Genetics (family history and ageing)

Most cancers are sporadic and have no strong hereditary basis. A large number of cancers have now been found to have a genetic link, but this is not the key factor leading to the development of the cancer.⁶ Genetic cancer research is being very actively researched with the hope of detecting those individuals who are at risk, and then being able to provide additional protection through lifestyle changes. Hopefully in the future, it may be possible to genetically engineer these genes with the aim of preventing cancer.

A number of cancers are recognised as syndromes of cancer that have a defective tumour suppressor allele.⁷ The following are examples: mutations in genes, BRCA1 and BRCA2 which are associated with an elevated risk of breast and ovarian cancers, and hereditary non-polyposis colorectal cancer (HNPCC), also known as the Lynch syndrome. Several genes are involved and include cancers of the colorectum, uterine, gastric and ovarian sites without preponderance of colorectal polyps. A range of genetic mutations and switches are activated which can initiate cancer.

Behavioural and social factors

Psycho-oncology is the scientific field that describes the links between psychological and social factors with cancer. Depression is the key emotional factor that can influence immunity (psychoneuroimmunology (PNI)), as well as numerous hormones (psychoneuroendocrinology (PNE)). Depression can also influence lifestyle factors, including smoking, excess alcohol, physical activity and excess weight.⁸

The general overview of the key mechanisms involved in cancer are shown in Figure 9.1

Figure 9.1 Mind–body medicine connections

An extensive review by David Spiegel concluded that chronic and severe depression is probably associated with an increased risk of developing cancer and the evidence was strong that depression predicts a poor prognosis, with more rapid progression of cancer.⁹ Risk of developing cancer due to depression is nearly doubled, independent of other lifestyle factors, and it is not related to any particular cancer.^{10, 11, 12}

The longer the duration of depression the greater the risk for developing cancer.¹³ Depression and stress depress immunity and also increase levels of cortisol, growth hormone, prolactin and epinephrine, all of which are known to stimulate cancer growth.^14–17

Insulin plus insulin-like growth factors (IGFs) have been shown in numerous epidemiological studies to be involved in increasing cancer risk.^{18, 19, 20} Stress can suppress natural killer cells leading to poor cancer surveillance in some cancers.²¹ There is increasing evidence that behaviour can influence our genes. Stress can damage DNA and impair genetic mutation repair.^{22, 23, 24}

Personality factors, as well as sexual differences, are important relating to DNA damage.²⁵ DNA damage is related to tension, anxiety and self-blame coping strategy in males, and in females, depression and rejection. The worst factor was the lack of subjective closeness to parents in childhood. DNA damage was also higher in subjects who had experienced the loss of a close family member within the last 3 years.

Immune cells have less ability to initiate genetically programmed cancer cell suicide with psychological stress.²⁶ The repair of DNA is often depressed in cancer patients, which is a possible marker of cancer susceptibility.²⁷

Shift work is associated with an increased risk of cancer which may be due to depleted melatonin levels.²⁷ Melatonin is known to have a positive influence on immunity and also has anti-cancer effects.^{28, 29}

Melatonin can inactivate cancer genes plus inhibits cancer growth factors.³⁰

Inflammation and infection

Chronic inflammation is a central event that is closely associated with cancer development. Under normal circumstances, insulin has an anti-inflammatory action but this can be reversed with insulin resistance.^{31, 32}

A recent study found that people with the highest blood levels of C-reactive protein were about 3 times more likely to develop colorectal cancer, as those with the lowest ranges.³³ Elevated serum interleukin-6, which is another inflammatory marker, is also linked to cancer.³⁴ The interesting chemo-prevention of cancer with COX-2 inhibitors is partially to do with this inflammatory process.^{35, 36, 37}

Selective COX-2 inhibitors (Clecoxib and Rofecoxib) were used to prevent cancer with reasonable success, but withdrawn for this use because of serious side-effects.^{38, 39, 40}

Curcumin, which is found in ginger and turmeric, is a COX-2 inhibitor and also has anti-cancer activity.^{41, 42} It is possible that the anti-inflammatory action of vitamin D is an important reason why it can protect from cancer.^{43, 44, 45} Inflammation associated with surgery can increase the size of metastases.⁴⁶

Men with periodontal disease have been found to have 63% higher risk of pancreatic cancer compared to those with no sign of the disease.⁴⁷ Inflammation is thought to be a key factor, but also higher levels of oral bacteria and higher levels of nitrosamines might also play a role. Other studies have shown that periodontal disease is a risk factor for other cancers.^{48, 49}

Dietary factors

It is now understood that the development of most cancers is clearly a result of an intimate interaction between endogenous and lifestyle factors, the most notable of these lifestyle factors is diet. Estimates suggest that approximately 30% of cancers are a consequence of suboptimal diet.^{74, 75, 76} In developing countries, the contribution of diet to cancer is estimated to be lower (20%) based mainly on higher tobacco consumption.⁷⁷

Our food and drink contain mutagens and carcinogens in addition to a variety of chemicals that may be able to block carcinogenesis.⁷⁸ Epidemiological investigations have been very helpful in defining the general profile of the diet which is protective: one which is low in red meat and various fats, modest in calories and alcohol, and high in fruit, vegetables and fibre. It is quite clear that a diet high in fresh fruits and vegetables is highly protective against colorectal cancer.^{79, 80}

It is important to note that nutrition plays a role in influencing the body in many ways (e.g. immunity, behaviour) and, hence, it is likely that it plays some part in the development of all cancers, even where there is no data available. Most of the data relating to cancer and nutrition is for the more common cancers, and it is likely that a food that is good or bad for 1 cancer will be good or bad for another cancer.

Air pollution

Long-term exposure to combustion-related air pollution is known to increase the risk of lung cancer, being higher in the more polluted cities.⁹⁸ The cancer risks of organic hazardous air pollutants in the US have been ranked.⁹⁹ Most of the polycyclic aromatic hydrocarbon, benzene, acetaldehyde and 1,3-butadiene risk was found to come from outdoor sources, whereas indoor sources were primarily responsible for chloroform, formaldehyde, and naphthalene risks.⁹⁹

Electromagnetic fields (EMFs)

An advisory panel to the US and National Institutes of Science challenged a 1996 panel from the same institutes which said they found no conclusive evidence that EMFs generated by power lines and appliances were a threat to humans.¹⁰⁰

The more recent panel found that children living near power lines appeared to have a 50% risk of leukaemia and adults had a similar increased risk of leukaemia if they were exposed to high levels of EMFs from utilities in their work places.¹⁰⁰

A Tasmanian study has investigated residential exposure to electric transmission lines and risk of cancer.¹⁰¹ This case-controlled study found that there is a possibility that residents close to high voltage power lines, especially early in life, may increase the risk of myeloproliferative and lymphoproliferative disorders. Further larger, independent studies are required to be more conclusive about this issue.

