Prostate cancer risk factors
No established modifiable risk factor for prostate cancer has been identified and therefore, at present, there is insufficient evidence on which to base a prevention strategy. The established risk factors are age, family history and ethnicity.
Many other factors have been studied but the evidence for most of them remains inconclusive or conflicting. One reason for this may be that different factors are involved in the development and promotion of aggressive disease compared with non-aggressive disease, making epidemiological studies of prostate cancer particularly complex.1
Interpretation of prostate cancer risk factors has been further complicated in the PSA testing era, when identification of many prostate cancers is dependent on a threshold PSA level, which in turn is affected by other exposures such as body mass. This blurs the distinction between ‘cases’ and ‘controls’ leading to the possibility of PSA-detection bias.2
Meta-analyses and systematic reviews are cited on this page where available, as they provide the best overview of all available research and most take study quality into account. Individual case-control and cohort studies are reported where such aggregated data are lacking.
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A history of prostate cancer in a first-degree relative increases risk of the disease by 120–150%.3-5 The risk for men with an affected father is increased by 112–140%, while those with an affected brother have a 187–230% risk increase.3-5 The risk increase is higher when more than one first-degree relative is affected; for men aged under 65 years (compared with older men); and for men with a relative diagnosed before the age of 60.4-6 Risk is also increased, by 90–150%, for men with an affected second-degree relative.3,5
Men with a mother diagnosed with breast cancer have a 19–24% increased risk of prostate cancer, according to studies conducted in the United States and Sweden.6,7 Risk does not appear to be increased for men with a sister diagnosed with breast cancer.6,7
Germline mutations in the breast cancer susceptibility gene, BRCA2, can predispose men to prostate cancer, increasing the risk of developing prostate cancer up to five times in men overall, and more than seven times in men aged under 65.8 Mutations in the BRCA1 gene may increase the risk of developing prostate cancer in men under the age of 65 by a small amount, and there doesn’t appear to be an increased risk after this age.9,10
Recently, genome-wide association studies have identified several genetic variants that each slightly increase prostate cancer risk.11-18 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.
Overall, around 5–9% of prostate cancers are linked to genes and family history, it is estimated.19
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Black men have a higher risk of prostate cancer than white men, while men of Asian and Chinese ethnicity have a lower risk than white men, the latest England-wide data show.20 There are similar differences by major ethnic group in the United States.21 Compared to men born in England and Wales, men born in West Africa or the Caribbean, but resident in England and Wales, have standardised mortality ratios (SMRs) for prostate cancer of 271 and 198, while men born in India, Pakistan, Bangladesh and China and Hong Kong have SMRs between 21 and 72 (a SMR of 100 indicates a mortality rate similar to the whole population of England and Wales).22
The risk increase associated with black ethnicity is higher at younger ages, a cohort study shows, and black men may be diagnosed on average three–five years younger than white men, although firm conclusions about differences in the average age at diagnosis between ethnic groups are hampered by differences in the underlying population age distribution within these groups.23-25
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Men with the highest levels of insulin-like growth factor-1 (IGF-1) have a 38–83% increased risk of prostate cancer.26,27 The risk increase is stronger in studies where blood tests were taken after diagnosis of cancer (retrospective studies) but is also shown in prospective studies.28,29 Both a positive and negative association of prostate cancer risk with blood levels of IGF binding protein-3 (IGFBP-3) has been shown.27,28 Levels of IGF-2 and IGFBP-1 and IGFBP-2 do not appear to be associated with prostate cancer risk.27,28
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Men with a previous renal cell (kidney) cancer have an increased risk of prostate cancer, with a recent study showing a 69% increased risk.31,32 Risk associated with previous kidney cancer appears to be higher for men with a family history of prostate cancer.33 A 14–151% increased risk has been shown in various studies for men with a previous bladder cancer.33-36 This is at least partly due to detection bias, it has been suggested, although genetic factors may also play a role.34,35 Men with a previous melanoma have a 15–50% increased risk of prostate cancer, studies show.33,37-39 Men with a previous lung adenocarcinoma have a 56% increased risk of prostate cancer, according to an international registry study.40 A previous thyroid cancer has also been associated with an increased risk.41
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The International Agency for Research on Cancer (IARC) states that there is limited evidence that exposure to thorium-232 and its decay products, and gamma and x-rays increases prostate cancer risk.42 The risk increase for prostate cancer in atomic bomb survivors is consistent with that for all solid cancers.43
