Genetics of Prostate Cancer - National Cancer Institute


Purpose of This PDQ Summary


Introduction


Prostate Cancer Susceptibility Loci


Polymorphisms and Prostate Cancer Susceptibility


Interventions in Familial Prostate Cancer


Prostate Cancer Risk Assessment


Psychosocial Issues in Prostate Cancer


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Psychosocial Issues in Prostate Cancer

Introduction
Risk Perception
Anticipated Interest in Genetic Testing
Hereditary Prostate Cancer Families and Screening
Screening behaviors
Quality of Life in Relation to Screening for Prostate Cancer Among Individuals at Increased Hereditary Risk

Introduction

Research to date has included survey, focus group, and correlation studies on psychosocial issues related to prostate cancer risk. (Refer to the PDQ summary on Cancer Genetics Risk Assessment and Counseling for further information on psychological issues related to genetic counseling for cancer risk assessment.) Genetic testing for prostate cancer susceptibility genes, when testing becomes available, has the potential to identify those at highest risk, which facilitates risk-reducing interventions and early detection of prostate cancer. Having an understanding of the motivations of men who may consider genetic testing for inherited susceptibility to prostate cancer will help clinicians and researchers anticipate interest in testing. Further, these data will inform the nature and content of counseling strategies for men and their families, including consideration of the risks, benefits, decision-making issues, and informed consent for genetic testing.

Risk Perception

Knowledge about risk for prostate cancer is thought to be a factor influencing men’s decisions to pursue prostate cancer screening and, possibly, genetic testing.[1] A study of 79 African American men (38 of whom had been diagnosed with prostate cancer; and the remainder who were unaffected but at high risk for prostate cancer) completed a nine–item telephone questionnaire assessing knowledge about hereditary prostate cancer. On a scale of 0 to 9, with 9 representing a perfect score, scores ranged from 3.5 to 9 with a mean score of 6.34. The three questions relating to genetic testing were the questions most likely to be incorrect. In contrast, questions related to inheritance of prostate cancer risk were answered correctly by the majority of subjects.[2] Overall, knowledge of hereditary prostate cancer was low, especially concepts of genetic susceptibility, indicating a need for increased education. An emerging body of literature is now exploring risk perception for prostate cancer among men with and without a family history. Table 4 provides a summary of studies examining prostate cancer risk perception.

Table 4. Summary of Cross-Sectional Studies of Prostate Cancer Risk Perception

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Study Population	Sample Size	Proportion of Study Population That Accurately Reported Their Risk	Other Findings
Unaffected men with a family history of prostate cancer [3]	120 men aged 40 to 72 years	40%
First-degree male relatives (FDR of men with prostate cancer [4]	105 men aged 40 to 70 years	62%
Men with brothers affected with prostate cancer [5]	111 men aged 33 to 78 years	Not available	38% of men reported their risk of prostate cancer to be the same or less than the average man.
FDR of men with prostate cancer and a community sample [6]	56 men with a FDR with prostate cancer and 100 men without a FDR with prostate cancer all older than 40 years	57%	29% of men with a FDR thought that they were at the same risk as the average man, and 14% believed that they were at somewhat lower risk than average.

Study conclusions vary regarding whether first-degree relatives of prostate cancer patients accurately estimate their prostate cancer risk. Some studies found that men with a family history of prostate cancer considered their risk to be the same as or less than that of the average man.[5,6] Other factors, including being married, have been associated with higher prostate cancer risk perception.[7] A confounder in prostate cancer risk perception was confusion between benign prostatic hyperplasia and prostate cancer.[3]

Anticipated Interest in Genetic Testing

A number of studies summarized in Table 5 have examined participants' interest in genetic testing, if such a test were available for clinical use. Factors found to positively influence the interest in genetic testing include:

Advice of their primary care physician.[8]
Combination of emotional distress and concern about prostate cancer treatment effects.[9]
Having children.[10]

Findings from these studies were not consistent regarding the influence of race, education, marital status, employment status, family history, and age on interest in genetic testing. The men studied expressed concerns about confidentiality of test results among employers, insurers, and family, as well as stigmatization, potential loss of insurability, and the cost of the test.[8] These concerns are similar to those that have been reported in women contemplating genetic testing for breast cancer predisposition.[11-16] Concerns voiced about testing positive for a mutation in a prostate cancer susceptibility gene included decreased quality of life secondary to interference with sex life in the event of a cancer diagnosis, increased anxiety, and elevated stress.[8]

Table 5. Summary of Cross-Sectional Studies of Anticipated Interest in Prostate Cancer Susceptibility Genetic Testing