In developed countries, people are constantly being irradiated from numerous sources including phones, internet, wireless, various kitchen appliances (e.g. microwave ovens and electric blankets), and it remains controversial as to whether this exposure produces adverse health effects. It is possible that EMFs may interfere with melatonin secretion.^{102, 103}

A case-controlled study of 1700 workers employed as electricians and exposed to electric fields showed no increase in leukaemia, but there was an increase in brain tumours (no specific type), as well as colorectal cancer.¹⁰⁴

Genetically modified foods (GM foods)

Current research in GM foods is contradictory and inconclusive, and includes much evidence showing potential health risks.¹⁰⁵ Compass cases of adverse reactions to GM crops in humans have been recorded ranging from allergies following skin contact to an outbreak of unprecedented disease affecting thousands and dubbed eoseniamyalgia.^{106, 107}

It is controversial whether GM crops can produce higher yields. There is also evidence showing that non-GM crops using natural matters can increase crop yield.¹⁰⁸ There is insufficient data to do with the long-term effects of GM foods on human health.

Ionising radiation

Most people are unaware that the greatest source of exposure to ionising radiation is background radiation in the environment, which constitutes 82% of all exposure (see Figure 9.2).¹⁰⁹

Figure 9.2 Ionising radiation exposure to the public

(Source: Nasca PC, Pastides H 2008 Fundamentals of Cancer Epidemiology. Jones and Bartlett Publishers, Boston)

Medical radiation is the largest source of human-made radiation and exposure is continuing to increase with time.¹¹⁰ X-ray treatment for ankylosing spondylitis increases the risk of leukaemia, radiation for menorrhagia leads to a threefold risk of leukaemia, and radiotherapy to cancer patients has been clearly shown to increase the risk of developing secondary cancers.^{111, 112, 113} The thyroid is particularly sensitive to ionising radiation, especially when given to children.¹¹⁴

A recent retrospective study found that thyroid cancer patients with exposure to radiation from health care work places, or treatments for conditions such as breast cancer and acne, appeared to have worse outcomes than patients with the disease and no exposure.¹¹⁵ The use of computer tomography (CT) scans is of real concern, as studies demonstrate that radiation exposure from CT coronary angiography is a risk for cancer.¹¹⁶ Melbourne radiologists have called for a curb on CT scans unless completely essential.¹¹⁷

Toxic chemicals

Diesel exhaust fumes in trucking industry workers

Trucking industry workers who have regular exposure to diesel vehicle exhaust and other types of vehicles on highways, city streets, and loading docks have an elevated risk of lung cancer with increasing years of work.¹²²

Exposure to pesticides

Brain tumours have been associated with several occupational and environmental exposures.^{123, 124, 125}

Some pesticides contain alkylureas or amines that metabolise to nitroso compounds which have been associated with neurogenic tumours.¹²⁶ However, a more recent study investigating exposure to pesticides and risk of adult brain tumours did not find an association between herbicide or insecticide exposure among men.¹²³ Women with occupational exposure to herbicides had an increased risk of meningioma.¹²³

Exposure to the styrene-butadiene rubber industry

An epidemiological study of 17 000 workers in the rubber industry found an increased risk of chronic lymphocytic and myelogenous leukaemia in the most highly exposed workers.¹²⁷ Furthermore, in a study of workers involved in butadiene-monomer production, an association with non-Hodgkin’s lymphoma was found.¹²⁸

Ethylene oxide

This chemical is used in the production of other chemicals although most human exposure occurs from its use in sterilisation of medical equipment. An increase in breast cancer occurs with a significant exposure-response relationship between ethylene oxide exposure and breast cancer incidence.¹²⁹

Vinyl chloride exposure

Two large multi-centre cohort studies in facilities that manufactured vinyl chloride, polyvinyl chloride or polyvinyl chloride products showed a substantial increase in the relative risk for liver and gliosarcoma with risk increasing with duration of exposure or total exposure.^{130, 131}

Hair dyes

Personal use of hair dyes may play a role in the risk of follicular lymphoma and chronic lymphatic leukaemia plus small lymphocytic leukaemia.¹³² A meta-analysis of epidemiological data has found that personal use of hair dyes is associated with an increased risk of bladder cancer.¹³³

Cooking oil fumes

Fumes from 6 different oils: safflower, olive, coconut, mustard, vegetable and corn have been collected and polycyclic aromatic hydrocarbons (PAHS) were extracted from air samples.¹³⁴ Fumes from safflower oil, vegetable oil and corn oil were found to have PAHS. It is thought that PAHS fumes are linked to lung cancer.

Risks to fire fighters

A review of 32 studies on fire fighters, which was to determine cancer risk using a meta-analysis, has found that there is an elevated risk of multiple myeloma.¹³⁵ In addition, a probable association with non-Hodgkin’s lymphoma, prostate and testicular cancer was demonstrated.

Cancer prevention

The protective effect of regular exercise has been demonstrated in a number of cancers including breast, colorectal, prostate, testicular and lung cancer.^{145, 146, 147} There is also evidence that exercise may offer protection against endometrial, ovarian and also other forms of cancer.^{145, 148, 149}

Exercise is known to improve immunity in the following ways:

A large study of 30 000 men found that unless they were extremely obese, cardiorespiratory fitness can abolish the risk of dying of cancer associated with being overweight.¹⁵⁷

In the US, the surgeon general recommends 30 minutes a day of exercise most days of the week, which is generally accepted as 5 days of the week for a total of 150 minutes a week.^{158, 159}

Resistance exercise may also be protective, as it can reduce insulin resistance in a similar way to aerobic exercise.^{160, 161}

Cancer survival

Regular exercise can improve survival in colorectal and breast cancer patients, 50–60%.^{162, 163}

