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Genetics of Prostate Cancer (PDQ®)

Prostate Cancer Risk Assessment

The purpose of this section is to describe current approaches to assessing and counseling patients about susceptibility to prostate cancer. Genetic counseling for men at increased risk of prostate cancer encompasses all of the elements of genetic counseling for other hereditary cancers. (Refer to the PDQ summary on Cancer Genetics Risk Assessment and Counseling for more information.) The components of genetic counseling include concepts of prostate cancer risk, reinforcing the importance of detailed family history, pedigree analysis to derive age-related risk, and offering participation in research studies to those individuals who have multiple affected family members.[1,2] Genetic testing for prostate cancer susceptibility is not available outside of the context of a research study. Families with prostate cancer can be referred to ongoing research studies; however, these studies will not provide individual genetic results to participants.

Prostate cancer will affect an estimated one in seven American men during their lifetime.[3] Currently, evidence exists to support the hypothesis that approximately 5% to 10% of all prostate cancer is due to rare autosomal dominant prostate cancer susceptibility genes.[4,5] The proportion of prostate cancer associated with an inherited susceptibility may be even larger.[6-8] Men are generally considered to be candidates for genetic counseling regarding prostate cancer risk if they have a family history of prostate cancer. The Hopkins Criteria provide a working definition of hereditary prostate cancer families.[9] The three criteria include the following:

  1. Three or more first-degree relatives (father, brother, son), or
  2. Three successive generations of either the maternal or paternal lineages, or
  3. At least two relatives affected at or before age 55 years.

Families need to fulfill only one of these criteria to be considered to have hereditary prostate cancer. One study investigated attitudes regarding prostate cancer susceptibility among sons of men with prostate cancer.[10] They found that 90% of sons were interested in knowing whether there is an inherited susceptibility to prostate cancer and would be likely to undergo screening and consider genetic testing if there was a family history of prostate cancer; however, similar high levels of interest in genetic testing for other hereditary cancer syndromes have not generally been borne out in testing uptake once the clinical genetic test becomes available.

Risk Assessment and Analysis

Assessment of a man concerned about his inherited risk of prostate cancer should include taking a detailed family history; eliciting information regarding personal prostate cancer risk factors such as age, race, and dietary intake of fats and dairy products; documenting other medical problems; and evaluating genetics-related psychosocial issues.

Family history documentation is based on construction of a pedigree, and generally includes the following:

  • The history of cancer in both maternal and paternal bloodlines.
  • All primary cancer diagnoses (not just prostate cancer) and ages at diagnosis.
  • Race and ethnicity.
  • Other health problems including benign prostatic hypertrophy.[11]

(Refer to the Documenting the family history section in the PDQ summary on Cancer Genetics Risk Assessment and Counseling for a more detailed description of taking a family history.)

Analysis of the family history generally consists of four components:

  1. Evaluation of the pattern of cancers in the family to identify cancer clusters, which might suggest a known inherited cancer syndrome. In addition to site-specific prostate cancer, other cancer susceptibility syndromes include prostate cancer as a component tumor (e.g., hereditary breast/ovarian cancer syndrome [associated with mutations in BRCA1 and BRCA2]).
  2. Assessment for genetic transmission. The pedigree should be assessed for evidence of both autosomal dominant and X-linked inheritance, which may be associated with a higher likelihood of an inherited susceptibility to prostate cancer. Autosomal dominant transmission is characterized by the presence of affected family members in sequential generations, with approximately 50% of males in each generation affected with prostate cancer. X-linked inheritance is suggested by apparent transmission of susceptibility from affected males in the maternal lineage. (Refer to the Analysis of the Family History section in the PDQ summary on Cancer Genetics Risk Assessment and Counseling for more information.)
  3. Age at diagnosis of prostate cancer in the family. An inherited susceptibility to prostate cancer may be likely in families with early-onset (inconsistently defined) prostate cancer.[12] However, genetic research is also underway in families with an older age of prostate cancer onset. In the aggregate, the data are inconsistent relative to whether hereditary prostate cancer is routinely characterized by a younger-than-usual age at diagnosis.
  4. Risk assessment based on family and epidemiological studies. Multiple studies have reported that first-degree relatives of men affected with prostate cancer are two to three times more likely to develop prostate cancer than are men in the general population. In some studies, the relative risk (RR) of prostate cancer is highest among families who develop prostate cancer at an earlier age, consistent with other cancer susceptibility syndromes in which early age at onset is a common feature. It has been estimated that male relatives of men diagnosed with prostate cancer younger than 53 years have a 40% lifetime cumulative risk of developing prostate cancer.[13] A population-based case-control study of more than 1,500 cases and 1,600 controls, in which whites, African Americans, and Asian Americans were studied, reported an odds ratio of 2.5 for men with an affected first-degree relative after adjusting for age and ethnicity.[14] For men with a brother and father or son affected with prostate cancer, the RR was estimated to be 6.4.