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Study Population	Sample Size	Percent Expressing Interest in Genetic Testing	Other Findings
Prostate screening clinic participants [17]	342 men aged 40 to 97 years	89%	28% did not demonstrate an understanding of the concept of inherited predisposition to cancer
General population; 9% with positive family history [8]	12 focus groups with a total of 90 men aged 18 to 70 years	All focus groups
African American men [18]	320 men aged 21 to 98 years	87%	Most participants could not distinguish between genetic susceptibility testing and a prostate-specific antigen blood test
Men with and without first-degree male relatives with prostate cancer [9]	126 men older than 40 years; mean age 52.6 years	24% definitely; 50% probably
Swedish men with a FDR with prostate cancer [3]	110 men aged 40 to 72 years	76% definitely; 18% probably	89% definitely or probably wanted their sons to undergo genetic testing
Sons of Swedish men with prostate cancer [10]	101 men aged 21 to 65 years	90%; 100% of sons with 2 to 3 family members affected with prostate cancer	60% expressed worry about having an increased risk for prostate cancer
Healthy outpatient males with no history of prostate cancer [19]	400 men aged 40 to 69 years	82%
Healthy African American males with no history of prostate cancer [20]	413 African American men aged 40 to 70 years	87%	Belief in the efficacy of and intention to undergo prostate cancer screening was associated with testing interest

Overall, these reports and a study that developed a conceptual model to look at factors associated with intention to undergo genetic testing [21] have shown a significant interest in genetic testing for prostate cancer susceptibility despite concerns about confidentiality and potential discrimination. These findings must be interpreted cautiously in predicting actual prostate cancer genetic test uptake once testing is available. In both Huntington disease and hereditary breast and ovarian cancers, hypothetical interest before testing was possible was much higher than actual uptake following availability of the test.[22,23]

Hereditary Prostate Cancer Families and Screening

The proportion of prostate cancers attributed to hereditary causes is estimated to be 5% to 10%,[24] and the risk for prostate cancer increases with the number of blood relatives with prostate cancer and young age at onset of prostate cancer within families.[25] There is considerable controversy in prostate cancer about the use of serum prostate-specific antigen (PSA) measurement and digital rectal exam (DRE) for prostate cancer early detection in the general population, with different organizations suggesting significantly different screening algorithms and age recommendations. (Refer to the PDQ summary on Prostate Cancer treatment for more information on prostate cancer in the general population, and the Interventions section of this summary for more information on inherited prostate cancer susceptibility.) This variation is likely to add to patient and provider confusion about recommendations for screening by members of hereditary cancer families or first-degree relatives of prostate cancer patients. Psychosocial questions of interest include what individuals at increased risk understand about hereditary risk, whether informational interventions are associated with increased uptake of prostate cancer screening behaviors, and what the associated quality-of-life implications of screening are for individuals at increased risk. Also of interest is the role of the primary care provider in helping those at increased risk identify their risk and undergo age- and family-history–appropriate screening. The literature on psychosocial aspects of hereditary prostate cancer is quite limited, but there are implications from even the small number of current studies for primary care practice.

Screening behaviors

In most cancers, the goal of improved knowledge of hereditary risk can be translated rather easily into a desired increase in adherence to approved and recommended (if not proven) screening behaviors. This is complicated for prostate cancer screening by the lack of clear recommendations for men in both high-risk and general populations. (Refer to the Screening section of this summary for more information.) In addition, controversy exists with regard to the value of early diagnosis of prostate cancer. This creates uncertainty for patients and providers and challenges the psychosocial factors related to screening behavior.

Several small studies have examined the behavioral correlates of prostate cancer screening at average and increased prostate cancer risk based on family history; these are summarized in Table 6. In general, results appear contradictory whether men with a family history are more likely to be screened than those not at risk, and whether the screening is appropriate for their risk status. Furthermore, most of the studies had relatively small numbers of subjects, and the criteria for screening were not uniform, making generalization difficult.

Table 6. Summary of Studies of Behavioral Correlates for Prostate Cancer Screening

