Modifiable risk factors for the prevention of bladder cancer: a systematic review of meta-analyses

Abstract

Each year, 430,000 people are diagnosed with bladder cancer. Due to the high recurrence rate of the disease, primary prevention is paramount. Therefore, we reviewed all meta-analyses on modifiable risk factors of primary bladder cancer. PubMed, Embase and Cochrane database were systematically searched for meta-analyses on modifiable risk factors published between 1995 and 2015. When appropriate, meta-analyses (MA) were combined in meta–meta-analysis (MMA). If not, the most comprehensive MA was selected based on the number of primary studies included. Probability of causation was calculated for individual factors and a subset of lifestyle factors combined. Of 1496 articles identified, 5 were combined in MMA and 21 were most comprehensive on a single risk factor. Statistically significant associations were found for current (RR 3.14) or former (RR 1.83) cigarette smoking, pipe (RR 1.9) or cigar (RR 2.3) smoking, antioxidant supplementation (RR 1.52), obesity (RR 1.10), higher physical activity levels (RR 0.86), higher body levels of selenium (RR 0.61) and vitamin D (RR 0.75), and higher intakes of: processed meat (RR 1.22), vitamin A (RR 0.82), vitamin E (RR 0.82), folate (RR 0.84), fruit (RR 0.77), vegetables (RR 0.83), citrus fruit (RR 0.85), and cruciferous vegetables (RR 0.84). Finally, three occupations with the highest risk were tobacco workers (RR 1.72), dye workers (RR 1.58), and chimney sweeps (RR 1.53). The probability of causation for individual factors ranged from 4 to 68 %. The combined probability of causation was 81.8 %. Modification of lifestyle and occupational exposures can considerably reduce the bladder cancer burden. While smoking remains one of the key risk factors, also several diet-related and occupational factors are very relevant.

Epidemiology of Bladder Cancer

“…A recent meta-analysis found that among bladder cancer cases studied, between 1995 and 2015, 81.8% could be attributed to known preventable causes. Only 7% of bladder cancer cases are predicted to arise from heritable genetic influence [9]. With such a large proportion of cases attributable to known environmental causes, bladder cancer is an optimal candidate for public health prevention interventions.…”

“…A diet rich in fruits and vegetables may help prevent bladder cancer, though the extent to which remains controversial. An analysis of several meta-analyses found that higher intake of selenium, Vitamins A, D and E, and folate were all associated with a reduction in bladder cancer incidence [9]. Vitamin E is an anti-inflammatory and antioxidant which may counter damage caused by free radicals.…”

“…In fact, approximately 80% of cases of bladder cancer are diagnosed in adults age 65 or older, reflecting a disease course that requires decades of exposure or develops decades after exposure [4]. Heritable genetic predispositions have also been implicated in approximately 7% of bladder cancer cases [9].…”

STOP smoking and alcohol drinking before OPeration for bladder cancer (the STOP-OP study), perioperative smoking and alcohol cessation intervention in relation to radical cystectomy: study protocol for a randomised controlled trial

“…Smoking is also the major and most modifiable risk factor for development of bladder cancer in both men and women [7]. …”

Antioxidants and selenocompounds inhibit 3,5-dimethylaminophenol toxicity to human urothelial cells

“…If not counteracted by antioxidants and intracellular antioxidant systems, ROS damages important cellular molecules, including proteins, lipids, and DNA (15). Low antioxidant levels, low selenium in particular, increase the risk of several types of malignancies, including bladder cancer (16,17). Selenium is a component of several antioxidant enzymes, namely glutathione peroxidases (GPx) and thioredoxin reductases (TrxR) (18,19).…”