© Springer-Verlag London 2015
Vinod H. Nargund, Derek Raghavan and Howard M. Sandler (eds.)Urological Oncology10.1007/978-0-85729-482-1_1010. Diet and GU Cancers
(1)
Department of Urology, Homerton University Hospital NHS Trust, Homerton Row, London, E9 6SR, UK
Keywords
GU cancerDietNutritionCalorieAntioxidantTrace elementsVitaminsCarcinogenicComplementary and alternative medicine (CAM)The Role of Diet in Cancer
Apart from hereditary cancers, most of the malignant tumours are related to the dietary and various environmental factors. Based on the statistical and epidemiological data, Doll and Peto [1] reported that 10–70 % (average 35 %) of human cancer mortality was attributable to the dietary factors. In another study, nearly 35 % of worldwide deaths were attributable to potentially modifiable risk factors with 31 % deaths in high-income countries and 69 % in low and middle-income nations [2]. In this study, the main risk factors for death in low and middle-income countries included smoking, alcohol use, low fruit and vegetable intake while in the high-income countries the main risk factors were smoking, excessive alcohol use, obesity and overweight.
From the initial observations that the oesophageal cancers were more common in people with a high consumption of smoked fish and the link between smoking and lung cancer, it has become obvious that there exists a link between the food we consume and our susceptibility to the development of certain types of cancers. Similarly there has been much written in the popular press about complementary and alternative medicine (CAM) for cancers, including the role of trace elements and anti-oxidants that may actually have a role in prevention of certain types of cancers. The reason as to why this may be the case is the subject of ongoing research. In this chapter we explore the pro and anti carcinogenic effects of food on reducing the risk of developing urological cancer. Cancer patients want to avoid any factors that might have caused their cancer and are also becoming increasingly keen in modulating their diet and embrace alternative/complementary health regimes. However, understanding the precise actions of dietary factors in cancer prevention is not an easy science and any recommendation that is made has to be a qualified one.
Another important question is whether isolated vitamin, mineral and antioxidant supplements are as effective as those naturally present in fruits and vegetables. There are increasing reports that the interaction of the natural vitamins and antioxidants make them more effective than the isolated compounds. Thus there has been an increased public awareness of the benefits of eating fresh fruits and vegetables to prevent or hinder cancer progression rather than just taking proprietary makes of multivitamins and other trace elements. There is compelling evidence of a wide range of dietary factors stimulating or inhibiting the development, growth and spread of tumours in experimental animals.
As mentioned before, there is also a marked difference in the total cancer burden between developed (high income) and developing (low to middle income) countries. The main reason for this variation is probably related to the environmental and lifestyle factors rather than genetic factors [3]. Other factors such as obesity and physical activity have been extensively investigated. Dietary habits coupled with sedentary life style influence the proportion of body fat present in an individual with excessive fat leading to obesity. Its relationship with cancer is being currently investigated in several studies. Renal carcinoma seems to be associated with excess weight (see below) [4].
Prostate Cancer (PCa)
Prostate cancer is the most commonly diagnosed malignancy in men in industrialised countries and the second leading cause of male cancer-related death. It is thus of great importance that any factor that may lead us to decrease the risk of developing or progressing of prostate cancer be explored.
Fat Intake
A close correlation exists between the average per capita fat intake and prostate cancer mortality in numerous countries around the world. Japanese and Chinese men who migrate to the USA experience dramatic increases in prostate cancer risk within one generation compared with their Caucasian neighbours and with the members of their racial group who have retained traditional diet in their homeland [5]. It is also noteworthy that there has been an increase in prostate cancer among Asians in Singapore and Hong Kong who have adopted a western lifestyle, including diet. Also, mortality rates for prostate cancer significantly increased by 3.2 % per year from 1958 to 1993 in Japan as a result of nutrition transition [6]. The Physician’s Health Study by Gann et al. [7] found an association between red meat consumption and prostate cancer risk, but this association was not found to be statistically significant. Linoleic acid, which is the major polyunsaturated fat in most diets, has been associated with an increased risk of prostate carcinoma in some studies. There was no obvious association between prostate cancer and alcohol consumption [8] even at higher doses [9]. In a large multicentre prospective study in Europe [10], there was no evidence of any association between high intake of dietary fat and increased risk of prostate cancer.
