Prostate Cancer risk factors

The strongest known risk factor for prostate cancer is age, with very low risk in men under 50 and rising risk with increasing age thereafter ( Figure 4.1). The older the man, the higher the risk and this ties in with post-mortem results where approximately 80% of men by age 80 were shown to have cancer cells in their prostate. 3

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A family history of prostate cancer is one of the strongest known risk factors for this disease. It has been estimated that 5-10% of all prostate cancer cases and 30-40% of early-onset cases (men diagnosed <55 years) are caused by inherited susceptibility genes. 4, 5

Risk increases two to three times for men with a first-degree relative diagnosed with prostate cancer. 6 If the relative is <60 years old at diagnosis or more than one relative is affected (at any age), the individual’s risk is four times the average. These factors combine so that if more than one relative is affected by early-onset prostate cancer, the risk is increased by seven-fold. 5

A strong family history of breast cancer may also affect a man’s risk of prostate cancer, particularly if the family members were diagnosed under the age of 60. In particular, germline mutations in the breast cancer susceptibility genes, BRCA1 and BRCA2, can predispose men to prostate cancer (for more detail see  Molecular biology and genetics)

Recently, genome-wide association studies have identified several genetic variants that each slightly increase prostate cancer risk. 7-11 However, because such genetic variants are common in the population, they may contribute to a significant proportion of all prostate cancer cases. Current research in this area is likely to identify further variants in the next few years. Genetic profiling is being used to inform prostate screening and treatment.

Variation in incidence rates around the world and within countries, suggests that risk is affected by ethnicity. In the UK, black Caribbean and black African men have approximately two to three times the risk of being diagnosed or dying from prostate cancer than white men, while Asian men generally 12 have a lower risk than the national average. 12-14

These results echo those from the USA where black American men have higher rates than white American men and indeed the highest recorded in the world, while Asian American men have much lower rates. However, migration studies show an increase in risk as men move from low-risk to higher-risk countries, suggesting that lifestyle factors play an important role. For example, South Asian men living in the UK have a higher risk of prostate cancer than men living in South Asia. 15

Diet has been extensively researched because of the large variation in prostate cancer incidence between different cultures and their traditional diets around the world, particularly the Asian versus ‘western’ diet. A variety of factors have been looked at but much of the research is at present inconclusive. A recent review of the evidence concluded that foods containing lycopenes and selenium probably have a protective effect while diets high in calcium may increase risk. 16

Lycopene

Lycopene, found principally in tomatoes and tomato-based products, may reduce the risk of prostate cancer. Cooked and processed tomatoes, such as tomato sauce, are a better source of lycopene than fresh tomatoes. A meta-analysis of 21 studies published from 1966-2003, showed that men with the highest intake of cooked tomato products had a 20% reduced risk of prostate cancer compared to men with the lowest intake. 17

Since then, three studies including the European Investigation into Cancer and Nutrition (EPIC) study 18-20 have shown a significant protective effect with higher intake of lycopene, although three other studies showed no association. 21-23

Selenium

Several studies have shown a protective association for selenium, reporting a 30-80% risk reduction for prostate cancer. 24-26 However, at least three studies showed no association. 27-30 In addition,the Selenium and Vitamin E Cancer Prevention Trial (SELECT) has not shown a reduction in prostate cancer risk for men receiving selenium and vitamin E supplements. 30

Calcium and dairy products

Some cohort studies have shown a raised risk of prostate cancer for men with high intakes of calcium from diet and/or supplementation 31-34 but others have not. 35-37

Dairy products, as a source of calcium, have been extensively studied in relation to prostate cancer. Several cohort studies show a small significant increase in risk but findings differ by whether it affects advanced or localised tumours. 34-39

The EPIC study showed overall a 32% increased risk for 35g/day higher intake of dairy protein and a 7% risk increase for an 0.3g/day intake of dairy calcium. Protein and calcium from non-dairy sources were not associated with risk. 40

Fat and meat

Extensive research into fat intake has been inconclusive. One difficulty is measurement of the different types of fat intake including saturated and unsaturated fat as well as fatty acids such as ?-linolenic acid , an omega-3 polyunsaturated fatty acid. A recent large multi-ethnic cohort study found no increase in prostate cancer for any source of fat and therefore did not support earlier studies that showed a raised risk. 41

Further studies are needed, especially as ?-linolenic acid may protect against cardiovascular disease and therefore its role for prostate cancer needs to be clarified. 42 Meat intake, particularly red and processed meat , has been studied in relation to prostate cancer but findings are inconsistent.

Fruit and vegetables

Some studies 43-45 have shown a lower risk of prostate cancer for men consuming high quantities of cruciferous vegetables but this was not confirmed in the EPIC study which studied 130,000 men and found no association between total fruit and vegetable intake or cruciferous vegetables and risk of prostate cancer. 46

Vitamin E, green tea and soy

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in smokers showed a 32% reduction in risk of prostate cancer in men receiving daily alpha-tocopherol (the major form of vitamin E in supplements). 47 Other studies have shown little or no association. Further research is underway to clarify the equivocal results, in the SELECT trial. 30

Green tea has been studied due to its regular consumption by Japanese and Chinese men whose prostate cancer risk is low. Green tea contains high level of polyphenols which have anti-oxidant effects. 48 One cohort 49 and one case-control study 50 showed a reduced risk of prostate cancer with green tea consumption and a dose-response relationship with the quantity drunk, although a third study found no effect. 51 More research into the possible chemopreventive properties of green tea is needed.

East Asian diets have higher soy content than western diets, for example, with the consumption of tofu, soymilk and miso. As the incidence of prostate cancer is lower in these countries, soy and isoflavones have been studied to see if they are protective factors but findings are inconsistent.

Two meta-analyses of alcohol consumption and prostate cancer have been carried out. The largest study found no association 52 whilst the other showed only small risk increases, although dose-related, of 5%, 9% and 19% with consumption of 25, 50 and 100 grams per day . 53 Findings since these meta-analyses have been inconsistent.

A higher risk of fatal prostate cancer in smokers compared to non-smokers has been shown in some studies. 54, 55 However, no clear trends were shown with number of cigarettes smoked per day or between current, ex- and never-smokers. Two large studies concluded that smoking is not likely to be linked to either the incidence or mortality of prostate cancer. 56, 57

Obesity is a major health problem in the UK and has been linked to several major cancers. 58, 59 However, it is not yet proven to be an important risk factor for prostate cancer.

A recent meta-analysis reported a small borderline significant increase in prostate cancer risk with increasing body mass index (BMI). 60 Some cohort studies indicate that obese men are at greater risk of dying from prostate cancer 61-63 while others have reported a reduced risk of localised prostate cancer in men with a high BMI. 64, 65 Although the evidence is far from clear for prostate cancer, general health advice would be for men to maintain a healthy BMI.

Physical inactivity 66 has been linked to several serious diseases such as diabetes and heart disease as well as some cancers, particularly colon cancer, but there is no strong link with prostate cancer. 59