with potential adverse or beneficial effects on the cardiovascular system. Whether coffee consumption is associated with the risk of aortic valve stenosis (AVS) is unknown. The purpose of this study was therefore to examine the association between coffee consumption and AVS incidence. METHODS AND RESULTS: This prospective study included 71 178 men and women who provided information on their coffee consumption through a questionnaire at baseline. Incident cases of AVS were identified through linkage with the Swedish National Patient and Cause of Death Registers. During a mean follow-up of 15.2 years, 1295 participants (777 men and 518 women) were diagnosed with AVS. Coffee consumption was positively associated with risk of AVS in a dose-response manner after adjustment for age, sex, smoking, and other risk factors (P-trend = 0.005). The multivariable hazard ratios were was 1.11 (95% confidence interval 1.04-1.19) per 2 cups/day increase of coffee consumption and 1.65 (95% confidence interval 1.10-2.48) when comparing the highest (≥6 cups/day) with the lowest (<0.5 cup/day) category of coffee consumption. The association was not modified by other risk factors. CONCLUSIONS: This study provides novel evidence that high coffee consumption is associated with an increased risk of AVS.

Enhanced ventricular-arterial coupling during a 2-year physical activity programme in patients with rheumatoid arthritis: a prospective substudy of the physical activity in rheumatoid arthritis 2010 trial.

OBJECTIVE: To establish how guided physical activity in patients with rheumatoid arthritis (RA) without known cardiovascular disease affected vascular and cardiac function, and how these two entities were prospectively interconnected in this patient group. METHODS: Prospective substudy of 29 participants in the Physical Activity in RA (PARA) 2010 trial. All subjects were examined at baseline, at year 1 and 2 with measures of pulse wave velocity and arterial augmentation index, as well as echocardiographic evaluation of diastolic parameters and ventricular-arterial coupling. Muscle strength and aerobic exercise capacity were assessed at baseline and yearly. All participants performed physiotherapist-guided aerobic and muscle strength exercise during 2 years and were reminded through SMS to report physical activity progress. RESULTS: This cohort of patients with RA exhibited increased vascular stiffness despite normal blood pressure. At baseline, lower muscle strength was associated with increased vascular stiffness (ß = 0.68; P = 0.004), whereas lower aerobic working capacity was associated with left ventricular diastolic dysfunction (ß = 0.85; P = 0.03). There was a significant positive correlation between vascular stiffness and diastolic dysfunction at baseline (R2  = 0.64) and for the changes in those parameters observed during 2 years of guided physical activity. Finally, a significant improvement in ventricular-arterial coupling was observed after exercise (P < 0.001). CONCLUSION: These results indicate that although differentially associated with physical capacity parameters, improved vascular stiffness and improved diastolic dysfunction are interrelated, and that an optimization of the ventricular-arterial coupling may contribute to the beneficial effects of physical activity in patients with RA.

Combined impact of healthy lifestyle factors on lifespan: two prospective cohorts.

BACKGROUND: The impact of multiple healthy lifestyle factors on survival time is unclear. OBJECTIVE: The aim of this study was to examine differences in survival time associated with a healthy lifestyle versus a less healthy lifestyle. METHODS: This study consisted of 33 454 men (Cohort of Swedish Men) and 30 639 women (Swedish Mammography Cohort) aged 45-83 years and free of cancer and cardiovascular disease at baseline. The healthy lifestyle factors included the following: (i) nonsmoking; (ii) physical activity at least 150 min per week; (iii) alcohol consumption of 0-14 drinks per week; (iv) and healthy diet defined as a modified Dietary Approaches to Stop Hypertension Diet score above the median. Cox proportional hazards regression models and Laplace regression were used to estimate, respectively, hazard ratios of all-cause mortality and differences in survival time. RESULTS: During follow-up from 1998 through 2014, 8630 deaths amongst men and 6730 deaths amongst women were ascertained through linkage to the Swedish Cause of Death Register. Each of the four healthy lifestyle factors was inversely associated with all-cause mortality and increased survival time. Compared with individuals with no or one healthy lifestyle factor, the multivariable hazard ratios of all-cause mortality for individuals with all four health behaviours were 0.47 (95% 95% confidence interval [CI]: 0.44-0.51) in men and 0.39 (95% CI: 0.35-0.44) in women. This corresponded to a difference in survival time of 4.1 (95% CI: 3.6-4.6) years in men and 4.9 (95% CI: 4.3-5.6) years in women. CONCLUSION: Adopting healthy lifestyle behaviours may markedly increase lifespan.

