Prostate cancer

Prostate cancer is the most common cancer in men in the UK, with over 40,000 new cases diagnosed every year (NHS Choices, 2012g). It is the second most common cause of cancer death in UK men, after lung cancer (Cancer Research UK, 2012b). In the UK, about one in nine men will get prostate cancer at some point in their lives. This lifetime risk includes men who get prostate cancer at any age and more than half of all cases are diagnosed in men over 70, prostate cancer is quite rare in men under 50 (Cancer Research UK, 2012c).

Prostate cancer develops from cells within the prostate gland which is the size of a walnut and lies directly under the bladder. The prostate produces a protein called prostate-specific antigen (PSA) which turns semen into liquid form. The majority of prostate cancers are slow growing and it may be some time before any symptoms are noticed, which can make this disease less treatable. Symptoms include: needing to urinate often, especially at night; difficulty starting to urinate; straining to urinate or taking a long time to finish and pain when urinating or during sex. Other less common symptoms include: pain in the lower back and blood in the urine.

Cancer is not usually inherited, but some types (breast, ovarian and prostate cancer) can be influenced by genes and can run in families. Having a close male relative (such as a brother, father or uncle) who has had prostate cancer can be linked to an increased risk. Men who have relatives with breast cancer (especially under the age of 60) may also have a higher risk of prostate cancer. This increased risk may be caused by inherited faulty genes BRCA1 and BRCA2. Men who carry a faulty BRCA1 gene may have a slightly higher risk (one per cent) of male breast cancer. Some studies suggest there may be a slight increase in the risk of prostate cancer. Men who carry a faulty BRCA2 gene have a seven per cent higher chance of getting breast cancer and a 20-25 per cent higher lifetime risk of developing prostate cancer. Most of these prostate cancers occur over the age of 45 (Oxford University Hospitals NHS Trust, 2011).

There are many different factors that influence the development of prostate cancer Experts think that just five to 15 per cent of prostate cancers are linked to inherited genes (Macmillan Cancer Support, 2013a). That means that 85 per cent or more of prostate cancers are caused by environmental and/or lifestyle factors. Research suggests there may be a link between obesity and prostate cancer and that men who regularly exercise have a lower risk of developing the disease. Some evidence suggests that diet can affect your risk of developing prostate cancer. Current thinking suggests that a diet high in animal fats may increase your risk of developing prostate cancer. In particular, red meat (such as beef, lamb and pork), eggs and dairy produce (including butter, whole milk, cheese and cream) contain a lot of saturated fat (Macmillan Cancer Support, 2013a). As we see with other hormone-dependent cancers (for example, breast cancer), the highest incidence rates of prostate cancer occur in the developed world and the lowest rates are seen in Africa and Asia. However, African-American men are more affected than white American men. This suggests that prostate cancer risk is influenced by dietary and lifestyle factors.

Figure 6.0 shows how the incidence of prostate cancer varies widely around the world. Incidence rates are highest in Australia, New Zealand and Western Europe (104 and 93 per 100,000 in 2008 respectively), where prostate cancer screening and PSA testing is common. The lowest rates are seen in South-Central Asia; four per 100,000 (Cancer Research UK, 2012d).

Research shows that prostate cancer rates are lower in countries with low consumption rates of typical Western foods such as meat and dairy. However, advice from the NHS on the links between diet and prostate cancer is fairly sparse. They say that there is evidence that a diet high in calcium is linked to an increased risk of developing prostate cancer and that some research has shown prostate cancer rates appear lower in men who eat foods containing certain nutrients including lycopene, found in tomatoes and other red fruit, and selenium, found in Brazil nuts (NHS Choices, 2012h).

It is now well-documented that diets high in calcium and dairy protein can increase the risk of prostate cancer (Cancer Research UK, 2012c). One of the earliest reports linking dairy consumption to prostate cancer was published in the 1980s when a study of over 27,000 Californian Seventh-Day Adventists who had completed dietary questionnaires 20 years earlier concluded that milk consumption was positively associated with prostate cancer mortality (Snowdon, 1988). Since then many more reports have confirmed an increased risk from the consumption of dairy foods.

One possible mechanism for the action of milk in increasing prostate cancer risk may involve the calcium in milk. Researchers from Harvard Medical School have shown that high consumption of calcium is linked to advanced prostate cancer (Giovannucci et al., 1998). It has been suggested that calcium increases prostate cancer risk by suppressing circulating vitamin D (Giovannucci, 1998). In a study of 3,612 men observed between 1982 and 1992, 131 prostate cancer cases were identified and dietary intake analysed (Tseng et al., 2005). Results confirmed that dietary calcium was associated with an increased risk whereas vitamin D was not associated. The researchers concluded that dairy consumption may increase prostate cancer risk through a calcium-related pathway.