A number of studies have examined the accuracy of the family history of prostate cancer provided by men with prostate cancer. This has clinical importance when risk assessments are based on unverified family history information. In an Australian study of 154 unaffected men with a family history of prostate cancer, self-reported family history was verified from cancer registry data in 89.6% of cases.[15] Accuracy of age at diagnosis within a 3-year range was correct in 83% of the cases, and accuracy of age at diagnosis within a 5-year range was correct in 93% of the cases. Self-reported family history from men younger than 55 years and reports about first-degree relatives had the highest degree of accuracy.[15] Self-reported family history of prostate cancer, however, may not be reliably reported over time,[16] which underscores the need to verify objectively reported prostate cancer diagnoses when trying to determine whether a patient has a significant family history.

The personal health and risk-factor history includes, but is not limited to, the following:

  • Family history.
  • Age.
  • Race.
  • Current and past diet history, including fat intake.
  • Current and past use of drugs that can affect prostatic growth, such as steroids (e.g., finasteride [Proscar]). (Refer to the PDQ summary on Prostate Cancer Prevention for more information about finasteride and prostate cancer.)
  • Current and past use of complementary and alternative medications (e.g., saw palmetto, PC-SPES).[17] (Refer to the PDQ summary on PC-SPES for more information.)

The most definitive risk factors for prostate cancer are age, race, and family history.[18] The correlation between other risk factors and prostate cancer risk is not clearly established. Despite this limitation, cancer risk counseling is an educational process that provides details regarding the state of the knowledge of prostate cancer risk factors. The discussion regarding these other risk factors should be individualized to incorporate the consultand's personal health and risk factor history. (Refer to the Risk Factors for Prostate Cancer section of this summary for a more detailed description of prostate cancer risk factors.)

The psychosocial assessment in this context might include evaluation of the following:

  • Level of psychological distress.
  • Perceived risk of prostate cancer.
  • Past history of depression, anxiety, or other mental illness.

One study found that psychological distress was greater among men attending prostate cancer screening who had a family history of the disease, particularly if they also reported an overestimation of prostate cancer risk. Psychological distress and elevated risk perception may influence adherence to cancer screening and risk management strategies. Consultation with a mental health professional may be valuable if serious psychosocial issues are identified.[19]

Genetic Testing

At this time, with the exception of prostate cancer in a family with evidence of hereditary breast/ovarian cancer (HBOC) syndrome, clinical genetic testing to detect inherited prostate cancer predisposition is not available. (Refer to the BRCA1 and BRCA2 section of this summary and the PDQ summary on Genetics of Breast and Gynecologic Cancers for more information about prostate cancer in HBOC.) None of the candidate susceptibility genes have been unequivocally associated with prostate cancer predisposition. For families suspected of having an inherited susceptibility to prostate cancer, participation in ongoing research studies investigating the genetic basis of inherited prostate cancer susceptibility can be considered.