Alcohol consumption, cigarette smoking and incidence of aortic valve stenosis.

BACKGROUND: Alcohol consumption and cigarette smoking are modifiable lifestyle factors with important impact on public health. It is unclear whether these factors influence the risk of aortic valve stenosis (AVS). OBJECTIVE: To investigate the associations of alcohol consumption and smoking, including smoking intensity and time since cessation, with AVS incidence in two prospective cohorts. METHODS: This analysis was based on data from the Swedish Mammography Cohort and the Cohort of Swedish Men, comprising 69 365 adults without cardiovascular disease at baseline. Participants were followed for AVS incidence and death by linkage to the Swedish National Patient and Causes of Death Registers. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated by Cox proportional hazards regression. RESULTS: Over a mean follow-up of 15.3 years, 1249 cases of AVS (494 in women and 755 in men) were recorded. Compared with never drinkers of alcohol (lifelong abstainers), the risk of AVS was significantly lower in current light drinkers (1-6 drinks per week [1 drink = 12 g alcohol]; multivariable HR 0.82; 95% CI: 0.68-0.99). The risk of AVS increased with increasing smoking intensity. Compared with never smokers, the HR was 1.46 (95% CI: 1.16-1.85) in current smokers of ≥30 pack-years. Former smokers who had quit smoking 10 or more years previously had similar risk for AVS as never smokers. CONCLUSIONS: This study suggests that current light alcohol consumption is associated with a lower risk of AVS, and indicates that the association between smoking and AVS risk is reversible.

Fish consumption and all-cause mortality in a cohort of Swedish men and women.

BACKGROUND: Epidemiological studies of fish consumption and all-cause mortality have provided inconsistent results. OBJECTIVE: We examined the dose-response association between fish consumption and mortality from all causes in a large population-based cohort of Swedish men and women. METHODS: The study included 72 522 participants (33 973 women and 38 549 men), aged 45-83 years, from the Swedish Mammography Cohort and the Cohort of Swedish Men. Information on fish consumption was obtained through a self-administered questionnaire in 1997. Participants were followed for 17 years (1 January 1998 to 31 December 2014), and data on death and causes of death were ascertained through linkage to the Swedish Cause of Death Register. We used Cox proportional hazard regression to estimate hazard ratios (HRs) of death. Fish consumption was evaluated as a continuous predictor, flexibly modelled with restricted cubic splines to assess potential nonlinear associations. RESULTS: During follow-up, 16 730 deaths (7168 women and 9562 men) were recorded. The dose-response association between fish consumption and all-cause mortality was U-shaped. Compared with the median fish consumption (women: 25.0; men: 30.5 g day-1 ), lower levels of consumption were progressively associated with higher mortality risk up to 25% for women [HR 1.25; 95% confidence interval (CI): 1.11, 1.40] and 19% for men (HR 1.19; 95% CI: 1.07, 1.32) with no reported consumption. Increasingly higher levels of fish consumption were associated with higher mortality risk only amongst women, with a 39% higher mortality risk amongst women reporting the highest level of fish consumption (80 g day-1 ; HR 1.39; 95% CI: 1.15, 1.68). CONCLUSION: These results indicate a U-shaped association between fish consumption and all-cause mortality, particularly amongst women.

Sex differences in the association between smoking and abdominal aortic aneurysm.

BACKGROUND: It is unclear whether recommendations about ultrasound screening programmes for abdominal aortic aneurysm (AAA) among men should be extended to include women who smoke. The aim was to examine sex-specific dose-response associations between AAA risk and smoking status, pack-years smoked and time since smoking cessation. METHODS: Women in the Swedish Mammography Cohort and men in the Cohort of Swedish Men were followed up from 1998 to 2011. AAA was identified through linkage of the cohorts to the Swedish Inpatient Register and the Swedish National Register for Vascular Surgery (Swedvasc), and not through general ultrasound screening. Associations were estimated with Cox proportional hazards models. RESULTS: The cohorts included 35 550 women and 42 596 men, aged 46-84 years. During follow-up, AAA was identified in 199 women and 958 men. The incidence of AAA per 100 000 person-years was 76 among men who never smoked and 136 among women who currently smoke. Regarding AAA risk, women were more sensitive to current smoking (Pinteraction = 0·002). Compared with never smokers, the hazard ratio (HR) for AAA in current smokers with more than 20 pack-years was 10·97 (95 per cent confidence interval 7·41 to 16·26) among women and 6·55 (5·36 to 7·99) among men. Following smoking cessation, women had a more rapid decline in excess risk (Pinteraction < 0·001). The risk was halved after 11 years (HR 0·51, 0·32 to 0·81) among women and after 23 years (HR 0·50, 0·42 to 0·60) among men. CONCLUSION: There were sex differences in the associations between smoking status and AAA risk. These data support further investigation of targeted AAA screening among women who smoke.