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Carotenoids and selenium
Foods containing lycopene (a carotenoid, or type of plant vitamin A) and selenium (a trace mineral) probably protect against prostate cancer, according the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR).44 Men with higher body levels (in blood or nail samples) of selenium have a 26–71% reduced risk of prostate cancer, according to meta-analyses.45,46 Men with the highest blood levels of lycopene have a 16–24% reduction in risk of prostate cancer, according to meta-analyses, although the lower, more recent, estimate was not statistically significant.47,48 Men with the highest intakes of lycopene have an 11% reduction in risk of prostate cancer, according to the earlier meta-analysis.48 Randomised controlled trials (RCTs) carried out to date do not show a reduced risk of prostate cancer in men receiving lycopene or selenium supplements.46,49,50
There is no association with blood levels of the other main individual carotenoids.47 Higher blood levels of total carotenoids were linked to a 65% reduced risk of advanced prostate cancer in a European cohort study, although it is possible that the association is due to another unidentified lifestyle factor associated both with a reduced likelihood of detection of prostate cancer at an early stage and lower intake of carotenoids.47
Current regular, long-term use of acetaminophen (>30 pills per month for at least five years) was linked to a 38% reduced risk of prostate cancer overall, and a 51% reduced risk of aggressive prostate cancer in a long-term study.53
Men with exposure to warfarin (a vitamin K antagonist, or anticoagulant) have a 17–31% reduced risk of prostate cancer, cohort and case-control studies show.54-56
Men with diabetes have a lower risk of prostate cancer, with the most recent meta-analysis showing a 21% reduction in risk for diabetic men in studies conducted in the United States only, and a similar risk reduction for men who had been diagnosed with diabetes between five and ten years earlier, but not for more a more recent diabetes diagnosis.57
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Testosterone is involved in growth of prostate cancer, but men with higher levels of testosterone in their blood prior to diagnosis do not appear to have a higher risk of prostate cancer.58 Risk of prostate cancer is also unrelated to levels of other androgens and oestrogen.58
A five-point increase in body mass index (BMI) is associated with a 9–15% increased risk of advanced prostate cancer or prostate cancer death, but with a 4–6% reduced risk of localised prostate cancer.59-61 Reduced likelihood of detecting prostate cancer at an early stage in obese men compared with those with a healthy bodyweight may partially explain the association of obesity with advanced prostate cancer, it has been suggested.61
Baldness at the age of 40 was associated with an 81% increased risk of prostate cancer before the age of 55, but a 44% reduction in risk for men aged 75 or older, in a recent cohort study.62 However, findings from earlier studies of baldness and prostate cancer have been inconsistent.
Heavy/long-term smoking is associated with an 11–22% increase in risk of prostate cancer, and current smokers have a 14% increased risk of dying of prostate cancer, with a risk increase of 24–30% for those with the highest exposures, according to a meta-analysis.63 There are difficulties in assessing the effect of smoking on prostate cancer risk, however, due to the potential for bias if factors related to prostate cancer risk vary between smokers and non-smokers, for example with regard to screening behaviour. IARC does not currently classify smoking as a cause of prostate cancer.42
Use of smokeless tobacco was linked to a 20% increased risk of prostate cancer in a meta-analysis, but the number of studies was small, and IARC does not classify smokeless tobacco as a cause of prostate cancer.42,64
There is no association between blood vitamin D levels and prostate cancer risk, according to a meta-analysis.65
There is no association between alcohol consumption and prostate cancer risk, meta-analyses show.66-68
Risk of prostate cancer is unrelated to intake of red and processed meat, when factoring in the effect of study quality and publication bias, according to the latest meta-analysis.69
Blood levels of vitamin E and retinol (vitamin A from animal sources) are not associated with prostate cancer risk, a meta-analysis shows.47
Folic acid supplements do not increase prostate cancer risk, according to the latest meta-analysis, and there is no association with blood levels of folate.70,71 These findings conflict with those of an earlier meta-analysis, which showed that men receiving folic acid supplements had a 24% increased risk of prostate cancer.72
Higher intake of dairy products may not be associated with risk of prostate cancer, according to the most recent meta-analysis.73 This contrasts with the results of an earlier meta-analysis, which showed a 12% increase in risk with higher intake of dairy products.74 Higher intake of butter and cheese, although not overall dairy products, may be associated with a 35–45% increased risk of advanced prostate cancer, according to a recent cohort study.75