References

  1. Nieder AM, Taneja SS, Zeegers MP, et al.: Genetic counseling for prostate cancer risk. Clin Genet 63 (3): 169-76, 2003. [PUBMED Abstract]
  2. Bruner DW, Baffoe-Bonnie A, Miller S, et al.: Prostate cancer risk assessment program. A model for the early detection of prostate cancer. Oncology (Huntingt) 13 (3): 325-34; discussion 337-9, 343-4 pas, 1999. [PUBMED Abstract]
  3. American Cancer Society: Cancer Facts and Figures 2014. Atlanta, Ga: American Cancer Society, 2014. Available online. Last accessed November 24, 2014.
  4. Steinberg GD, Carter BS, Beaty TH, et al.: Family history and the risk of prostate cancer. Prostate 17 (4): 337-47, 1990. [PUBMED Abstract]
  5. Carter BS, Beaty TH, Steinberg GD, et al.: Mendelian inheritance of familial prostate cancer. Proc Natl Acad Sci U S A 89 (8): 3367-71, 1992. [PUBMED Abstract]
  6. Lesko SM, Rosenberg L, Shapiro S: Family history and prostate cancer risk. Am J Epidemiol 144 (11): 1041-7, 1996. [PUBMED Abstract]
  7. Grönberg H, Damber L, Damber JE, et al.: Segregation analysis of prostate cancer in Sweden: support for dominant inheritance. Am J Epidemiol 146 (7): 552-7, 1997. [PUBMED Abstract]
  8. Schaid DJ, McDonnell SK, Blute ML, et al.: Evidence for autosomal dominant inheritance of prostate cancer. Am J Hum Genet 62 (6): 1425-38, 1998. [PUBMED Abstract]
  9. Carter BS, Bova GS, Beaty TH, et al.: Hereditary prostate cancer: epidemiologic and clinical features. J Urol 150 (3): 797-802, 1993. [PUBMED Abstract]
  10. Bratt O, Kristoffersson U, Lundgren R, et al.: Sons of men with prostate cancer: their attitudes regarding possible inheritance of prostate cancer, screening, and genetic testing. Urology 50 (3): 360-5, 1997. [PUBMED Abstract]
  11. Pienta KJ, Esper PS: Risk factors for prostate cancer. Ann Intern Med 118 (10): 793-803, 1993. [PUBMED Abstract]
  12. Giovannucci E: How is individual risk for prostate cancer assessed? Hematol Oncol Clin North Am 10 (3): 537-48, 1996. [PUBMED Abstract]
  13. Neuhausen SL, Skolnick MH, Cannon-Albright L: Familial prostate cancer studies in Utah. Br J Urol 79 (Suppl 1): 15-20, 1997. [PUBMED Abstract]
  14. Whittemore AS, Wu AH, Kolonel LN, et al.: Family history and prostate cancer risk in black, white, and Asian men in the United States and Canada. Am J Epidemiol 141 (8): 732-40, 1995. [PUBMED Abstract]
  15. Gaff CL, Aragona C, MacInnis RJ, et al.: Accuracy and completeness in reporting family history of prostate cancer by unaffected men. Urology 63 (6): 1111-6, 2004. [PUBMED Abstract]
  16. Weinrich SP, Faison-Smith L, Hudson-Priest J, et al.: Stability of self-reported family history of prostate cancer among African American men. J Nurs Meas 10 (1): 39-46, 2002 Spring-Summer. [PUBMED Abstract]
  17. Barqawi A, Gamito E, O'Donnell C, et al.: Herbal and vitamin supplement use in a prostate cancer screening population. Urology 63 (2): 288-92, 2004. [PUBMED Abstract]
  18. Stanford JL, Stephenson RA, Coyle LM, et al., eds.: Prostate Cancer Trends 1973-1995. Bethesda, Md: National Cancer Institute, 1999. NIH Pub. No. 99-4543. Also available online. Last accessed June 18, 2014.
  19. Taylor KL, DiPlacido J, Redd WH, et al.: Demographics, family histories, and psychological characteristics of prostate carcinoma screening participants. Cancer 85 (6): 1305-12, 1999. [PUBMED Abstract]
  • Updated: December 5, 2014