Dietary exposure to polychlorinated biphenyls is associated with increased risk of stroke in women.

OBJECTIVE: The potentially beneficial effects of fish consumption on stroke may be modified by major food contaminants in fish. Polychlorinated biphenyls (PCBs) in particular are proposed to play a role in the aetiology of stroke. The aim of this study was to assess the association between dietary PCB exposure and stroke risk with the intake of long-chain omega-3 fish fatty acids and fish consumption. DESIGN: The prospective population-based Swedish Mammography Cohort was examined. It was comprised of 34,591 women free of cardiovascular diseases and cancer at baseline in 1997 and followed up for 12 years. Validated estimates of dietary PCB exposure were obtained via a food frequency questionnaire at baseline. Incident cases of stroke were ascertained through register linkage. RESULTS: During 12 years of follow-up (397,309 person-years), there were 2015 incident cases of total stroke (1532 ischaemic strokes, 216 intracerebral haemorrhages, 94 subarachnoid haemorrhages and 173 unspecified strokes). Multivariable-adjusted relative risks (RR), controlled for known stroke risk factors and fish consumption, were 1.67 [95% confidence interval (CI), 1.29-2.17] for total stroke, 1.61 (95% CI, 1.19-2.17) for ischaemic stroke and 2.80 (95% CI, 1.42-5.55) for haemorrhagic stroke for women in the highest quartile of dietary PCB exposure (median 288 ng day(-1) ) compared with women in the lowest quartile (median 101 ng day(-1) ). CONCLUSION: Dietary exposure to PCBs was associated with an increased stroke risk in women, especially haemorrhagic stroke. The results provide important information regarding the risk-benefit analysis of fish consumption, particularly for cerebrovascular disease prevention.

Obesity and abdominal aortic aneurysm.

BACKGROUND: The relationship between obesity and abdominal aortic aneurysm (AAA) is unclear. An observational cohort study was undertaken to examine the associations between waist circumference as a measure of abdominal adiposity, and between body mass index (BMI) as a measure of total adiposity, and risk of AAA. METHODS: Data were used from the population-based Swedish Mammography Cohort and the Cohort of Swedish Men, involving 63,655 men and women, aged 46-84 years. Between 1998 and 2009, 597 patients with incident AAA defined by relevant clinical events were identified by linkage to the Swedish Inpatient Register and the Swedish Vascular Registry. Cox proportional hazards models were used to estimate relative risks (RRs) with 95 per cent confidence intervals. RESULTS: In multivariable analysis, individuals with an increased waist circumference had a 30 per cent higher risk of AAA (RR 1·30, 95 per cent confidence interval 1·05 to 1·60) compared with those with a normal waist circumference. The risk of AAA increased by 15 per cent (RR 1·15, 1·05 to 1·26) per 5-cm increment of waist circumference up to the level 100 cm for men and 88 cm for women. There was no association between BMI and risk of AAA. CONCLUSION: Abdominal, but not total, adiposity was associated with an increased risk of incident AAA. A threshold was observed at a waist circumference of 100 cm for men and 88 cm for women.

Red and processed meat consumption and risk of pancreatic cancer: meta-analysis of prospective studies.

BACKGROUND: Whether red and processed meat consumption is a risk factor for pancreatic cancer remains unclear. We conducted a meta-analysis to summarise the evidence from prospective studies of red and processed meat consumption and pancreatic cancer risk. METHODS: Relevant studies were identified by searching PubMed and EMBASE databases through November 2011. Study-specific results were pooled using a random-effects model. RESULTS: Eleven prospective studies, with 6643 pancreatic cancer cases, were included in the meta-analysis. An increase in red meat consumption of 120 g per day was associated with an overall relative risk (RR) of 1.13 (95% confidence interval (CI)=0.93-1.39; P(heterogeneity)<0.001). Red meat consumption was positively associated with pancreatic cancer risk in men (RR=1.29; 95% CI=1.08-1.53; P(heterogeneity)=0.28; five studies), but not in women (RR=0.93; 95% CI=0.74-1.16; P(heterogeneity)=0.21; six studies). The RR of pancreatic cancer for a 50 g per day increase in processed meat consumption was 1.19 (95% CI=1.04-1.36; P(heterogeneity)=0.46). CONCLUSION: Findings from this meta-analysis indicate that processed meat consumption is positively associated with pancreatic cancer risk. Red meat consumption was associated with an increased risk of pancreatic cancer in men. Further prospective studies are needed to confirm these findings.

