4
Does prostate cancer “run in families”? If you have relatives who have had prostate cancer, are your chances higher of getting the disease?
Increasing age is the strongest predictor of a diagnosis of prostate cancer, but the second most important predictor is family history. Around 10–20% of men with prostate cancer have a family history of the disease (meaning that 80–90% don’t) [52]. Given what we have summarised earlier about many men dying with rather than from prostate cancer, and never knowing that they had the disease, it is possible that part of this apparent excess rate in men with a family history may be due to their higher participation in testing. We know of no studies that have considered this possibility. Men who have a first degree relative (a father or brother) who has had prostate cancer are twice as likely to be diagnosed with prostate cancer as men with no affected relative [53]. The risk increases with the increasing number of affected relatives and with decreasing age at the diagnosis of those with the disease. Men with family history of prostate cancer typically have the disease diagnosed six to seven years earlier than men without a family history [52]. This can often be due to increased concern about the disease in such men and their willingness to be regularly tested [54]. 50
The most recent and largest meta-analysis on family history and prostate cancer (a meta-analysis is a study which combines all published high quality studies about a topic to assess what they all say when combined together) found the following increased risks [55]. In summary, cancer risk increases with:
Table 7: Family history and the probability of prostate cancer diagnosis
| Relatives with prostate cancer | Relative risk (95% confidence interval) |
|---|---|
| One First degree relative (FDR) | 2.57 (2.32–2.84) |
| Brother only | 3.37 (2.07–3.83) |
| Father only | 2.17 (1.90–2.49) |
| Two or more FDRs | 5.08 (3.31–7.79) |
| One FDR diagnosed younger than 65 years | 2.47 (1.71–3.55) |
| One FDR diagnosed older than 65 years | 1.72 (1.41–2.10) |
Note: A relative risk (RR) of 1 means that there would be no difference for the probability of a prostate cancer diagnosis between a man with a family history of the disease and a man with no such history. A RR of 2.57 thus means that a man with the family history has 2.57 times the likelihood of such a diagnosis compared to a man with no such history.
Unfortunately, a reliable genetic test that can discriminate between men at risk and not at risk is currently unavailable [56].
The 2010 Prostate Cancer Foundation advertising campaign gave this message to men: all men over 50 should consult their doctor 51about being tested, and that all men between 40 and 50 with a “family history” of the disease should also consult their doctor. As we saw earlier, the great majority of prostate cancer diagnoses and deaths occur in older men. It follows from this that the great majority of men with a relative with a family history will have had those relatives diagnosed and/or die with prostate cancer late in life.
As stated above, the risk of being diagnosed with prostate cancer is increased by a factor of about two to three if your father had prostate cancer. For a man in his early 40s, this increases his risk of being diagnosed with prostate cancer from about one in 52,000 to about one in 17,000 to 26,000; for a man in his early 50s, it would increase the risk from about one in 1600 to about one in 500 to 800 (see Table 5).
Some who advocate PSA screening in younger men argue that prostate cancer is more aggressive when it is diagnosed in younger men. Recent, detailed studies have had conflicting results, some suggesting that prostate cancer diagnosed in younger men is more aggressive than average, others suggesting it is less aggressive [57, 58]. The outcomes of prostate cancer treatment in younger men are probably as good or better than those in older men. However, there is no doubt that men diagnosed with prostate cancer at a younger age have more at stake: their average life expectancy without prostate cancer is longer; left untreated, the prostate cancer has more time to cause further problems; if treated, the prostate cancer has more time to recur.
With some cancers, we know that avoidance of particular exposures (ultra-violet radiation from sunlight and solaria, radiation, smoking, asbestos, soil radon, certain industrial chemicals) can do much to reduce the risk of getting cancer. So what is the situation with preventing prostate cancer? 52
Dietary factors are associated with both the promotion and protection of many diseases and health-related conditions: some types of diet promote some cancers and others appear to protect against some cancers [59]. Different diets are associated with both a higher and lower prevalence of various diseases and there is growing community understanding of this broad principle. Indeed, in a recent study, 73% of Australian men who had a family history of prostate cancer believed that diet was a factor associated with prostate cancer [60]. So are there in fact diets which appear to be associated with a lower population incidence of prostate cancer?
If you search Google for “diet and prostate cancer” you will get 2,240,000 hits. The great majority of these are entrepreneurial complementary (alternative) medicine sites promoting and selling a large range of dietary supplements, most of which will probably do little but generate expensive urine for you. There is unfortunately little accepted scientific evidence that dietary modification (reducing or increasing the intake of certain foods or elements) is a reliable way of reducing the risk of acquiring prostate cancer. Below we summarise some of the more important systematic reviews and large trials in the accumulated evidence about whether this disease can be prevented.
A recently published report from Victoria, a multicultural state where one can find a diversity of diets, followed 14,627 men aged 34 to 75 years for an average of 13.6 years, and identified 1018 cases of prostate cancer in the study group. The study “found no association between any dietary pattern and prostate cancer risk overall” nor did it find any association with cancer aggressiveness, Gleason score (see p67) or age at diagnosis [61]. 53
Daily consumption of green tea has long been thought to have a protective effect on cancer. A July 2009 Cochrane review of the role of green tea consumption in reducing the incidence of cancer (including prostate cancer) involved 51 studies with more than 1.6 million participants. The review concluded that
The evidence that the consumption of green tea might reduce the risk of cancer was conflicting. This means that drinking green tea remains unproven in cancer prevention, but appears to be safe at moderate, regular and habitual use. [62]
In the US in particular, it has become common for men to try to regularly eat tomatoes because of beliefs that their high content of lycopene – an anti-oxidant – may protect against prostate cancer. An analysis of 19 published studies on this subject concluded
our results show that tomato products may play a role in the prevention of prostate cancer. However, this effect is modest. Despite the preventive benefits of lycopene found in this study, the existing evidence is not overwhelming enough to recommend the use of lycopene supplements in the prevention of prostate cancer.