Calorie Intake
Few studies investigating the relationship between the risk of developing prostate cancer to calorie intake in rats, have indicated a reduction in tumour growth with energy restricted diet, regardless of the food contents. Thus a reduction in energy intake not just fat seems to be needed to reduce prostate cancer growth in experimental models [11–13]. Overall the emphasis is on control of weight, regular physical activity and avoiding excessive calories.
Meat Mutagenicity in PCa
Meats cooked at high temperatures release carcinogenic heterocyclic amines and polycyclic aromatic hydrocarbons. Koutras et al. [14] observed in their study among 23,080 men with complete dietary data that there was no association between meat type or specific cooking method and risk of developing PCa. However, intake of very well cooked meat was associated with 1.26-fold increased risk of prostate cancer and 1.97-fold increased risk of advanced disease. Although the epidemiological evidence is not consistent, high meat consumption particularly red meat and processed meat has a higher association with increased prostate cancer risk [15].
Agents That May Protect Against PCa
A plethora of epidemiological and some molecular data supports the use of selenium, zinc, vitamin E, vitamin D, lycopene, and green tea as potential preventatives possibly by reducing the oxidative damage in prostatic tissue [16, 17]. Long-term supplementation with α-tocopherol, a form of vitamin E, significantly reduced prostate cancer incidence and mortality in smokers [18]. Some of these agents are being tested in a new large-scale phase III clinical trials.
Selenium: There is a considerable interest in the mineral selenium as a chemopreventative agent in PCa. Selenoproteins- glutathione peroxidase and theoredoxin have antioxidant activity and also affect on DNA methylation. A long term randomised study, known as SELECT (Selenium and Vitamin E Cancer Prevention Trial) evaluated vitamin E and Selenium [19]. It identified the dose for selenium as 200 mcg/day and Vitamin E (reduced dose to prevent the possible cardiovascular effects of higher doses) to 150 IU/day. However, the trial was recently discontinued due to no evidence of benefit from either agent [20].
Green tea: It is a commonly consumed beverage in Asia and its bioactive components include catechins, epigallocatechin-3-galate (EGCG) and theaflavins with catechins being present in high concentration [21]. In vitro investigations have shown that EGCG has protective effects against hormone–related cancers (such as breast and prostate). It is shown to induce apoptosis and affect expression of cell cycle regulatory proteins that are necessary for cell survival and apoptosis [22]. In vitro effects also include its key role in DNA methylation. The effects of polyphenon E (green tea) in prostate cancer patients are interesting [23]. The study was done in a small cohort of men undergoing radical prostatectomy. The findings indicated a significant reduction in serum levels of PSA, HGF, and VEGF after a brief treatment with polyphenon E with no elevation of liver enzymes. These findings support a potential role for polyphenon E in the treatment or prevention of prostate cancer nevertheless these findings have to be corroborated with clinical trials [23]. Although findings of low bioavailability and/or bioaccumulation of green tea polyphenols in prostate tissue and statistically insignificant changes in systemic and tissue biomarkers suggest that prostate cancer preventive activity of green tea polyphenols, if occurring, may be through indirect means and/or that the activity may need to be evaluated with longer intervention durations and repeated dosing [24].
Omega-3 fatty acids, obtained mainly from fatty fish, have been shown to inhibit prostate cancer cell lines in laboratory experiments. The Netherlands Cohort Study found a potential protective effect of omega-3 fatty acids but this was not statistically significant [25, 26].