Diabetes mellitus and incidence of kidney cancer: a meta-analysis of cohort studies.

AIMS/HYPOTHESIS: Diabetes is associated with increased risk of cancer at several sites, but its association with cancer of the kidney is unclear. We performed a systematic review with meta-analysis to examine the association between diabetes and incidence of kidney cancer. METHODS: Pertinent studies were identified by searching PubMed (from January 1966 to December 2010) and reviewing the reference lists of relevant articles. We included cohort studies reporting RR estimates and 95% CI (or data to calculate them) of the association between diabetes and kidney cancer incidence. Summary RRs were calculated using a random-effects model. RESULTS: Nine cohort studies met the inclusion criteria. Analysis of all studies showed that compared with individuals without diabetes, patients with diabetes had a statistically significant increased risk of kidney cancer (RR 1.42, 95% CI 1.06-1.91). There was heterogeneity among studies (p < 0.001 for heterogeneity). The association was stronger in women (RR 1.70, 95% CI 1.47-1.97) than in men (RR 1.26, 95% CI 1.06-1.49). When restricting the analysis to studies that had adjusted for body mass index (n = 3) or cigarette smoking (n = 3), the RRs were 1.12 (95% CI 0.99-1.27) and 1.29 (95% CI 1.05-1.58), respectively. CONCLUSIONS/INTERPRETATION: This meta-analysis indicates a positive association between diabetes and risk of kidney cancer. Future research should attempt to establish whether this association is causal.

Dietary fiber and fiber-rich food intake in relation to risk of stroke in male smokers.

BACKGROUND/OBJECTIVES: There is convincing evidence that a high dietary fiber intake may lower the risk of coronary heart disease. However, the role of fiber in the prevention of stroke is unclear. We examined the associations of dietary fiber and fiber-rich food intake with risk of stroke within the Alpha-tocopherol, Beta-carotene Cancer Prevention Study. SUBJECTS/METHODS: Between 1985 and 1988, 26,556 Finnish male smokers aged 50-69 years, who had no history of stroke, completed a dietary questionnaire. During a mean follow-up of 13.6 years, 2702 cerebral infarctions, 383 intracerebral hemorrhages and 196 subarachnoid hemorrhages were ascertained. RESULTS: After adjustment for cardiovascular risk factors and folate and magnesium intakes, there was no significant association between intake of total fiber, water-soluble fiber, water-insoluble fiber, or fiber derived from fruit or cereal sources and risk of any stroke subtype. Vegetable fiber intake, as well as the consumption of fruit, vegetables and cereals, was inversely associated with the risk of cerebral infarction; the multivariate relative risks for the highest quintile of intake as compared with the lowest were 0.86 (95% confidence interval (CI): 0.76-0.99) for vegetable fiber, 0.82 (95% CI: 0.73-0.93) for fruit, 0.75 (95% CI: 0.66-0.85) for vegetables and 0.87 (95% CI: 0.74-1.03) for cereals. Vegetable consumption was inversely associated with risk of subarachnoid hemorrhage (relative risk for highest versus lowest quintile: 0.62; 95% CI: 0.40-0.98), and cereal consumption was inversely associated with risk of intracerebral hemorrhage (relative risk: 0.64; 95% CI: 0.41-1.01). CONCLUSIONS: These findings suggest a beneficial effect of the consumption of fruits, vegetables and cereals on stroke risk.

Overweight, obesity and risk of liver cancer: a meta-analysis of cohort studies.

Cohort studies of excess body weight and risk of liver cancer were identified for a meta-analysis by searching MEDLINE and EMBASE databases from 1966 to June 2007 and the reference lists of retrieved articles. Results from individual studies were combined using a random-effects model. We identified 11 cohort studies, of which seven on overweight (with a total of 5037 cases) and 10 on obesity (with 6042 cases) were suitable for meta-analysis. Compared with persons of normal weight, the summary relative risks of liver cancer were 1.17 (95% confidence interval (CI): 1.02-1.34) for those who were overweight and 1.89 (95% CI: 1.51-2.36) for those who were obese. This meta-analysis finds that excess body weight is associated with an increased risk of liver cancer.