A study of 3000 women with various stages of breast cancer were followed for 18 years and those who walked 3–5 hours per week had twice the survival than those who did not exercise.¹⁶³ A further study in women with breast cancer, followed up for a period of 9 years, who exercised regularly had a 44% reduction in mortality.¹⁶⁴ A group of 500 colorectal cancer patients were found to have half the mortality if they exercised regularly.¹⁶²

In a very large prospective study of nearly 48 000 men, of the men over 65 years of age 3000 developed prostate cancer. Those who exercised regularly had reduced their chance of developing an aggressive cancer by two-thirds compared to the men who did not exercise.¹⁶⁵

A meta-analysis of cancer survival following chemotherapy in cancer patients by Morgan and others, found that survival was improved by 2% in 5 years, which is minimal compared to the benefits of exercise.¹⁶⁶

Exercise used during cancer treatment can counteract side-effects of disease and treatments.¹⁶⁷ Twice weekly resistant training appears to be safe and well-tolerated, resulting in increased muscle mass and decreased body fat.¹⁶⁸ Resistance exercise, particularly useful in men receiving androgen deprivation therapy for prostate cancer, resulted in improved quality of life and muscular fitness.¹⁶⁰

Cancer fatigue

Exercise may also reduce fatigue resulting from chemotherapy, in cancer patients. Regular exercise can increase the fitness in breast cancer patients treated with conventional chemotherapy.¹⁶⁹

The relative importance of cancer fatigue has been compared with other patient symptoms and concerns over 9 cancer types, and emerged as the top-rated symptom.¹⁷⁰ To explore this issue, the author surveyed 534 patients and 91 physician experts from 5 institutions and community support agencies. It was thought by most that fatigue was attributable to both disease and treatments. Sleep disorders and difficulty falling asleep, problems maintaining sleep, poor sleep efficacy, early awakening and excessive daytime sleep are prevalent in cancer patients.¹⁷¹ Cancer fatigue can be modified by ensuring optimum sleep quality.¹⁷² Exercise and counselling may help to reduce fatigue.¹⁷³

Breast screening

In Australia the government recommends recruiting and screening women aged 50–69 years for early detection of cancer. Women aged 40–49, and 70 years and older are able to attend for screening.²⁰⁸

There can be differences in the results of screening when comparing different countries. A comparison of screening mammography in the US and the UK found that open surgical biopsy rates are twice as high in the US than in the UK, but the cancer detection rates were similar.²⁰⁹

Efforts to improve US mammographic screening should target lowering the recall rate without reducing the cancer detection rate. Recently MRI has been used to detect breast cancers that cannot be detected by mammography and ultrasonography.²¹⁰

Russian equipment utilising a microwave imaging technique which detects heat at depths of 6cm may be able to detect breast cancer earlier than mammography especially in younger women with dense breasts.^211,212 An advantage of this technology is that is does not involve radiation.

Early diagnosis of breast cancer is associated with better prognosis, especially when implemented with lifestyle improvements, as well as psychosocial change.²¹³

A recent Norwegian study found that it is likely that some breast cancers detected by mammography would not persist to be detectable at the end of 6 years by mammography, raising the possibility that the natural course of some screen-detected invasive breast cancers is to spontaneously regress.²¹⁴

A screening mammography can result in 33% more surgery, 20% more mastectomies and more use of radiotherapy because of over-diagnosis and others argue that the information provided to the patient about screening mammography is incomplete.^{215, 216} Keen and Keen, from the US, found after an extensive analysis, that less than 5% of women with screen-detectable cancers have their lives saved.²¹⁷ Both of these studies are reviewed by a Lancet editorial which points out that there are problems with screening in mammography, and also that there are vested interests that make screening a business.²¹⁸

Cervical screening

Cervical screening is one of the oldest and most successful forms of screening to prevent cancer. The PAP smear can detect both cervical dysplasia and carcinoma, and is now thought that about 80% of high-grade dyskaryosis and high-grade dysplasia will not progress to cancer.²¹⁹

Human papilloma virus (HPV) can cause cervical cancer and the majority of the HPV involved can be eradicated by vaccination against HPV if used before being infected by the virus.²²⁰ There has been concern about the potential effect of decreased cervical cancer screening participation after HPV vaccination.²²¹ Like most other cancers, cervical cancer is strongly associated with lifestyle factors and diet. Risk factors include unsafe sex, smoking (even second-hand smoke), being overweight and an unhealthy diet.²²²

The following nutrient supplements can be protective or prevent dysplasia from progressing:

The role of nutrients and cervical cancer has been summarised by Sali and Vitetta.²²⁴

It is uncertain whether particular nutrients can reduce the rate of acquisition of a high risk HPV or whether they facilitate the clearance of high risk HPV. Women with higher folate blood levels are inversely associated with a positive high risk HPV test when compared to lower folate status.²²⁸ A large case-controlled study has found that serum homocysteine was strongly and significantly predictive of cervical cancer risk.²²⁹

Psychosocial support and mental relaxation

There are a number of modalities that have been found to benefit cancer patients including cognitive behavioural interventions, supportive psychotherapy, informational and educational treatments, social support, as well as exercise therapy, art therapy, music therapy plus other therapies. In general, it is agreed that psychosocial support for cancer patients is therapeutic.^{241 242}

Even chatting, ideally with a confidante, helps in influencing mortality related to cancer. Research shows that 7 years after initial breast cancer treatment, a patient with 1 confidante can improve life expectancy by 15%, whereas 2 confidantes can lead to an improvement of 25%.²⁴³

Various treatment programs have also been established to help cancer patients to cope with the various psychosocial problems that are associated with this disease; programs such as the Gawler Foundation in Melbourne.²⁴⁴

Hypnosis

Breast cancer patients undergoing surgery reported less anxiety and less analgesic if they used hypnosis.²⁵⁹ It is likely that there would be cost reduction in the care of surgical patients who have less pain and less anxiety. Mental wellbeing was also improved with the use of hypnosis in patients undergoing radiotherapy.²⁶⁰

Hypnotherapy has also been beneficial for children being treated with chemotherapy; they have less nausea prior to and after chemotherapy.²⁶¹

Tai chi

Tai chi is a mixture of various physical movements and synchronised breathing with meditation. The physical demands of tai chi need not be great and can be suitable for most cancer patients. A clinical trial on breast cancer patients found that tai chi performed for 60 minutes, 3 times per week, can improve quality of life and self-esteem.²⁶² A recent study has shown that tai chi can improve immunity.²⁶³

