Risk of bladder cancer by disease severity in relation to metabolic factors and smoking: A prospective pooled cohort study of 800,000 men and women

Abstract

Previous studies on metabolic factors and bladder cancer (BC) risk have shown inconsistent results and have commonly not investigated associations separately by sex, smoking, and tumor invasiveness. Among 811,633 participants in six European cohorts, we investigated sex-specific associations between body mass index (BMI), mid-blood pressure (BP, [systolic + diastolic]/2), plasma glucose, triglycerides, total cholesterol and risk of BC overall, non-muscle invasive BC (NMIBC) and muscle invasive BC (MIBC). Among men, we additionally assessed additive interactions between metabolic factors and smoking on BC risk. During follow-up, 2,983 men and 754 women were diagnosed with BC. Among men, triglycerides and BP were positively associated with BC risk overall (hazard ratio [HR] per standard deviation [SD]: 1.17 [95% confidence interval (CI) 1.06-1.27] and 1.09 [1.02-1.17], respectively), and among women, BMI was inversely associated with risk (HR: 0.90 [0.82-0.99]). The associations for BMI and BP differed between men and women (p ≤ 0.005). Among men, BMI, cholesterol and triglycerides were positively associated with risk for NMIBC (HRs: 1.09 [95% CI 1.01-1.18], 1.14 [1.02-1.25], and 1.30 [1.12-1.48] respectively), and BP was positively associated with MIBC (HR: 1.23 [1.02-1.49]). Among women, glucose was positively associated with MIBC (HR: 1.99 [1.04-3.81]). Apart from cholesterol, HRs for metabolic factors did not significantly differ between MIBC and NMIBC, and there were no interactions between smoking and metabolic factors on BC. Our study supports an involvement of metabolic aberrations in BC risk. Whilst some associations were significant only in certain sub-groups, there were generally no significant differences in associations by smoking or tumor invasiveness.

Serum level and single-nucleotide polymorphisms of toll-like receptor-7 among urinary bladder cancer Iraqi patients

“…Cigarette-smoking is also a further well-established risk factor for UBC worldwide [15]. Interestingly, smoker-men were reported to have UBC more frequently than smoker-women, and accordingly, cigarette-smoking and male gender have been regarded as co-risk factors for UBC [16]. Emerging data suggest that nicotine exposure may enhance tumor growth and metastasis, and there is a growing body of evidence depicting that nicotine promotes cell proliferation, angiogenesis, and epithelial-to-mesenchymal transition through nicotinic acetylcholine receptors found in the urinary bladder, leading to enhanced tumor growth and metastasis [17].…”

Blood pressure and bladder cancer risk in men by use of survival analysis and in interaction with NAT2 genotype, and by Mendelian randomization analysis

“…The exclusion of women in the main analysis was due to very weak statistical power owing to only 182 incident BCs among women in the MDCS and 129 in the UK-biobank. Furthermore, findings from the largest prospective studies indicated no association among women [5,7]. A description of the baseline characteristics among women is shown in the supplementary material (S1 Table).…”

“…Other observational studies of BP and BC risk have shown conflicting results, with some studies showing a positive association [5][6][7][8], and others showing no association [2,[9][10][11], altogether resulting in null results in a meta-analysis that included studies predating our previous study [9]. However, most included studies were hampered by limited sample size and a combined analysis of men and women, who could have different risk profiles as indicated by the results in our study [5] and by the substantially higher BC incidence among men than among women [5,12]. Further, factors interacting with BP in relation to BC might also have caused inconsistent results between studies.…”

“…Regarding bladder cancer (BC), studies in human experimental biology have speculated that the angiotensin-renin system, a physiologic pathway responsible for the regulation of BP, may be involved in BC carcinogenesis [3,4]. We recently reported epidemiologic support of this hypothesis in a large prospective study that showed a positive association between BP and BC risk, but only among men [5]. Other observational studies of BP and BC risk have shown conflicting results, with some studies showing a positive association [5][6][7][8], and others showing no association [2,[9][10][11], altogether resulting in null results in a meta-analysis that included studies predating our previous study [9].…”

The Emerging Landscape of Epidemiological Research Based on Biobanks Linked to Electronic Health Records: Existing Resources, Analytic Challenges and Potential Opportunities

“…Other studies use biobank data to perform epidemiologic analyses using available EHR and/or supplemental survey data. 32,53,[62][63][64][65][66][67][68][69][70][71]54,[72][73][74][75][55][56][57][58][59][60][61] We group these papers published using biobank data into two coarse categories: genetic and non-genetic analyses. Two examples of non-genetic analyses include Song et al (2018), which describes the protective nature of alcohol consumption on coronary artery disease risk in the Million Veterans Program, and Peters et al (2018), which describes sex differences in the association between measures of general and central adiposity and risk of myocardial infarction in the UKB.…”