Introduction:
The most commonly seen type of bladder cancer in the U.S. is transitional cell carcinoma. Risk factors of developing bladder cancer include smoking, chronic urinary tract infection, chemotherapy such as Cytoxan (cyclophosphamide), radiation therapy, and exposure to chemical carcinogens. Chemicals linked to increased risk of bladder cancer include pesticides, aluminum, leather, and rubber.
Meat consumption and bladder cancer:
Bladder cancer in meat eaters, vs. fish eaters vs. vegetarian diet: A 12-year study investigated the relationship between diet and risk of certain cancers. Researchers followed 61,566 British men and women, which included 32,403 meat eaters, 8,562 non-meat eaters who ate fish but not meat (the “fish eaters”) and 20,601 vegetarians (ate neither fish nor meat). Over the follow-up period there were 3,350 incident cancers, including 2,204 among the meat eaters, 317 among the fish eaters and 829 among the vegetarians. In this study, cancer among meat eaters was 3.8%, among fish-eaters, 0.5%, and among vegetarians, 1.3%. The study found that compared to meat-eaters, vegetarians had a 53% reduced risk of bladder cancer. Looking at all cancers combined, vegetarians were 12 per cent less likely to develop cancer than meat eaters, while fish eaters were 18 per cent less likely to develop cancer. (1)
Preservatives in meat and bladder cancer: Nitrites, preservatives used in meat to combat botulism (a form of food poisoning), combine with amines naturally present in meat to form carcinogenic N-nitroso compounds. These compounds have been associated with not only the bladder, but also cancer of the oral cavity, esophagus, stomach and brain. (2)
It has long been suspected that red meat contributed to cancer risk in patients. According to a study conducted between 1983 and 1996 on patients with a red meat intake of at least 7 times per week, the incidence of cancer of the bladder was higher. Therefore, it suggested that the reduction of red meat in the diet might lower the risk of bladder cancer. (3)
Red meat consumption has been found to be associated with various forms of cancer in a multisite case-control study of 11 cancer treatment sites in Uruguay. High consumption of red meat was associated with an increased cancer risk of the bladder (OR= 2.11) and kidney (OR= 2.72). (4)
Vegetables, fruit intake, and bladder cancer:
Broccoli intake and bladder cancer:
The intake of raw cruciferous vegetables has been associated with the reduced risk of bladder cancer. In a study of 239 bladder cancer patients with an average of 8 years of follow-up, it was noted that there was a strong significant inverse association between bladder cancer mortality and the amount of broccoli intake. The intake of broccoli may improve bladder cancer survival. (5)
In a study provided by AgResearch Limited, freeze dried aqueous extract of broccoli sprouts was given to rats after the bladder was exposed to nitrosamine. Nitrosamines are known carcinogens which form after consuming nitrate preservatives. The broccoli sprouts were found to inhibit bladder cancer development. Adding broccoli sprouts to one\’s diet offers important protectants against oxidants and carcinogens. Enzymes contained in broccoli sprouts were rapidly delivered to the bladder after they were consumed through urinary excretion. Therefore, they may be a potential agent for bladder cancer prevention. (6)
Fruit intake and bladder cancer:
A meta-analysis was done of multiple case-control and cohort studies looking at intake of fruits or vegetables and compared this to cancer risk. Researchers analyzed studies between 1973 and 2001. A large number of studies assessed the results for different cancer sites individually. There was a significant reduction in risk for esophageal, lung, stomach and colorectal cancers found with both fruit and vegetable consumption. There was a reduced risk of bladder cancer seen with fruit consumption but not vegetables. The estimates of relative risk from the cohort studies suggested a protective effect of fruits and vegetables for many types of cancers. (7)
High dose vitamins and bladder cancer:
In a double-blind study, high doses of vitamins A, B6, C, and E plus zinc reduced the long-term recurrence of bladder cancer by 40% in patients receiving intravesical (administered directly to the bladder through a catheter) bacillus Calmette-Guerin (BCG) immunotherapy. A total of 65 patients with biopsy confirmed cancer of the bladder participated. One group received high doses of vitamins A (40,000 units), B6 (100 mg), C (2000 mg), E (400 units), zinc (90 mg), and their recommended daily allowance (RDA) for multi-vitamins with BCG therapy. The other group received an RDA multi-vitamin with BCG therapy. At 5 years, the overall recurrence was 24 of 30 patients (80%) in the RDA arm and 14 of 35 (40%) in the high dose arm. (8)
Curcumin (Turmeric) and bladder cancer:
A phase I clinical trial was performed with curcumin as a chemopreventive agent in 25 patients with high-risk or pre-malignant lesions in different organs. The subjects took curcumin once in the morning on an empty stomach at an initial dose of 500 mg/day. The patients were then moved up into the next dose level (1000, 2000, 4000, 8000, and 12,000 mg/day). However, it was not possible to increase patients to the next level (12,000 mg/day) because the bulky volume of the tablets was unacceptable. Tissue samples were taken from the indicator lesions before and at completion of the 3-month treatment with curcumin. The authors found that curcumin was not well absorbed from the GI tract. The peak serum concentration was only 1.77 micromoles even at the 8000-mg/day dose. Results indicate that 25% of patients with uterine cervical intraepithelial neoplasm (CIN) and about 14% of patients with oral leucoplakia developed malignancies in spite of curcumin treatment. Improvement was seen in pre-cancerous lesions in 1 out of 2 patients with recently resected bladder cancer, 2 out of 7 patients of oral leucoplakia, 1 out of 6 patients of intestinal metaplasia of the stomach, 1 out of 4 patients with CIN and 2 out of 6 patients with Bowen\’s disease (squamous cell carcinoma in situ). No toxicity was observed up to 8000 mg/day. (9)
