Cancer Research UK : Prostate Cancer risk factors

Prostate Cancer risk factors

No easily modifiable risk factor for prostate cancer has been identified and therefore, at present, there is insufficient evidence on which to base a prevention strategy.

This section contains information on the risk factors of prostate cancer and includes age and ethnicity, family history, diet, alcohol, Insulin-like growth factor and other risk factors.

Prostate cancer risk factors - Age and ethnicity

The strongest known risk factor is age, with very low risk in men under 50 and rising risk with increasing age thereafter (Figure 4.1).

Variation in incidence rates around the world, together with racial differences within countries, suggests that risk is affected by ethnicity. The highest rates in the world are recorded in African-American men, who have much higher rates than white Americans. The lowest rates are recorded in Asian men.1 In England, rates in men of South Asian origin are significantly lower than in other ethnic groups.2

Figure 4.1: Numbers of new cases and age-specific incidence rates, prostate cancer, UK 2002

Download this chart (23.5kb)

Prostate cancer risk factors - Family history

Risk increases two to three times for men with a family history of prostate cancer in a first-degree relative. The risk appears to be higher if the relative is a brother rather than a father, suggesting that the disease is recessive or linked to the X chromosome.3

Risk is also increased if the affected relative is young or if more than one relative is affected. It has been estimated that a predisposing gene could be responsible for 43% of cases by age 55, and up to 10% of all cases.4 Men whose families have an increased risk of breast cancer are also at higher risk of prostate cancer. For more details, see the Molecular Biology and Genetics section.

Prostate cancer risk factors - Diet

The high rates of prostate cancer found in developed countries have been associated with the western diet, particularly the high intake of animal fat. Japanese migrants to the USA increase their risk of developing prostate cancer. This has been linked to changes in the diet of these individuals, just as increasing rates in the traditionally low-risk countries, such as China and Japan, have been associated with the westernisation of diet. It is possible that a high-fat diet might affect the male sex hormone, testosterone , which controls the growth and function of the prostate, but the epidemiological evidence is at present inconclusive. Prostate cancer is known to be hormone-dependent (see Treatment section) and rarely develops in castrated men.

Recently, studies have attempted to clarify the association between prostate cancer and the two essential fatty acids, alpha-linolenic acid and linoleic acid. Results suggest that alpha-linolenic acid (found in animal fat, vegetable oils and nuts) is associated with an increased risk5-6, while linoleic acid, found in vegetable oils, protects against prostate cancer.6-7 Hypercholesterolaemia and hyperlipidaemia have been associated with an increased risk of prostate cancer.8-9

Cohort and case-control studies have reported significant increases in risk of prostate cancer or death from prostate cancer associated with consumption of pork10, or processed and red meats.11-12 An American cohort study reported a significantly increased risk in men consuming more than 10 g/day of very well cooked meat. This may be linked to heterocyclic amines or polycyclic aromatic hydrocarbons formed when meat is cooked at high temperatures or barbecued.13

Calcium intake may also have a role in the aetiology of this disease. A recent meta-analysis found a significant risk increase for advanced prostate cancer of about 30% for men with the highest consumption of dairy products, but no significant increase in risk for higher calcium intake.14 In general, these studies have not adjusted for fat intake and it is possible that results are confounded by this factor. A randomised trial found no significant increase in risk in men receiving calcium supplements, or in men with higher dietary calcium intake.15 A lowered risk is reported for users of calcium channel blockers.16 More studies are needed to clarify the role of calcium in prostate cancer.

Some dietary factors may have a protective effect against prostate cancer, including selenium, vitamin E and lycopene, but the evidence is not yet conclusive. The Nutritional Prevention of Cancer trial in the United States found a 65% reduction in prostate cancer incidence among those receiving selenium supplementation compared with those receiving a placebo.17-18 A meta-analysis of studies published since 1966 found a significant risk reduction of about 30% in men with the highest dietary intake of selenium.19

However, a recent British study found no strong association between prostate cancer risk and selenium concentration in the body, as measured in nail clippings.20 A large US study has recently reported a significant 80% reduction in risk of advanced prostate cancer in male smokers taking the highest dose of vitamin E supplements.21 Previously, two prospective cohort studies and one randomised trial showed risk reductions in current smokers reporting regular use of alpha-tocopherol supplements; in one of the cohort studies the risk reduction was limited to advanced cases.22-24