More recently an EPIC study found that a 35g per day increase in consumption of dairy protein was associated with a 32 per cent increase in the risk of prostate cancer. They also found that calcium from dairy products was positively associated with risk, but not calcium from other foods. These results support the hypothesis that a high intake of protein or calcium from dairy products may increase the risk for prostate cancer (Allen et al., 2008). Given that calcium and low-fat milk are vigorously promoted to reduce risk of osteoporosis (and colon cancer), the mechanisms by which dairy and calcium might increase prostate cancer risk should be clarified and confirmed (Tseng et al., 2005).

Another study considered the oestrogen content of milk as a causal factor, having noted that the typical Western diet (characterised by milk and meat products) contains higher levels of oestrogen than the foods eaten by Asian men who suffer much less from prostate cancer. This study measured the hormone contents of two kinds of commercial milks (from Holstein and Jersey cows) and found that levels were markedly higher than they were 20 years ago. This was attributed to modern dairy farming methods whereby around 75 per cent of commercial milk comes from pregnant cows (Qin et al., 2004).

In a more recent study looking at the effects of persistent milk consumption beyond weaning (adults drinking milk) it was stated that epidemiological evidence points to increased dairy protein consumption as a major dietary risk factor for the development of prostate cancer. This study reported how bioactive molecules in cow’s milk initiate a signalling pathway (protein-mediated mTORC1 signalling) and that this, along with constant exposure to commercial cow’s milk oestrogens derived from pregnant cows, may explain the observed association between high dairy consumption and increased risk of prostate cancer in Westernised societies. Normally, only infants consume milk up until weaning, so milk-mediated mTORC1 signalling is restricted to the postnatal growth phase of the vast majority of mammals – this is the natural state. Only milk proteins (compared to meat and fish) have the unique ability to preferentially increase both the insulin/IGF-1 and leucine signalling pathways necessary for maximal mTORC1 activation. In other words, the persistent consumption of cow’s milk in humans provides a unique combination of factors that can lead to prostate cancer. The author suggests that a contemporary Palaeolithic diet and restriction of dairy protein intake may offer protection from the most common dairy-promoted cancer in men of Western societies (Melnik et al., 2012).

Numerous studies now indicate that the growth factor IGF-1 is associated with an increased risk of prostate cancer. In an early Swedish study, levels of IGF-1 were measured in blood samples from over 800 men, 281 of whom were later diagnosed as having prostate cancer. A strong correlation between IGF-1 and prostate cancer was observed and it was concluded that circulating IGF-1 levels are associated with an increased risk for this disease (Stattin et al., 2004). In a pooled reanalysis of worldwide prospective data based on 3,700 men with prostate cancer and 5,200 controls, researchers also concluded that high circulating IGF-1 concentrations are associated with a moderately increased risk for prostate cancer (Roddam et al., 2008).

In 2007, an EPIC study (based on 630 cases and 630 controls), found a marginally increased prostate cancer risk for men with the highest IGF-1 levels (Allen et al., 2007). In an extension of this work (this time based on 1,542 prostate cancer cases matched to 1,542 controls) IGF-1 concentration was significantly associated with an increased risk of prostate cancer. It was concluded that these results suggest that circulating concentrations of IGF-1 in middle to late adulthood are strongly associated with subsequent prostate cancer risk over the relatively long term (Price et al., 2012). Campbell suggests that IGF-1 is turning out to be a predictor of certain cancers, including prostate cancer, in much the same way that cholesterol is a predictor of heart disease (Campbell and Campbell, 2005).

As stated previously the diet can influence IGF-1 levels in the blood and dairy products have been shown to increase the level of circulating IGF-1 (Young et al., 2012). In a group of healthy, middle-aged men, dairy products, milk and calcium were all associated with raised IGF-1 levels (Gunnell et al., 2003). In the same study, high intakes of vegetables and tomatoes, or tomato-containing products, were associated with lower levels of IGF-1. Furthermore, a study published in the British Journal of Cancer noted that vegan men had a nine per cent lower serum IGF-1 level than meat-eaters and vegetarians (Allen et al., 2000). So again it is shown that milk increases IGF-1 and raised IGF-1 is linked to increased risk of cancer.

Research has clearly established that IGF-1 has a very important role in the development and progression of certain cancers, including prostate (Meinbach and Lokeshwar, 2006). Recent prospective epidemiological studies have also consistently shown strong associations between circulating IGF-1 levels and the subsequent risk of developing prostate cancer (Roddam et al., 2008). Individuals with circulating IGF-1 levels at the upper end of the normal range are at significantly increased risk of subsequently developing prostate cancer years later.