Qigong

Qigong is a mind–body integrative exercise, or intervention, from Chinese medicine used to prevent and cure ailments, and to improve health and energy levels through regular practice.²⁶⁴ One study has reported decreased leukopaenia and platelet count, as well as decreased anaemia resulting from chemotherapy in the qigong group.²⁶⁵ Several reviews claim that qigong offers therapeutic benefits for cancer patients.^{266, 267, 268}

Nine studies, 4 randomised and 5 non-randomised, were examined. The methodology was regarded as being poor. Two trials suggested effectiveness in prolonging life of cancer patients. The reviewers concluded that the evidence supporting qigong was incomplete based on the studies that were analysed.²⁶⁵

Another study showed decreased psychological distress with qigong.²⁶⁹

Psychological improvements occurred in an experimental group of participants after 1 month of practicing qigong.²⁷⁰

Reiki and/or therapeutic touch

Reiki is classified as an energy medicine, as is qigong, in the US CAM classification. A number of small clinical studies generally show some benefit in cancer patients in reducing pain and fatigue.

A study on cancer patients has used an evidence-based approach to examine research regarding the effectiveness of therapeutic touch.²⁷¹ This review examined 12 clinical studies involving cancer patients. All studies had experimental control groups. Eleven of the studies reported benefit from therapeutic touch.

Massage therapy

Massage therapy differs to reiki or therapeutic touch, as it involves application of varying degrees of pressure to the body. Benefits of massage in palliative care are found later in this chapter.

Massage can reduce pain in cancer patients.²⁷² It has also been shown to be useful for postoperative pain.²⁷³ Massage was effective in controlling nausea in breast cancer patients.²⁷³

Biofeedback

Biofeedback involves measurement of muscle tension with electrobiography and also temperature or measurement of brain waves (electroencephalography).

It is possible with biofeedback to control processes that are normally voluntary. The measurements are visible on a monitor to the patient. It has been beneficial in treating cancer pain, and also helping to regain both urinary and faecal competence after surgery.²⁷⁴

Music therapy

Music therapy is provided by musicians who also receive training as counsellors. In cancer patients it has been shown to treat anxiety related to radiotherapy.²⁷⁵ Music therapy can also reduce pain plus nausea and vomiting related to chemotherapy.²⁷⁵

Music therapy has been found to be beneficial in the treatment of blood pressure, insomnia, depression, pain and stress in those without cancer.

Aromatherapy

Aromatherapy is discussed later in this chapter under palliative care. A few studies have demonstrated that aromatherapy can reduce stress, pain, depression and also can improve quality of life.^{276, 277, 278}

Carotenoids

Dietary lycopene are carotenoids that are found in tomatoes and other red-coloured foods and has been shown in clinical studies to protect against cancer, including prostate, pancreas, ovary, breast, CRC and bladder cancer.^279–285

Lycopene can inhibit IGF-1 in rat prostate.²⁸⁶ Lycopene supplement can also suppress prostate cancer growth.²³¹

An extensive survey found that 57 of 72 studies reported an inverse association between tomato intake or blood lycopene level and cancer risk.²⁸⁷ Evidence for benefit was strongest for cancers of the prostate, lung and stomach. There was also benefit for pancreas, CRC, oesophagus, oral cavity, breast and cervix.

In addition to preventing cancer, vitamin A derivatives have been used to cure promyelocytic leukaemia.²⁸⁸

Curcumin

Curcumin is an active ingredient in the spice turmeric, and has been shown to prevent cancer and also have therapeutic properties. Curcumin can suppress tumour initiation, promotion and metastases.²⁸⁹

Curcumin can decrease PGE-2 substantially and this may be 1 of its actions in antagonising cancer.²⁹⁰ Curcumin can inhibit in vitro growth of cancers of prostate, colon and animal breast cancer.^{291, 292, 293}

A small study using curcumin in pancreas cancer patients showed improvement in some patients.²⁹⁴ In animal experiments, curcumin circumvents chemo-resistance in vitro and potentiates the effect of Thalidomide and Bortezomib against multiple myeloma.²⁹⁵ Curcumin can inhibit the growth of cancer cells and enhances the anti-tumour effects of Gemcitabine and radiation.²⁹⁶ In another study, curcumin was found to sensitise ovarian and breast cancer cell lines to cisplatin through apoptotic cell death.²⁹⁷

Teas

Teas have protective effect against cancer, but the unfermented green tea offers the best protection with the catechins and theaflavins being the active ingredients.²⁹⁸

Consuming 5 or more cups of green tea a day reduced the risk of developing breast, lung, leukaemia and prostate cancer and could help reduce recurrence in breast and ovarian cancer.^299–303 It is possible that tea may protect from squamous cell skin cancers also.³⁰⁴

In an in vitro study, tea polyphenols plus retinoic acid inhibited cervical cell growth and promoted apoptosis. Polyphenol by itself was inactive.³⁰⁵ A nutrient formulation which includes green tea, lysine, proline, arginine and ascorbic acid inhibits in vitro renal carcinoma growth and invasion.^{306, 307}

A recent study found that hot tea was associated with squamous cell carcinoma of the oesophagus.³⁰⁸ The mechanisms for this are not understood. It is controversial if milk, added to tea, can impair the bioavailability of tea catechins.^{309, 310}

Allium vegetables

Cruciferous vegetables

Cruciferous vegetables include cabbage, cauliflower, broccoli, bok choy, and brussel sprouts. Although a vegetable intake has been shown to be protective against cancer, results can be inconsistent. It is thought that this inconsistency can be explained by specific sub-groups of vegetables such as the cruciferous vegetables which are more strongly related to cancer risk.³¹⁵

In the Health Professional Study (HPFS), cruciferous vegetables were associated with decreased risk of bladder cancer.³¹⁶ These vegetables are also protective for prostate and lung cancer.^{317, 318, 319}

It is possible that these vegetables may decrease breast cancer risk due to the action of indole-3-carbinol which is found in cruciferous vegetables.³²⁰

The 16 alpha-hydroxyestrone plus 4-hydroxyestrone are thought to be responsible for the carcinogenic effect of oestrogen. On the other hand, the oestrogen metabolite 2-hydroxyestrone has been found to be protective against several types of cancer, including breast cancer.³²¹ Indole-3-carbinol can increase the ratio of 2-hydroxyestrone to 16 alpha-hydroxyestrone, and also to inhibit the 4-hydroxalation of oestradiol.³²²