Several earlier studies also show a significant risk reduction with higher serum levels of alpha-tocopherol25 or gamma-tocopherol,26-27 while others do not.28-29 A large prospective randomised trial (Selenium and Vitamin E Cancer Prevention Trial) looking at the association between these two micronutrients and prostate cancer is underway in the USA. Recruitment to the trial has stopped, but results will not be reported for a number of years.30-31

A third collection of nutrients with antioxidant properties, the carotenoids, lycopene, alpha-carotene and beta-carotene, have been studied for a possible protective effect against prostate cancer. The evidence seems strongest for lycopene, found principally in tomatoes and tomato-based products. A meta-analysis of studies published from 1966–2003 found a significant risk reduction of 10–25% for men with the highest lycopene intake or blood levels, and for men consuming the highest quantity of cooked tomato products.32

While individual nutrients have been studied for their effects on prostate cancer risk, data from the European Prospective Investigation into Cancer and Nutrition (EPIC study) showed no association between total fruit and vegetable intake and risk among 130,000 men.33

Prostate cancer risk factors - Alcohol

A meta-analysis published in 2001 found a small but significant increased risk for men drinking more than 50 g/day of alcohol, with a slightly higher risk for men consuming more than 100 g/day.34 Since that analysis, cohort studies in America have found increased risks for men drinking moderate amounts of spirits, and for ‘binge drinkers,35 but moderate consumption of beer or wine has not been linked to an increased risk.36-37

Prostate cancer risk factors - Insulin-like growth factor (IGF-1)

Insulin-like growth factor is an easily measurable protein that is involved in normal cell proliferation and death. A recent meta-analysis found that higher concentrations of IGF-1 were associated with an increased risk of prostate cancer and there was a clear dose-response relationship.38 Since then, a large Swedish case-control study also reported a significantly increased risk of prostate cancer in men with the highest levels of IGF-1, with the strongest association in men under the age of 59,39 but case-control studies carried out in the US and France reported no association.40-41

IGF-1 levels are affected by other cancer risk factors such as bodyweight, diet and levels of physical activity and it is noteworthy that IGF-1 levels decrease with age in direct contrast to the risk of prostate cancer. The relationship between IGF-1 levels and prostate cancer requires further investigation.

Other prostate cancer risk factors

The risk of prostate cancer is significantly lower among men with diabetes mellitus than among those without the condition.42 The mechanism is not known. One suggestion is that it is related to IGF-1 levels, which are reduced in diabetics. Another possible mechanism involves testosterone: men with diabetes mellitus are more likely to have decreased testosterone levels.

A systematic review reported a significant 10% reduction in risk in men taking aspirin,43 and a large cohort study from the US published since this analysis reported significant risk reductions of 18% and 15% for men taking more than 30 aspirin, or any NSAIDs, respectively, per month for at least five years.44

Meta-analyses have reported a significant increase in risk of prostate cancer of 24% for men working as pesticide applicators,45 and 28% for those working in pesticide manufacture.46

Vasectomy may be linked with a moderate increased risk of prostate cancer, although mechanisms are unclear and more studies are needed to rule out confounding of study results by surveillance bias.47-48