The only benefit – which was statistically small – was seen in those who ate high amounts of tomato [63].
A large double-blinded trial of either and both selenium and vitamin E undertaken among 35,533 men recruited in 427 North American sites where the median follow-up period was 5.46 years showed that selenium (a trace mineral) or vitamin E, alone or in combination did 54not prevent prostate cancer in this population of relatively healthy men compared with placebo [64].
Finasteride is a drug which inhibits the action of 5a-reductase, the enzyme that converts testosterone to the more potent androgen dihydrotestosterone. It is used to treat benign prostatic hyperplasia or BPH (see p22) and is also used by millions of men around the world to control baldness. The development of finasteride also allowed the possibility of studies being conducted to see if lowering androgen levels in the prostate would reduce the risk of prostate cancer. The Prostate Cancer Prevention Trial [65] set out to test this hypothesis. It involved allocating
18,882 men aged 55 years and over who had normal digital rectal examinations and a PSA level of 3.0 ng per millilitre or lower to treatment with finasteride (5 mg per day) or placebo for seven years. Prostate biopsy was recommended if during the trial, the annual PSA level, adjusted for the effect of finasteride, exceeded 4.0 ng per millilitre or if the digital rectal examination was abnormal.
The study directors calculated that
60 per cent of participants would have prostate cancer diagnosed during the study or would undergo biopsy at the end of the study and the main outcome of interest was the prevalence of prostate cancer during the seven years of the study.
The study demonstrated that by taking this drug every day for seven years, 18.4% of the men on finasteride developed prostate cancer compared with 24.4% of men on the placebo, a relative reduction of 24.8% in prevalence over the seven-year period. 55
However, adverse sexual side effects were more common in the finasteride-treated men: reduced ejaculatory volume 60.4% in finasteride group vs 47.3% in control group; erectile dysfunction (67.4% vs 61.5%); loss of libido (65.4% vs 59.6%); gynecomastia (developing “man boobs”, 4.5% vs 2.8%). In addition, aggressive tumours of Gleason grade 7, 8, 9, or 10 were more common in the finasteride group (37%) than in the placebo group (22.2%). The study authors concluded that the drug
prevents or delays the appearance of prostate cancer, but this possible benefit … must be weighed against sexual side effects and the increased risk of high-grade prostate cancer.
By saying it “prevents”, they of course do not mean that it prevents the disease in all men taking it, but that it reduces the incidence of the disease. And the absolute size of this reduction was only 6% – 24.4% of men not taking the drug for seven years were diagnosed with prostate cancer, while 18.4% of the men on finasteride developed prostate cancer. Moreover and very tellingly,
there was no significant difference in the number of deaths between the two groups: five men in each group died from prostate cancer.
Subsequently, further analyses of this trial have suggested that there may not have been an increased risk of more aggressive cancers in the finasteride group after all [66, 67]. It is possible that this apparent increase was caused by biases in reporting the results of biopsies among men in the finasteride group. Analyses adjusting for this bias found little or no increased risk of high grade cancer with finasteride; in fact finasteride may even reduce the risk of developing aggressive prostate cancer, just as it appears to reduce the risk of prostate cancer overall. 56
So to summarise, we have good evidence that finasteride produces a modest reduction in prostate cancer with long term use. But those taking it have elevated levels of sexual problems. That information should be entered into men’s calculations when deciding whether to take it.
Because the prostate is a sexual organ which supplies fluid to the ejaculate, it is understandable that researchers have considered the possibility that frequency of ejaculation (high, low, and at what stages in life) might have something to do with prostate cancer. Studies have produced mixed findings. A large cohort study of 29,342 US health professional men found that
Most categories of ejaculation frequency were unrelated to risk of prostate cancer. However, high ejaculation frequency was related to decreased risk of total prostate cancer.
Averaged across their lifetime, men who reported 21 or more ejaculations per month compared with men reporting four to seven ejaculations per month had a reduced relative risk of prostate cancer of 0.67 (95% CI, 0.51–0.89) – in other words, a 33% reduced risk. Other than for this high frequency category of ejaculation, the authors concluded, “Our results suggest that ejaculation frequency is not related to increased risk of prostate cancer” [68]. However, a more recent study showed that men who engaged in frequent masturbation, of about two to seven times a week, during their 20s and 30s, had a higher rate of prostate cancer, while men who engaged in masturbation once a week during their 50s had a lower rate [69].
These studies do not really provide men with much confidence to embark on a changed ejaculatory regimen, justifying it with hopes of preventing prostate cancer. 57
A 2001 review of the published literature on whether being physically active might protect against prostate cancer found that the “epidemiologic data supporting this hypothesis are weak and inconsistent” [70]. But of course physical activity is to be recommended for its many other important health promoting effects, including the prevention of other types of cancer.