There is controversy whether microwave cooking can destroy active ingredients of the cruciferous vegetables with 1 group finding that it does, and the other finding the opposite.^{323, 324} It is thought that the addition of water to these vegetables at the time of microwaving may be critical.³¹⁹ If cooking does influence the active ingredients in the cruciferous vegetables, this could also explain discrepancy of findings.³²⁵

Mushrooms

Medicinal properties have been attributed to mushrooms for thousands of years. Mushrooms can exert tumour-inhibitory effects by influencing T cells and macrophages, and it is thought that the glucans (lentinans) from mushrooms mediate these effects.³²⁶

Glycoproteins (lectins) present in mushrooms, broad beans, seeds and nuts have been shown in vitro experiments to increase the differentiation of cancer cells indicating that the cancer processes are either halted or reversed, as well as inhibiting cell multiplication.³²⁷ Inhibition of colon cancer and lymphoma by lentinan from shitake mushrooms has also been documented in animal experiments.³²⁸

Another mushroom (Phellinus linteus), has been shown to suppress breast, melanoma and prostate cancer growth, and also angiogenesis. The active substances are thought to be polysaccharides.^{329, 330} The Phellinus linteus mushroom has been found to have a synergistic effect with Doxorubicin and prostate cancer cell lines.³³¹

Anticancer effect of Ganoderma lucidum on in vitro breast cancer cells is increased by green tea extract.³³² A large case-controlled study in China revealed that high dietary intake of mushrooms decreased breast cancer risk in pre- and post-menopausal women, and there was an additional decreased risk of breast cancer from the joint effect of mushrooms and green tea.³³³

In vitro studies demonstrate that both mushrooms and green tea suppress invasive behaviour of cancer cells.³³⁴ Mushroom extracts increase the activity of natural killer cells in gynaecological cancer patients undergoing chemotherapy.³³⁵

Polysaccharide extract of Ganoderma lucidum, when given 1800mg, 3 times daily for 12 weeks improved the natural killer cell numbers in advanced stage cancer patients.³³⁶

Polysaccharide peptides (PSP) isolated from a mushroom Coriolus versicolor significantly improved leukocyte and neutrophil count in a randomised, double-blind, placebo-controlled study of patients with advance non-small cell lung cancer.³³⁷ Another clinical study which included patients with various cancers treated with maitake mushroom showed a significant improvement, especially in those patients with breast, lung and liver cancer.³³⁸

Soy

Epidemiological studies have demonstrated the role of soy in cancer prevention of breast, prostate, endometrium and stomach.^339–342 Soy intake is most protective against breast cancer when consumed during childhood as found in a recent case-controlled study.³³⁴

Early Genistein exposure from soy promotes cell differentiation in breast tissue which suppresses the development of breast cancer in adulthood by decreasing the activity of the epidermal growth signal pathway. It has been observed that soy isoflavone Genistein induces apoptosis and inhibits growth of both androgen sensitive and androgen independent prostate cancer cells in vitro.³⁴³

The isoflavones, Genistein and Diadzein stimulate the synthesis of serum hormone-binding globulin (SHBG) in the liver which results in a fall of testosterone levels.^{344, 345}

Isoflavones can also reduce free androgens.³⁴⁶ A combination of soy phytochemical concentrate in green tea can reduce serum IGF and testosterone concentrations in mice.³⁴⁷ Soy and tea combinations have the potential of preventing breast and prostate cancers.³⁴² Genistein can inhibit colonic cancer cells in vitro.³⁴⁸

Colon cancer can be hormonally influenced.³⁴⁹ A Japanese case-controlled study investigating the association between dietary isoflavone intake and risk of colorectal adenoma revealed a significant inverse association between dietary isoflavone intake and risk of colorectal adenoma.³⁵⁰

Genistein can inhibit human stomach cancer cell growth in vitro.³⁵¹ Genistein has also been shown to inhibit the growth of leukaemia in vitro.³⁵² This finding has led to the development of ipriflavone, a phenyl isoflavone, a derivative used as a treatment of leukaemia.³⁴⁷

Bladder cancer cells are also inhibited in vitro by soy isoflavones.³⁵³ A study from Singapore found an increased risk of bladder cancer linked to dietary soy intake.³⁵⁴ Consideration should be given to the chemical modification of isoflavones in soy foods during cooking and processing.³⁵⁵

Soy isoflavone Genistein in mouse models of melanoma has an anti-tumour and anti-angiogenic activity.³⁵⁶ Similar anti-angiogenic effects were obtained with soy food based diet. Another study found that soybean isoflavones reduced the experimental metastases in mice.³⁵⁷ Genistein has been demonstrated to be a radio-sensitiser for prostate cancer in vitro and animal experiments.³⁵⁸

Citrus fruits

Citrus fruits are thought to offer protection from cancer through their flavonoid content. Their high vitamin C content may also be important.³⁵⁹ The flavonoids can control cancer cells by suppression, blockage and transformation.³⁵⁴ Citrus fruits can have anti-proliferative, anti-invasive and anti-angiogenic effects.³⁵⁴ Citrus flavonoids have anti-proliferative effects on the following cancer cells: squamous, meningioma, leukaemia, breast, lung, melanoma and hepatoma.³⁵⁴

A systematic review has investigated the association between dietary intake of citrus fruits and gastric cancer risk.³⁶⁰ High citrus fruit intake is protective against stomach cancer. Citrus fruits have also been found to have a possible protective effect on bladder cancer.³⁶¹

There is an inverse association between intake of citrus fruits and the risk of pancreatic cancer, and squamous cell oesophageal cancers.^{362, 363}

Folic acid and cancer risk

The association with folic acid and CRC has been previously discussed. Dietary folate deficiency has also been associated with an increased risk of other cancers including prostate, breast, bladder, oral, pharyngeal, ovary, pancreas and lung cancer.^367–373

It is thought that the key role of folate is that it can guard against DNA damage and promote gene stability.³⁷⁴

Pomegranate and ellagic acid

Pomegranate shows both antioxidant and anti-atherosclerotic properties attributed to the high content of polyphenols including ellagic acid in its free and bound forms, gallotamins and anthocyanins and other flavonoids. The most abundant of these polyphenols is punicalagin, a potent antioxidant which is hydralised to ellagic acid.^{375, 376}