Soy isoflavins and phytoestrogens: Various epidemiological studies have indicated that consumption of soy containing foods may be associated with a reduction in PCa risk in men. In a metanalysis of 15 epidemiological publications on soy consumption and prostate cancer risk, Yan and Spitznagel [27] concluded that consumption of soy food is associated with a reduction in prostate cancer risk in men. This protection depends on type and quantity of soy products consumed. The ability of soy isoflavins to combine with α and β oestrogen receptors and altering its metabolism is attributed to the isoflavin called genistein [28]. Again the effect seems to be on DNA methylation by moderating the activity of DNA methyl transferase (DNMT). A large-scale cross-national study in 59 countries showed that soy food products were significantly protective (P < 0.001), with an effect size per kilocalorie at least four times as large as that of any other dietary factor [29].
Bladder Cancer
Pro-carcinogenic Factors in Diet
The evidence linking dietary factors and the development of bladder cancer is not quite strong. Environmental toxins (such as used in dye, rubber, and textile manufacturing) seem to predominate as the major factors affecting the incidence of bladder cancers and have been estimated to be responsible for up to 20 % of bladder cancer cases. Aromatic amines from occupational exposures are activated and detoxified through the same reactions that aromatic amines in cigarette smoke are activated and detoxified.
It also means that exposures to occupational agents and cigarette smoke may be additive. In clinical practice, more than 80 % of patients with bladder cancer have a significant smoking history.
Some studies have indicated an increased risk of bladder cancer and coffee drinking [30–32], although this association remains controversial. The role of alcohol in increasing the risk of prostate, renal and bladder cancer is still uncertain, because of the confounding variables of smoking and dietary fat. The exact role of fat intake in bladder cancer is unclear [33]. The high levels of arachidonic acid and its derivatives in meat products, is postulated to have a promoting effect on prostate cancer in animals and the same mechanism may be true in human bladder cancer [34, 35]. Several studies have reported correlation between total fluid intake and the risk of developing bladder cancer [36] but no significant trend was observed [37–39].
Anticarcinogenic Factors in Diet
A reduction in the risk of bladder cancer was observed in nonsmokers with a high intake of cruciferous vegetables (Cabbage, Brussels sprouts, broccoli, and cauliflower) [33]. Protective effects of cruciferous vegetables may be due to their high concentration of the carotenoids, lutein and zeaxanthin. In vitro studies have shown isoflavonoids, found in soy to inhibit bladder cancer cells [33]. The trace element selenium does not possess a proven protection. However, it has been shown that persons with a high selenium plasma level have relatively lower incidence of bladder cancer. The preventive action of nonsteroidal anti-inflammatory drugs (NSAIDs) is controversial. Surprisingly, analgesic users have a lower incidence of bladder cancer [40].
There are no significant data supportive of an independent relationship between the intake of milk or dairy products and the risk of bladder cancer [41], but there are studies suggestive that milk may be related to reduction of bladder cancer risk [42]. The role of various micronutrients including vitamin E, carotenoids, vitamin D, thiamin and niacin in relation to the risk of developing bladder cancer warrants further large scale studies particularly in relation to high risk groups such as heavy smokers and older individuals [43].
Renal Cancer
Investigations have shown an increase in RCC among men and women with high-energy intake [44]. There seems to be he increased risk of RCC with high-energy intake, especially when derived from increased fried meat consumption [44, 45]. Polycyclic aromatic hydrocarbons (PAHs) in barbecued meat, is associated with a higher risk of RCC [46]. Chow et al. [47] reported that high protein consumption was associated with noncancerous chronic renal diseases that may predispose to RCC while other studies did not. Increased consumption of chlorination by-products also appears to increase the risk [48, 49]. Ljungberg et al. [50] showed smoking, overweight and obesity to be established risk factors for RCC. Their study also reported that hypertension and advanced kidney disease, which makes dialysis necessary, also increase RCC risk.