Artificial sweeteners and bladder cancer:
Saccharin, aspartame, acesulfame, and bladder cancer: A study entitled, “Artificial sweetener consumption and urinary tract tumors in Cordoba, Argentina,” compared artificial sweetener use with occurrence of urinary tract tumors. Individuals reported on a questionaire how long they have been consuming the artificial sweeteners saccharin, aspartame, and acesulfame. According to the study, in those with urinary tract tumors, 59% had been consuming artificial sweeteners for a period of greater than or equal to 10 years versus 37% in a group of controls without bladder cancer. This reveals a higher association of urinary tract tumors with consumption of artificial sweeteners longer than 10 years. A drawback of the study was that the 3 artificial sweeteners; saccharin, aspartame, and acesulfame were grouped together together when subjects reported consumption of these sweeteners. Also, the study found that urinary tract tumors were associated with a longer duration of smoking. (10)
Saccharin and urinary tract tumors: Studies have shown that rats developed urinary tract tumors with saccharin but this was not demonstrated in mice, hamsters, or monkeys. There was also no clear evidence of saccharin causing cancer in humans. (11)
Assessment and Plan: Bladder Cancer
- Avoid smoking, seek definitive treatment for chronic urinary tract infection, avoid chemotherapy such as Cytoxan (cyclophosphamide) if possible, avoid radiation exposure whenever possible, and avoid exposure to chemical carcinogens such as pesticides, aluminum, leather, and rubber.
- Consumption of meat, especially red meat and meat containing nitrate or nitrite preservatives was associated with a higher incidence of bladder cancer (and other cancers).
- Vegetarian diet and fish consumption was associated with a lower bladder cancer risk than meat eaters.
- The intake of raw cruciferous vegetables including broccoli may improve bladder cancer survival.
- Broccoli sprouts inhibited bladder cancer development in mice after exposure to nitrosamines.
- Nitrosamines are known carcinogens which form after consuming nitrate preservatives.
- There was a reduced risk of bladder cancer seen with fruit consumption but not vegetables in one study but the types of fruits responsible for this benefit was not defined.
- There is not enough evidence to support the use of curcumin for bladder cancer prevention or treatment and may not be safe especially with a dose escalation seen in the study.
- Artificial sweeteners may increase risk of bladder cancer in humans but there is inadequate evidence to be conclusive.
- Please see the topic: “cancer prevention in general” for additional information.
References:
1.T J Key, P N Appleby, E A Spencer, R C Travis, N E Allen, M Thorogood and J I Mann. Cancer incidence in British vegetarians. Br J Cancer. 2009 Jun 16. http://www.ncbi.nlm.nih.gov/pubmed/19536095
2.Preston-Martin S, Pogoda JM, Mueller BA, Holly EA, Lijinsky W, Davis RL. Maternal consumption of cured meats and vitamins in relation to paediatric brain tumours. Cancer Epidemiol. Biomark. Prev. 1996; 5: 599-605. http://www.ncbi.nlm.nih.gov/pubmed/8824361
3.“Red meat intake and cancer risk: a study in Italy.” Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy. Int J Caner. 2000 May 1;86(3):425-8. http://www.ncbi.nlm.nih.gov/pubmed/10760833
4.Aune D, et al. Meat consumption and cancer risk: a case-control study in Uruguay. Asian Pac J Cancer Prev. (2009). http://www.ncbi.nlm.nih.gov/pubmed/19640186
5.“Intake of cruciferous vegetables modifies bladder cancer survival.” Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Carlton House Rm 365, Buffalo, NY 14263, USA. Cancer Epidemiol Biomarkers Prev. 2010 Jul;19(7):1806-11. Epub 2010 Jun 15. http://www.ncbi.nlm.nih.gov/pubmed/20551305
6.“Inhibition of urinary bladder carcinogenesis by broccoli sprouts.” AgResearch Limited, Ruakura Agricultural Research Center, Hamilton, New Zealand. Cancer Res. 2008 Mar 1;68(5):1593-600. Epub 2008 Feb 29. http://www.ncbi.nlm.nih.gov/pubmed/18310317
7.Riboli E, Norat T. Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk. Am J Clin Nutr. 2003 Sep;78(3 Suppl):559S-569S. http://www.ncbi.nlm.nih.gov/pubmed/12936950
8.Lamm DL, Riggs DR, Shriver JS, vanGilder PF, Rach JF, DeHaven JI. Megadose vitamins in bladder cancer: a double-blind clinical trial. J Urol 1994 Jan;151(1):21-6. http://www.ncbi.nlm.nih.gov/pubmed/8254816
9.Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 2001 Jul-Aug;21(4B):2895-900. http://www.ncbi.nlm.nih.gov/pubmed/11712783
10.Andreatta MM, Muñoz SE, Lantieri MJ, Eynard AR, Navarro A., Prev Med 2008 Jul;47(1):136-9. Epub 2008 Apr 8. http://www.ncbi.nlm.nih.gov/pubmed/18495230
11.Ellwein LB, Cohen SM. The health risks of saccharin revisited.Crit Rev Toxicol. 1990;20(5):311-26. http://www.ncbi.nlm.nih.gov/pubmed/2202324
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