Results of cohort studies into calcium intake and prostate cancer risk showed high variability and were not combined in the most recent meta-analysis, although an earlier analysis showed a 38% increase in risk with higher intake of calcium.73,74 Risk for total and advanced prostate cancer was increased by 32% and 62%, respectively, in a recent cohort study, and in 2007, the WCRF/AICR stated that there is probable evidence that diets high in calcium increase prostate cancer risk.44,75
Higher intake of alpha-linolenic acid (an omega-3 fatty acid found in plants) has been associated with both a reduction and increase in prostate cancer risk in meta-analyses.76,77 Research in this area is affected by publication bias meaning any effect shown may be spurious.78
High consumption of fish was not shown to affect prostate cancer risk in a meta-analysis of cohort studies, although was linked to a reduced risk of prostate cancer death.85
Green tea has been linked to a 57% reduction in prostate cancer risk in case-control studies, a meta-analysis shows, but as no effect was shown in cohort studies the evidence for an association remains uncertain.86
There is limited evidence that exposure to cadmium and cadmium compounds increases prostate cancer risk, IARC states.42 Cadmium is widely dispersed within the environment and the main source of exposure in non-smokers is through food. Men with the highest dietary exposure have a 29% increased risk of localised prostate cancer, a cohort study shows.89
Men with higher levels of occupational physical activity have a 19% reduced risk of prostate cancer, according to a meta-analysis, but recreational physical activity was shown to have no effect.90
Use of aspirin was linked to a 17% reduced risk of prostate cancer in the most recent meta-analysis, although there was considerable heterogeneity between the individual studies included in the analysis.91 A subsequent study showed a 12% reduced risk of aggressive prostate cancer in men taking at least one aspirin pill a day in the previous 12 months.92 Aspirin use does not reduce risk of prostate cancer death, according to a meta-analysis of RCTs.93 Because of the potential adverse consequences of high intake of aspirin, such as gastrointestinal haemorrhage, it would not be recommended as a prophylactic measure.
No significant effect of non-aspirin NSAIDs was shown in two meta-analyses.91,94 A risk increase for men taking several types of non-aspirin NSAID was shown in a recent study but this was thought to be a result of bias as there was no trend with increasing cumulative usage.95 Use of NSAIDs lowers PSA levels, which is a potential source of bias in studies of prostate cancer risk.96
The majority of meta-analyses of observational studies and RCTs show no effect of statin use on risk of prostate cancer.97-100 There has been one exception to this, where overall use was shown to slightly reduce prostate cancer risk, but long-term use was not.101
Prostatitis (inflammation of the prostate) can be caused by an infection, but in the majority of cases is of unknown cause. A history of prostatitis has been linked to a 60% increased risk of prostate cancer in a meta-analysis.102 Subsequent findings have been conflicting, one large prospective study showing a risk increase for men of all ages, and another showing a risk increase for men aged under 60 but a risk reduction for men aged over 69.103,104 Men with a diagnosis of any benign prostate disease (benign prostatic hyperplasia or prostatitis) in the previous five years have a 57% increased risk of prostate cancer, but the risk increase is limited to the first six months after the diagnosis, and not over a longer period of follow-up, according to a case-control study. This indicates that prostate cancer might be more likely to be incidentally detected during investigation for these conditions, rather than the conditions having a causal role in prostate cancer development.105
Evidence is conflicting about whether previous vasectomy is linked to an increased risk of prostate cancer, but the most comprehensive meta-analysis showed no risk increase.106-108
Men with a previous knee or hip replacement have a 12–19% increased risk of prostate cancer, meta-analyses show.109,110 However, the risk increase begins to occur within five years of the procedure, suggesting that the increased risk is a result of increased likelihood of detection of prostate cancer in this group.110
A history of sexually transmitted infections (STIs) has been linked to prostate cancer in meta-analyses (40–50% risk increase).111,112 However, the majority of studies included in these analyses were retrospective, meaning it is possible the results were affected by recall bias, and recent large prospective studies have shown no association of individual STIs or overall history of STIs with prostate cancer risk.103,104,113 Men with HIV or AIDS are not at an increased risk of prostate cancer, according to meta-analyses.114,115
Meta-analyses have shown a 13–24% increase in prostate cancer risk in men exposed to pesticides in their occupation.116-118 However, problems with comparing incidence of cancer in people in employment with the general population mean that the results may not be reliable. Prostate cancer was excluded from a recent analysis of occupation-related cancer in Britain, implying that there is inadequate evidence to link prostate cancer to occupational exposures.119 IARC states there is limited evidence of an increased risk of prostate cancer in relation to exposure to arsenic and inorganic arsenic compounds and the rubber production industry.42
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