Alcohol consumption seems to have a protective effect for reasons yet unknown. There are not enough data available for many other factors such as salt that may have an important role in the causation of RCC. Recurrent urinary tract infections, increased intake protein and fried foods as well as female sex appear to increase the risk of renal cancer. Thus, dietary modification and other public health measures directed at environmental carcinogens have a potential to reduce the incidence of urological malignancies [51]. In a large prospective diet and health study conducted in the US on nearly half million participants on dietary intake and food sources of fibre in relation to RCC risk over a mean period of 9 years, Daniel et al. found a 15–20 % reduced risk of RCC [52]. Their findings suggested an inverses association between fibre intake and RCC and this was consistent among participants who never smoked, had no history of diabetes or hypertension and had a body mass index of <30 [52].
Nutritional Effects of Anticancer Treatments
Radiotherapy
Most of the side effects of radiotherapy are felt around the second or third week of the treatment and subside 3–4 weeks after the completion of radiotherapy. Chronic side effects appear after a period of long duration of many years [53].
Nearly 70 % of patients receiving radiotherapy to the pelvis experience acute gastro-intestinal symptoms as healthy bowels are inevitably included in the radiation field. Fifty percent of these patients go on to develop chronic bowel symptoms subsequently, which may severely affect the quality of life [54]. It is, therefore, important to give this information to the patients before and after the treatment. There is no evidence base for the use of nutritional interventions to prevent or manage bowel symptoms attributable to radiotherapy. Diarrhoea is treated by high liquid intake and reduction in fibre content of the diet. It is also important to take diet rich in potassium. Low-fat diets, probiotic supplementation and elemental diet merit further investigation. One year after pelvic radiotherapy, dietary manipulation was found to be generally unhelpful for gastrointestinal symptoms, although the role of eliminating raw vegetables is questionable and may benefit from further evaluation. With regard to late effects patients with abnormal body mass index and current smokers are more likely to experience worse symptoms at 1 year [55].
Chemotherapy
Systemic chemotherapy leads to more severe side effects than radiation or surgical treatment. Most side effects are of short duration and subside once the treatment has been discontinued. The main areas that are affected by chemotherapy are those where cell division and growth is rapid, such as oral mucosa, the gastro-intestinal tract, skin, hair and bone marrow. Anorexia, altered taste sensation, nausea, vomiting, stomatitis, mucositis/oesophagitis, diarrhoea and constipation are some well-known side effects. Patients tend to seek for ‘complementary’ therapy to alleviate the side effects of chemotherapy so further research in this direction is necessary. One of the interesting topics is the role of anti-oxidant therapy and its impact on short and long term benefits of chemotherapy and their side effects. This again needs further elucidation [56].
Nutritional Needs of Cancer Patients Who Are Undergoing Active Treatment
The nutritional needs of cancer patients are likely to differ from healthy population in many ways due to hypermetabolism, impaired organ function, increased loss of nutrients, chemotherapy side effects and complications of cancer therapy (surgery, radiotherapy or chemotherapy) [57]. In addition they may also have pre-existing conditions (e.g. chronic renal failure with RCC). Malnutrition in cancer patients is associated with a poor prognosis, history of weight loss being an important predictor of mortality. Malignant disease and its treatments have a major impact on the nutritional status. By improving the nutritional status, there is possibility of improving the prognosis, quality of life and functional status, thereby facilitating improved tolerance to treatment [58]. Dietary counselling is recommended for patients who are at the risk of malnutrition. It should be introduced early in close collaboration with the patient. Administering oral nutritional supplements to malnourished patients has been shown to affect mortality, complications and the length of hospital stay. Supplementation with enteral nutrition has shown to increase appetite, energy intake, nutritional status and, above all, reduced gastrointestinal toxicity from cancer treatments due to a better response to therapy. Supplementation with home parenteral nutrition in terminally ill patients has shown improved quality of life, energy balance, body composition and prolonged survival. These patients usually have less side effects, better wound healing, fewer infections, and are able to be more active. In order to prevent malnutrition from the cancer itself and chemotherapy it is essential that patients are educated about nutritional needs.
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