References

Parkin, D.M., et al., ed.^eds. Cancer Incidence in Five Continents Volume VIII. ed. IARC Scientific Publications, ed. Vol. 155. 2002, IARC Scientific Publications: Lyon, France
Winter, H., et al., Cancer incidence in the south Asian population of England (1990-92). Br J Cancer, 1999. 79(3-4): p. 645-54.PubMed
Monroe, K., et al., Evidence of an X-linked or recessive genetic component to prostate cancer risk. Nat Med, 1995. (1): p. 827-829.PubMed
Elo, J.P. and T. Visakorpi, Molecular genetics of prostate cancer. Ann Med, 2001. 33(2): p. 130-41.PubMed
Brouwer, I.A., M.B. Katan, and P.L. Zock, Dietary alpha-linolenic acid is associated with reduced risk of fatal coronary heart disease, but increased prostate cancer risk: a meta-analysis. J Nutr, 2004. 134(4): p. 919-22.PubMed
Leitzmann, M.F., et al., Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. Am J Clin Nutr, 2004. 80(1): p. 204-16.PubMed
Laaksonen, D.E., et al., Serum linoleic and total polyunsaturated fatty acids in relation to prostate and other cancers: a population-based cohort study. Int J Cancer, 2004. 111(3): p. 444-50.PubMed
Bravi, F., et al., Self-reported history of hypercholesterolaemia and gallstones and the risk of prostate cancer. Ann Oncol, 2006. p.PubMed
Kaye, J.A. and H. Jick, Statin use and cancer risk in the General Practice Research Database. Br J Cancer, 2004. 90(3): p. 635-7.PubMed
Rodriguez, C., et al., Jewish ethnicity and prostate cancer mortality in two large US cohorts. Cancer Causes Control, 2002. 13(3): p. 271-7.PubMed
Walker, M., et al., Dietary patterns and risk of prostate cancer in Ontario, Canada. Int J Cancer, 2005. 116(4): p. 592-8.PubMed
Jian, L., et al., Do preserved foods increase prostate cancer risk? Br J Cancer, 2004. 90(9): p. 1792-5.PubMed
Cross, A.J., et al., A prospective study of meat and meat mutagens and prostate cancer risk. Cancer Res, 2005. 65(24): p. 11779-84.PubMed
Gao, X., M.P. LaValley, and K.L. Tucker, Prospective studies of dairy product and calcium intakes and prostate cancer risk: a meta-analysis. J Natl Cancer Inst, 2005. 97(23): p. 1768-77.PubMed
Baron, J.A., et al., Risk of prostate cancer in a randomized clinical trial of calcium supplementation. Cancer Epidemiol Biomarkers Prev, 2005. 14(3): p. 586-9.PubMed
Debes, J.D., et al., Inverse association between prostate cancer and the use of calcium channel blockers. Cancer Epidemiol Biomarkers Prev, 2004. 13(2): p. 255-9.PubMed
Li, H., et al., A prospective study of plasma selenium levels and prostate cancer risk. J Natl Cancer Inst, 2004. 96(9): p. 696-703.PubMed
Duffield-Lillico, A.J., et al., Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Prevention of Cancer Trial. Cancer Epidemiol Biomarkers Prev, 2002. 11(7): p. 630-9.PubMed
Etminan, M., et al., Intake of selenium in the prevention of prostate cancer: a systematic review and meta-analysis. Cancer Causes Control, 2005. 16(9): p. 1125-31.PubMed
Allen, N.E., et al., A case--control study of selenium in nails and prostate cancer risk in British men. Br J Cancer, 2004. 90(7): p. 1392-6.PubMed
Kirsh, V.A., et al., Supplemental and dietary vitamin E, beta-carotene, and vitamin C intakes and prostate cancer risk. J Natl Cancer Inst, 2006. 98(4): p. 245-54.PubMed
Rodriguez, C., et al., Vitamin E supplements and risk of prostate cancer in U.S. men. Cancer Epidemiol Biomarkers Prev, 2004. 13(3): p. 378-82.PubMed
ATBC Study Group, Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up. JAMA, 2003. 290(4): p. 476-85.PubMed
Chan, J.M., et al., Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States. Cancer Epidemiol Biomarkers Prev, 1999. 8(10): p. 893-9.PubMed
Goodman, G.E., et al., The association between lung and prostate cancer risk, and serum micronutrients: results and lessons learned from beta-carotene and retinol efficacy trial. Cancer Epidemiol Biomarkers Prev, 2003. 12(6): p. 518-26.PubMed
Huang, H.Y., et al., Prospective study of antioxidant micronutrients in the blood and the risk of developing prostate cancer. Am J Epidemiol, 2003. 157(4): p. 335-44.PubMed