Ellagic acid, which is also found in berries and other plant foods, has been shown to exhibit anticarcinogenic properties in vitro and in animal experiments.^{377, 378}

Pomegranate juice was found to have greater anti-proliferative action against human oral, colon and prostate tumour cells compared to purified polyphenols punicalagin and ellagic acid.³⁷⁹ Pomegranate juice has been found to have in vitro and in vivo anti-cancer properties against human breast cancer, human promyelocytic leukaemia cells, lung, liver, oesophageal and pancreas cancer.^{379, 380, 381} Ellagic acid can significantly potentiate the anti-carcinogenic potential of quercetin in vitro human leukaemia cells.³⁸²

A study on humans with rising PSA after surgery or radiotherapy for prostate cancer with a Gleeson score = /< than 7, who were treated with pomegranate juice significantly reduced the rate of PSA increase.³⁸³

Communication problems with medical practitioners

Due to the lack of education of medical practitioners in nutritional medicine, patients are frequently unable to receive relevant nutritional medicine information.³⁹⁶ Patients fear discussing issues relating to supplements because they often receive a negative response from their medical practitioner. There are a number of communication problems between the oncologist and patient. A recent study found that oncologists and thoracic surgeons rarely responded empathically to the concerns raised by patients with lung cancer.³⁹⁷ Empathic responses that did occur were frequently in the last third of the encounter.

Another study has also found that the oncologists encountered a few empathic opportunities and responded with empathic statements infrequently.³⁹⁸

Previous research has shown that the physicians responded to empathic opportunities in 38% of surgical cases, and in 15–21% of primary care cases.^{399, 400}

Empathy is associated with improved patient satisfaction and compliance with recommended treatment.^{390, 401} Patients who are satisfied with their consultation, have improved understanding of their condition with less anxiety, and improved mental functioning.⁴⁰²

Cancer specialists also struggle if they are discussing the high costs of drugs with patients. Surprisingly, the oncologists surveyed reported the least difficulty with disclosing cancer diagnosis and being honest about the patient’s prognosis.⁴⁰³

A study has found that nearly all oncologists disclose to their patients that they will die, although there is a wealth of data concerning advanced-cancer patients who do not understand their prognosis.⁴⁰⁴ Fostering of hope, even in terminally ill patients, is essential.⁴⁰⁵

A cross-sectional nationwide survey was conducted with 714 (56%) members of the Clinical Oncology Society of Australia.⁴⁰⁶ Results show that Australian cancer care workers experience considerable occupational distress and regular screening for burnout is recommended.

Nutritional status of cancer patients

Malnutrition in cancer patients is common and an inverse prognostic indicator of survival with up to 80% of patients with cancer being malnourished on presentation.^{407, 408, 409}

Malnutrition is a significant contributor to death in up to 20% of patients.⁴¹⁰ Those that have lost weight have a poorer response to treatment, reduced quality of life and increased risk of death.^{411, 412} The NICE guidelines state that patients should undergo nutritional assessment.⁴¹³ Unfortunately few doctors deal with malnutrition adequately.^{414, 415}

A UK survey found that 72% of specialist oncological trainees were incapable of identifying patients with malnutrition.⁴¹⁶ A Swedish study also found that doctors had inadequate nutritional knowledge.

Selenium / vitamin E

Selenium supplements can protect from cancer especially with CRC, lung, oesophageal, gastric and prostate cancer.^{417, 418} It is likely that dietary selenium is protective against breast cancer, but other studies have not supported this finding.^{371, 419} Selenium levels decline with age and therefore it is possible that selenium supplementation may be of benefit, in particular in the elderly.³⁷¹ Selenium supplementation does not benefit nor protect basal and squamous cell carcinomas of the skin.⁴²⁰

The result of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) and Vitamins and Lifestyle (VITAL) studies does not support a role for vitamin E, either alone or in combination with selenium for prostate and other cancers.^{421, 422} A series of other studies do not support this finding.^423–429

Reasons for failure of the SELECT study include the use of a vitamin E supplement that reduces gamma-tocopherol which offers major protection against prostate cancer.^{382, 383} The problems of using synthetic forms of vitamin E, as used in this study, have been highlighted previously. It is suggested that future supplement studies should combine alpha and gamma-tocopherol together.³⁸² Selenium can sensitise human prostate cancer cells to TRAIL, a cytotoxic agent indicating that selenium may help overcome resistance to cytotoxic drugs.^{430, 431}

Tamoxifen is widely used for the treatment of oestrogen-sensitive breast cancer, but the subsequent development of resistance is a key problem. Studies on breast cancer lines show that selenium synergises with Tamoxifen to improve its efficacy and help overcome resistance.^{432, 433}

Vitamin E can reduce the risk of developing breast, lung, prostate, gastrointestinal and ovarian cancers.^{434, 435, 436}

Vitamin E supplements may also be able to reduce the risk of breast cancer recurrence among breast cancer survivors.⁴²⁷ Long-term use of vitamin E protected against bladder cancer.⁴³⁷ In animal studies, vitamin E has been shown to be protective against melanoma.⁴³⁸ Vitamin E analogues can induce apoptosis in malignant cell lines and inhibit tumourogenesis in vivo.⁴³⁹ Vitamin E analogues, epitomised by alpha-tocopherol succinate are pro-apoptotic agents with selective neoplastic activity.^{440, 441}

Flavonoids combined with vitamin E can reduce angiogenic peptide vascular endothelial growth factor from human breast cancer cells, and the inhibitory effect was greatest from the flavonoid naringen and alpha-tocopherol succinate.⁴⁴² Another major defect with these negative studies is the lack of an integrative approach which would consider behavioural, dietary, exercise and the importance of vitamin D levels.