Perhaps of greater significance though is the fact that recent evidence from population studies of prostate cancer suggests that the association with IGF-1 is not so much of an effect on cancer initiation,but reflects an effect on the risk of progression to clinically relevant disease (Holly 2013a). As mitogens (substances that encourage cell division), and antiapoptotic agents (substances that prevent apoptosis or cell death) IGF-1 may be important in carcinogenesis, possibly by increasing the risk of cellular transformation by enhancing cell turnover (Kucuk et al., 2001). In other words, many men develop prostate cancer (or benign tumours) but IGF-1 may transform the tumours into a more aggressive form of cancer (Holly et al., 2013a). Either way, IGF-1, from cow’s milk, appears to be a risk factor that could easily be avoided by eliminating dairy foods from the diet.

It has been suggested that men with prostate cancer who increase consumption of plant-based foods and avoid dairy products and meat may significantly increase their chances of survival. Researchers from the Physicians Committee for Responsible Medicine (PCRM) reviewed eight observational studies and 17 intervention studies on the effect of a plant-based diet on prostate cancer results and found that a plant-based diet may slow prostate cancer progression and improve prognosis (Berkow et al., 2007). They found that diets high in saturated fat are associated with a threefold higher risk of cancer progression and death, compared with a diet low in saturated fat. In addition, specific plant foods, including flaxseeds and lycopene-rich tomatoes, may help slow prostate cancer progression.

Possible mechanisms of action for lycopene, the major carotenoid in tomatoes, include the following:

  • inhibition of growth in cancer cells by modulating the expression of cell cycle regulatory proteins
  • modulation of the IGF-1/IGFBP-3 system (IGF signalling is thought to affect tissue growth and development with IGF-1 and IGF binding protein-3 (IGFBP-3) having putative pro- and anticarcinogenic properties respectively)
  • up-regulation of tumor suppressor proteins and increased gap junctional intercellular communication
  • modulation of redox signaling
  • prevention of oxidative DNA damage
  • modulation of carcinogen metabolising enzymes

Source: Kucuk et al., 2001.

While the precise molecular mechanisms underlying the development of prostate cancer are still being teased out, the effects of changing the diet have produced positive results. Researchers at the Preventative Medicine Research Institute in California evaluated the effects of dietary changes in 93 volunteers who had chosen not to undergo conventional treatment for early prostate cancer. This was a unique opportunity to observe the effects of diet and lifestyle changes without the confounding effects of radiation or surgery. Participants in the lifestyle-change group were placed on a vegan diet consisting primarily of fruits, vegetables, whole grains and pulses supplemented with soya, vitamins and minerals. Two standard tests were used to assess disease status. The first was a routine blood test measuring PSA levels; this protein produced by the prostate gland can be used to assess disease progression. The second test relied on differences in the growth rates of a human prostate cancer cells (LNCaP) treated with patient serum. This is a standard laboratory test used for evaluating the effects of conventional treatments of prostate cancer.

While none of the experimental (vegan) patients underwent conventional treatment during the study, six control patients underwent treatment due to an increase in PSA and/or progression of the disease on magnetic resonance imaging. PSA decreased four per cent in the experimental group but increased six per cent in the control group. Although the magnitude of these changes was relatively modest, the direction of change may be clinically significant since an increase in PSA predicts clinical progression in the majority of men with prostate cancer. In the second test, the growth of LNCaP prostate cancer cells was inhibited almost eight times more by serum from the experimental than from the control group. Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. It was concluded that intensive lifestyle changes may affect the progression of early, low grade prostate cancer (Ornish et al., 2005).

In the late 1980s, increasing the consumption of beans, lentils, peas, tomatoes, raisins, dates and other dried fruit was found to be associated with a significantly decreased risk of prostate cancer (Mills et al., 1989). A decade later, a study of over 47,000 men confirmed an inverse link between fructose and prostate cancer indicating that eating fruit offers some protection against prostate cancer (Giovannucci et al., 1998a). More recently, in a review of diet, lifestyle and prostate cancer it was observed that while meat and dairy are associated with an increased risk, the consumption of tomato products (which contain the antioxidant lycopene), vitamin E and selenium supplements have all been shown to decrease risk. Tomato ketchup is a source of lycopene and organic brands may contain up to three times as much lycopene as non-organic (Ishida and Chapman, 2004). A high level of physical activity was also identified as a factor decreasing the risk of prostate cancer (Wolk, 2005).

Studies have shown that the consumption of soya foods may be associated with a reduction in cancer risk in humans. In a meta-analysis of 15 epidemiologic studies on soya consumption and nine on isoflavones (the plant hormones in soya foods) in association with prostate cancer risk, results showed that soya foods are associated with a reduction in prostate cancer risk. This protection may be associated with the type and quantity of soya foods consumed (Yan and Spitznagel, 2009).

In summary, the data linking the consumption of cow’s milk and dairy products to numerous different types of cancer provides a convincing argument for eliminating all animal foods from the diet while increasing the intake of whole grains, pulses (including soya), fruit and vegetables.