Helzlsouer, K.J., et al., Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. J Natl Cancer Inst, 2000. 92(24): p. 2018-23.PubMed
Schuurman, A.G., et al., A prospective cohort study on intake of retinol, vitamins C and E, and carotenoids and prostate cancer risk (Netherlands). Cancer Causes Control, 2002. 13(6): p. 573-82.PubMed
Meyer, F., et al., Antioxidant vitamin and mineral supplementation and prostate cancer prevention in the SU.VI.MAX trial. Int J Cancer, 2005. 116(2): p. 182-6.PubMed
Selenium and Vitamin E Cancer and Prevention Trial (SELECT). Accessed href="http://www.clinicaltrials.gov/ct/show/NCT00006392" target="_blank" title="this link will open in a new window">Link
Lippman, S.M., et al., Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT). J Natl Cancer Inst, 2005. 97(2): p. 94-102.PubMed
Etminan, M., B. Takkouche, and F. Caamano-Isorna, The role of tomato products and lycopene in the prevention of prostate cancer: a meta-analysis of observational studies. Cancer Epidemiol Biomarkers Prev, 2004. 13(3): p. 340-5.PubMed
Key, T.J., et al., Fruits and vegetables and prostate cancer: No association among 1,104 cases in a prospective study of 130,544 men in the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer, 2004. 109(1): p. 119-24.PubMed
Bagnardi, V., et al., A meta-analysis of alcohol drinking and cancer risk. Br J Cancer, 2001. 85(11): p. 1700-5.PubMed
Platz, E.A., et al., Alcohol intake, drinking patterns, and risk of prostate cancer in a large prospective cohort study. Am J Epidemiol, 2004. 159(5): p. 444-53.PubMed
Sesso, H.D., R.S. Paffenbarger, Jr., and I.M. Lee, Alcohol consumption and risk of prostate cancer: The Harvard Alumni Health Study. Int J Epidemiol, 2001. 30(4): p. 749-55.PubMed
Schoonen, W.M., et al., Alcohol consumption and risk of prostate cancer in middle-aged men. Int J Cancer, 2005. 113(1): p. 133-40.PubMed
Renehan, A., Zwahlen, M, Minder, C, O'Dwyer, S T, Shalet, S M and Egger, M, Insulin-like growth factor (IGF)-1, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet, 2004. 363: p. 1346-53.PubMed
Stattin, P., et al., High levels of circulating insulin-like growth factor-I increase prostate cancer risk: a prospective study in a population-based nonscreened cohort. J Clin Oncol, 2004. 22(15): p. 3104-12.PubMed
Woodson, K., et al., Serum insulin-like growth factor I: tumor marker or etiologic factor? A prospective study of prostate cancer among Finnish men. Cancer Res, 2003. 63(14): p. 3991-4.PubMed
Meyer, F., et al., A prospective study of the insulin-like growth factor axis in relation with prostate cancer in the SU.VI.MAX trial. Cancer Epidemiol Biomarkers Prev, 2005. 14(9): p. 2269-72.PubMed
Bonovas, S., K. Filioussi, and A. Tsantes, Diabetes mellitus and risk of prostate cancer: a meta-analysis. Diabetologia, 2004. 47(6): p. 1071-8.PubMed
Mahmud, S., E. Franco, and A. Aprikian, Prostate cancer and use of nonsteroidal anti-inflammatory drugs: systematic review and meta-analysis. Br J Cancer, 2004. 90(1): p. 93-99.PubMed
Jacobs, E.J., et al., A large cohort study of aspirin and other nonsteroidal anti-inflammatory drugs and prostate cancer incidence. J Natl Cancer Inst, 2005. 97(13): p. 975-80.PubMed
Van Maele-Fabry, G. and J.L. Willems, Occupation related pesticide exposure and cancer of the prostate: a meta-analysis. Occup Environ Med, 2003. 60(9): p. 634-42.PubMed
Van Maele-Fabry, G., et al., Review and Meta-analysis of Risk Estimates for Prostate Cancer in Pesticide Manufacturing Workers. Cancer Causes Control, 2006. 17(4): p. 353-73.PubMed
Dennis, L.K., D.V. Dawson, and M.I. Resnick, Vasectomy and the risk of prostate cancer: a meta-analysis examining vasectomy status, age at vasectomy, and time since vasectomy. Prostate Cancer Prostatic Dis, 2002. 5(3): p. 193-203.PubMed
Rohrmann, S., et al., Association of vasectomy and prostate cancer among men in a Maryland cohort. Cancer Causes Control, 2005. 16(10): p. 1189-94.PubMed

Next section - Molecular biology and genetics