Vitamin C

A number of case control studies have investigated the role of vitamin C in cancer prevention, and most have shown that higher intakes of dietary vitamin C are associated with decreased incidence of cancers of the mouth, throat, vocal chords, oesophagus, stomach, CRC and lung.^{443, 444}

Combinations of vitamin C and other micronutrients generally show a positive result. Vitamin C and retinoic acid can inhibit the proliferation of human breast cancer cells by altering their gene expression.⁴⁴⁵

Lipoic acid can synergistically enhance ascorbate cytotoxicity in vitro experiments.⁴⁴⁶

Ascorbate efficacy was also enhanced in an additive fashion with vitamin K₃.⁴³⁷

The dose of micronutrients used in this latter study could be achieved in vivo. Dietary vitamin C, E and beta-carotene have been shown to be protective against uterine cancer in a systematic literature review and meta-analysis.⁴⁴⁷ A case control study also found that dietary vitamin C and E showed an inverse association with prostate cancer incidence.⁴⁴⁸

In the double-blind placebo-controlled Women’s Antioxidant and Cardiovascular Study, women were supplemented with vitamin C, vitamin E (600IU every other day) and beta-carotene 50mg (every other day). Supplements with vitamins C, E and beta-carotene either individually or in combination did not reduce cancer incidence or reduce cancer mortality.⁴⁴⁹

The Males Physicians’ Health Study II was a randomised double-blind placebo-controlled trial of vitamin E, 400IU (every other day) and vitamin C, 500mg daily.⁴⁵⁰

Neither vitamin E nor C supplementation reduced the risk of prostate cancer or total cancer in this large trial.

A large randomised placebo-controlled trial (SELECT) investigated the role of selenium (200mcg/day selenium methionine), and vitamin E (400IU synthetic form). Selenium or vitamin E, alone or in combination, did not prevent prostate cancer.³⁷⁹

In all of these randomised placebo-controlled trials, the alpha-tocopherol form of vitamin E was used. In 2 of the studies, it was the synthetic form of vitamin E, in none of these studies was gamma-tocopherol used which is the predominant form in foods.⁴⁵¹

The doses of the type of vitamin E used in these studies are known to reduce the absorption of the gamma form of vitamin E. In SELECT, gamma-tocopherol was measured and showed nearly a 50% decline.^{452, 453}

Gamma-tocopherol form of vitamin E is the most protective against prostate cancer.⁴⁴⁵ Hence the lowering of gamma-tocopherol in SELECT is likely to have been a factor in the lack of cancer risk reduction. In the Physicians’ Health Study, synthetic form of vitamin E was used; the natural form has proven to be better.⁴⁵⁴

When Japanese researchers gave natural and synthetic vitamin E and measured blood levels, 100mg (149IU) of natural vitamin E produced levels that required 300mg (448IU) of synthetic vitamin E to achieve.⁴⁵⁵

Most studies show that the synthetic vitamin E is only half as active in the body as the natural form.⁴⁵⁶ The doses of vitamin E used in all of these studies are inadequate and also the incorrect form is being used. It is unknown if a higher dose of vitamin C may be more protective. Vitamin C is a water-soluble vitamin, and it is more possible to maintain elevated serum levels if it is taken at least twice daily. It is not consistent with an integrative approach towards cancer prevention to be relying on 1 or 2 supplements.

The integrative approach involves stress reduction, relaxation techniques, regular exercise, healthy food with adequate sunlight exposure plus the use of supplements to support healthy lifestyle and diets. Integrative doctors seldom use single or double nutrients as they are used in clinical studies.

Vitamin D

Vitamin D plays a role in the prevention of numerous cancers including breast, CRC, prostate, pancreas, ovary, skin, non-Hodgkin’s lymphoma and other sites.^464–467

It is also known that those that live near the equator have higher vitamin D levels and are less likely to die from cancer than people in northern latitudes.⁴⁶⁸

Data from the Third National Health and Nutrition Examination Survey in the US showed that serum vitamin D deficiency exists in the US and it has major public health implications.⁴⁶⁹ Studies relating to vitamin D and cancer have been inconsistent, but researchers agree that deficiency should be prevented and vitamin D supplemented as necessary depending on blood levels.⁴⁷⁰

There is also some evidence showing that cancer survival is linked to vitamin D levels. A large study in England found that cancer survival was dependant on season of diagnosis and sunlight exposure with diagnosis in summer and autumn associated with improved survival compared to that in winter.⁴⁷¹

Other studies have shown that exposure to sunlight was associated with reduced mortality from breast, ovarian, prostate, colon and lung cancers.^{466, 472, 473} Further evidence is warranted to examine the link between vitamin D and cancer incidence, survival and mortality.

Multivitamin use and risk of cancer

The role of multivitamins in isolation from an integrative approach remains controversial. In 2002, JAMA published a review supporting the role of vitamin use, especially as there are groups of patients who are at higher risk for vitamin deficiency and suboptimal vitamin status.⁴⁷⁴ Another review came to the conclusion that multivitamin and mineral supplement use may prevent cancer in individuals with poor or suboptimal nutritional status.⁴⁷⁵ It is suspected that common micronutrient deficiencies are likely to damage DNA which is likely to be a major factor in cancer development.^{476, 477}

A Women’s Health Initiative study collected data on multivitamin use at baseline and follow-up time for a 7.9 year period.⁴⁷⁸ This study showed that multivitamin use had little or no influence on the risk of common cancers. Criticism of this study include that it was not a prospective placebo-controlled double-blind study which could avoid bias, little detail is given about the composition of the multivitamin, and there was no verification of dose taken or if the supplement was taken at all.

Individuals who used dietary supplements generally report higher dietary nutrient intakes and healthier diets, and also have healthier lifestyles.^{479, 480, 481}

Antioxidants and cisplatin

Cisplatin can be used effectively in the treatment of solid tumours, utilising free radical damage, but unfortunately it has a number of undesirable side-effects including neurotoxicity leading to deafness and peripheral neuropathy and nephrotoxicity.

The use of nutritional and herbal antioxidants with cisplatin in human and animal experiments reduces side-effects and increase efficacy of treatment in some studies.^504–508

Foods and hormonal influence

The enormous diversity of foods available, theoretically, can influence tumour growth or influence hormonal treatments. Foods with high flavonoid content (e.g. vegetables, fruit, cocoa, red wine) and herbs such as St John’s wort and St Mary’s thistle may have theoretical positive effects.⁵⁰⁹

The role of soy in breast cancer patients who are hormone positive is conflicting, but it is likely to enhance the antagonism of oestrogen-binding agents such as Tamoxifen.⁵¹⁰

Integrative approach

If a patient is to use nutritional or herbal supplements then a clinician with expertise in these supplements should be involved during concurrent chemotherapy and radiotherapy, as it is not only about providing a supplement, but caring for the patient with an integrative approach.

Does lifestyle and diet influence recurrence?