Magnesium intake and risk of type 2 diabetes: a meta-analysis.

OBJECTIVE: To assess the association between magnesium intake and risk of type 2 diabetes. DESIGN: Meta-analysis of prospective cohort studies. DATA SOURCES: We retrieved studies published in any language by systematically searching MEDLINE from 1966 to February 2007 and by manually examining the references of the original articles. STUDY SELECTION: We included prospective cohort studies reporting relative risks with 95% confidence intervals for the association between magnesium intake and incidence of type 2 diabetes. RESULTS: The seven identified cohort studies of magnesium intake [from foods only (n = 4) or from foods and supplements combined (n = 3)] and incidence of type 2 diabetes included 286,668 participants and 10,912 cases. All but one study found an inverse relation between magnesium intake and risk of type 2 diabetes, and in four studies the association was statistically significant. The overall relative risk for a 100 mg day(-1) increase in magnesium intake was 0.85 (95% CI, 0.79-0.92). Results were similar for intake of dietary magnesium (RR, 0.86; 95% CI, 0.77-0.95) and total magnesium (RR, 0.83; 95% CI, 0.77-0.89). There was no evidence of publication bias (P = 0.99). CONCLUSIONS: Magnesium intake was inversely associated with incidence of type 2 diabetes. This finding suggests that increased consumption of magnesium-rich foods such as whole grains, beans, nuts, and green leafy vegetables may reduce the risk of type 2 diabetes.

Obesity and the risk of gallbladder cancer: a meta-analysis.

We performed a meta-analysis of studies of the association between excess body weight and risk of gallbladder cancer identified from MEDLINE and EMBASE databases from 1966 to February 2007 and the references of retrieved articles. A random-effects model was used to combine results from eight cohort studies and three case-control studies, with a total of 3288 cases. Compared with individuals of 'normal weight', the summary relative risk of gallbladder cancer for those who were overweight or obese was 1.15 (95% CI, 1.01-1.30) and 1.66 (95% CI, 1.47-1.88) respectively. The association with obesity was stronger for women (relative risk, 1.88; 95% CI, 1.66-2.13) than for men (relative risk, 1.35; 95% CI, 1.09-1.68). There was no statistically significant heterogeneity among the results of individual studies. This meta-analysis confirms the association between excess body weight and risk of gallbladder cancer.

Diabetes mellitus and risk of bladder cancer: a meta-analysis.

AIMS/HYPOTHESIS: Epidemiological evidence indicates that individuals with diabetes mellitus have an increased risk of several cancers. We performed a systematic review with meta-analysis to evaluate the association between diabetes and risk of bladder cancer. METHODS: Pertinent studies were identified by searching MEDLINE (from January 1966 to July 2006) and by reviewing the reference lists of retrieved articles. We included case-control and cohort studies reporting relative risk (RR) estimates with 95% CIs (or data to calculate them) of bladder cancer associated with diabetes. Studies of type 1 diabetes were not included. Summary RRs were calculated using a random-effects model. RESULTS: A total of 16 studies (seven case-control studies, three cohort studies and six cohort studies of diabetic patients) fulfilled the inclusion criteria. Analysis of all studies showed that diabetes was associated with an increased risk of bladder cancer, compared with no diabetes (RR = 1.24, 95% CI 1.08-1.42). There was strong evidence of heterogeneity among these studies (p < 0.0001). Stratification by study design found that diabetes was associated with an increased risk of bladder cancer in case-control studies (RR = 1.37, 95% CI 1.04-1.80, p (heterogeneity) = 0.005) and cohort studies (RR = 1.43, 95% CI 1.18-1.74, p (heterogeneity) = 0.17), but not in cohort studies of diabetic patients (RR = 1.01, 95% CI 0.91-1.12, p (heterogeneity) = 0.35). CONCLUSIONS/INTERPRETATION: Findings from this meta-analysis suggest that individuals with diabetes may have a modestly increased risk of bladder cancer.

Long-term aspirin use and colorectal cancer risk: a cohort study in Sweden.

In a prospective cohort study of 74 250 Swedish women and men, with 7.2 years of follow-up and 705 incident colorectal cancer cases, long duration of aspirin use (>20 years) was associated with a reduced risk of colorectal cancer (multivariate rate ratio: 0.65; 95% confidence interval: 0.45-0.94). Aspirin use for a shorter period was not associated with risk.