A number of studies have shown that lifestyle and diet influence longevity, and hence, it would be reasonable to assume that they would also influence survival in cancer patients. Several studies have found that the Mediterranean lifestyle and diet helps to prevent cancer and illness in general, as well as a reduction in cancer and overall mortality.^517–519

Major scientific associations strongly encourage people to consume a Mediterranean-style dietary pattern to reduce their risk of disease.^{517, 518, 519} Studies show that a healthier diet and lifestyle can reduce the risk of mortality of cardiovascular disease and cancer.^520–522

A number of recent studies have found that diet and lifestyle factors influence survival of cancer patients. A study was established to see whether a telephone counselling and mailed print material-based diet and exercise intervention was effective in reorientating functional decline in older, overweight cancer survivors.⁵²³

Long-term survivors of colorectal, breast, and prostate cancer found diet and exercise intervention reduced the rate of self-reported functional decline compared with no intervention.

Pre–treatment health behaviours which included smoking, diet and physical activity predict survival among patients with head and neck squamous cell carcinoma.⁵²⁴

A systematic review of the effect of diet on prostate cancer prevention and treatment found that dietary recommendations for patients diagnosed with prostate cancer was similar to those aiming to reduce the risk of prostate cancer.⁵²⁵

A multi–centred prospective study investigating the interaction between physical activity, diet and obesity to breast cancer survival has concluded that those who consume a healthy diet and are physically active may increase their years of survival after diagnosis.⁵²⁶ They further stated that the combination of these 2 variables appears to attenuate the increased risk of cancer death observed among obese cancer survivors.

A report describing longitudinal changes in lifestyle behaviours and death status among colon cancer survivors and population-based controls, examined demographic and psychosocial correlates of healthy lifestyle changes following a colon cancer diagnosis.⁵²⁷

Colon cancer survivors reported significant increases in vegetable intake, physical activity and supplement use, and a non-statistically significant increase in fruit/fruit juice consumption. The pre-diagnosis of patients undergoing potentially curative colorectal cancer surgery influenced 5-year survival.

Another study investigated the association of dietary patterns with cancer recurrences and mortality of colon cancer survivors.⁵²⁸ During a median follow-up of 5.3 years, a higher intake of a Western dietary pattern was associated with a higher risk of recurrence and mortality among patients with stage 3 colon cancer treated with surgery and adjuvant chemotherapy.

It is surprising that a meta-analysis of 59 trials published earlier found little evidence that diet is associated with survival or prognosis of cancer patients.⁵²⁹ In an accompanying editorial examining the study it is suggested that errors in study design may have led to the wrong conclusions.⁵³⁰

Herbal medicines

Plant products have been used for centuries as medicine. In the developing world, plant remedies are the most common treatments. Many oncology drugs are derived from plant products; for example, Taxol and Taxotere from the Western yew tree (Taxus brevifolia).⁵³¹

Although examples of traditional usage of herbal medicines are available, there have been limited, more organised clinical studies. In traditional Chinese medicine, multiple herbs are generally used and hence it is difficult to understand the role of individual herbs. In traditional use of these herbs, other factors are also likely to be important, such as positive support by practitioners and dietary changes.

There are many herbal medicines that have been investigated regarding their role against cancer. It is only possible to include some examples of these herbs in this chapter.

Chinese herbal medicines

There are numerous Chinese herbs that have potential for the use in the treatment of cancer. A number of controlled clinical studies have reported responses to numerous cancers when treated by various herbal therapies. Some of the larger studies are seen in Table 9.3.

A Cochrane review of medicinal herbs for oesophageal cancer was performed to assess the benefit of Chinese herbal medicines by comparing chemotherapy or radiotherapy with or without concurrent medicines.⁶⁰⁵ This review found that there were no RCTs in the field and, hence, they were not able to make any recommendations. Another Cochrane review investigated the role of Chinese medicinal herbs in the treatment of side-effects of chemotherapy in breast cancer patients.⁶¹⁰ Seven randomised studies were identified involving 542 patients using various herbs. The results suggested that Chinese herbal medicine improved marrow suppression, the immune system and may improve quality of life. There was no evidence of toxicity from Chinese herbal medicine. However, there were concerns about the quality of trials and that they were unable to draw any conclusions.

The role of Chinese medical herbs for chemotherapy side-effects in colorectal cancer patients have also been the subject of a Cochrane review.⁶⁰²

Four relevant studies which included 442 patients were found to have adequate data. It was concluded that decoctions of Huang Qi compounds provided some benefit compared to patients that were treated with chemotherapy alone. Patients receiving the Huang Qi decoctions were less likely to experience nausea and vomiting, plus white cell counts increased and there is also some evidence of immune stimulation. No toxicity was found from the Huang Qi decoctions. The reviewers suggest further large scale trials with Huang Qi decoctions and the prevention of chemotherapy-related side-effects.⁶⁰²

Acupuncture

There is no scientific evidence that acupuncture is effective in the treatment of cancer itself. Beta-endorphins and neuropeptides are increased with acupuncture, which increases interleukin-2 (IL-2) levels and natural killer cell activity. It is possible that these changes could have a positive influence on prognosis of some cancers.⁶²³

Based on systematic reviews, acupuncture and acupressure reduce chemotherapy nausea-induced symptoms.^{624, 625, 626}

The role of acupuncture for control of cancer pain remains controversial. A systematic review of 6 clinical trials did not show an advantage over ‘sham’ acupuncture.⁶²⁷

A recent systematic review of RCTs of acupuncture, placebo acupuncture and no acupuncture was unable to conclude about the role of acupuncture and whether pain was reduced because of the treatment ritual. There is now evidence that ‘sham’ acupuncture has a significant placebo effect.⁶²⁸ The role of acupuncture in the treatment of hot flushes in breast cancer patients is controversial.^{629, 630} It is possible that acupuncture may be useful in reducing flushing symptoms in prostate cancer patients on hormone therapy.⁶³¹

Acupuncture was useful in the treatment of cancer-related fatigue after chemotherapy in a preliminary study.⁶³² A study has also found that it can help with xerostomia resulting from radiotherapy.⁶³³

Safety of integrative medicine in cancer patients

There is concern about the interaction of nutritional and herbal supplements with drugs, and hence the importance of being aware of what drugs and supplements the patient is taking.

Drug-to-drug interactions are far more likely to be a problem, but it is possible to have interactions with nutritional and herbal supplements. Acupuncture generally has a very good safety record with the most frequent complications being only minor, such as bleeding and/or bruising and minor pain.⁶⁵⁹