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Study Population	Sample Size	Percent Undergoing Screening	Predictive Correlates for Screening Behavior
DRE = digital rectal exam; NHIS = National Health Interview Survey; PSA = prostate-specific antigen.
Unaffected men with at least one first-degree relative with prostate cancer.[26]	82 men (aged ≥40 years; mean age 50.5 years).	PSA	Aged >50 years.
		50% reported PSA screening within the previous 14 months.	Annual income ≥U.S. $40,000.
			History of PSA screening prior to study enrollment.
			Higher levels of self-efficacy and response efficacy for undergoing prostate cancer screening.
Sons of men with prostate cancer.[27]	124 men (60 men with a history of prostate cancer aged 38–84 years, median age 59 years; 64 unaffected men aged 31–78 years, median age 55 years).	PSA	39.4% patient request.
		Unaffected men: 95.3% reported ever having a PSA test.	35.6% physician request.
		Affected men: 71.7% reported ever having a PSA test prior to diagnosis.
		DRE
		Unaffected men: 96.9% reported ever having a DRE.
		Affected men: 91.5% reported ever having a DRE prior to diagnosis.
		Both PSA and DRE
		Unaffected men: 93.8% had both.
		Affected men: 70.0% reported having both prior to diagnosis.
Unaffected men with and without a first-degree relative with prostate cancer.[6]	156 men aged ≥40 years (56 men with a first-degree relative; 100 men without a first-degree relative).	PSA	Older age.
		63% reported ever having a PSA test.	First-degree relatives reported higher disease vulnerability and less belief in disease prevention, but this did not result in increased prostate cancer screening when compared to those without a first-degree relative.
		DRE
		86% reported ever having a DRE.
Unaffected Swedish men from families with a 50% probability of carrying a mutation in a dominant prostate cancer susceptibility gene.[3]	110 men aged 50–72 years.	68% of men ≥50 years were screened for prostate cancer.	Greater number of relatives with prostate cancer.
	110 men aged 50–72 years.	68% of men ≥50 years were screened for prostate cancer.	Low score on the avoidance subscales of the Impact of Event Scale.[28]
Brothers or sons of men with prostate cancer.[29]	136 men aged 40–70 years (72% were African American men).	PSA	Greater number of relatives with prostate cancer.
		72% reported ever having a PSA test.	Older age.
		– 73% within 1 year.	Urinary symptoms.
		– 23% 1–2 years ago.	71% reported their physician had spoken to them about prostate cancer screening.
		– 4% >2 years ago.
		DRE
		90% reported ever having had a DRE.
		– 60% within 1 year.
		– 23% 1–2 years ago.
		– 17% >2 years ago.
Unaffected men with and without a first-degree relative with prostate cancer.[30]	166 men aged 40–80 years (83 men with a first-degree relative; 83 men with no family history).	PSA	Family history of prostate cancer.
		First degree-relative: 72% reported ever having had a PSA test.	Greater perceived vulnerability to developing prostate cancer.
		No family history: 53% reported ever having had a PSA test.
French brothers or sons of men with prostate cancer.[31]	420 men aged 40–70 years.	PSA	Younger age.
		88% adhered to annual PSA screening.	Greater number of relatives with prostate cancer.
			Increased anxiety.
			Married.
			Higher education.
			Previous history of prostate cancer screening.
Unaffected African American men participating in a hereditary prostate cancer study and data from the 1998 and 2000 NHIS.[32]	Unaffected men aged 40–69 years (134 men with a family history of ≥4 men with prostate cancer; 5,583 men from 1998 NHIS [for DRE] including 683 African American men and 4,900 Caucasian men; 3,359 men from 2000 NHIS [for PSA] including 411 African American men and 2,948 Caucasian men).	PSA	Younger age.
		Family Study Cohort:	Fewer number of relatives with prostate cancer.
		45% reported ever having had a PSA test.
		African American men in NHIS:
		65% reported ever having had a PSA test.
		DRE
		Family Study Cohort:
		35% reported ever having had a DRE.
		African American men in NHIS:
		45% reported ever having had a DRE.

Quality of Life in Relation to Screening for Prostate Cancer Among Individuals at Increased Hereditary Risk

Concern about developing prostate cancer: Although up to 50% of men in some studies who were first-degree relatives of prostate cancer patients expressed some concern about developing prostate cancer,[5] the level of anxiety reported is typically relatively low and is related to lifetime risk rather than short-term risk.[3,5] The concern is also higher in men who are younger than their first-degree relative was at the time when their prostate cancer was diagnosed.[5] First-degree relatives who were unmarried worried more about developing prostate cancer than did married men.[5] Men with higher levels of concern about developing prostate cancer also had higher estimates of personal prostate cancer risk and a larger number of relatives diagnosed with prostate cancer.[5] In a Swedish study, only 3% of the 110 men surveyed said that worry about prostate cancer affected their daily life “fairly much,” and 28% said it affected their daily life "slightly."[3]

Baseline distress levels: Among men who self-referred for free prostate cancer screening, distress, both general and prostate cancer–related, did not differ significantly between men who were first-degree relatives of prostate cancer patients and men who were not.[33] Men with a family history of prostate cancer in the study had higher levels of perceived risk. In a Swedish study, male first-degree relatives of prostate cancer patients who reported more worry about developing prostate cancer had higher Hospital Anxiety and Depression Scale (HADS) depression and anxiety scores than men with lower levels of worry. In that study, the average HADS depression and anxiety scores among first-degree relatives was at the 75^th percentile. Depression was associated with higher levels of personal risk overestimation.[3]

Distress experienced during prostate cancer screening: A study measured the anxiety and general quality of life experienced by 220 men with a family history of prostate cancer while undergoing prostate cancer screening with PSA tests.[29] In this group, 20% of the men experienced a moderate deterioration in their anxiety scores, and 20% experienced a minimal deterioration in health-related quality of life (HRQOL). The average period between assessments was 35 days, which encompassed PSA testing and a wait for results that averaged 15.6 days. Only men with normal PSA values (4 ng/mL or less) were assessed. Factors associated with deterioration in HRQOL included being aged 50 to 60 years, having more than two relatives with prostate cancer, having an anxious personality, being well-educated, and having no children presently living at home. These authors stress that analysis of the impact of screening on first-degree relatives should not rely solely on mean changes in scores, which may “mask diversity among responses, as illustrated by the proportion of subjects worsening during the screening process.” Given that these were men receiving what was considered a normal result and that a subset of men experienced screening-associated distress, this study suggests that interventions to reduce screening-related distress may be needed to encourage men at increased hereditary risk to comply with repeated requests for screening.

A study in the United Kingdom assessed predictors of psychological morbidity and screening adherence in first-degree relatives of men with prostate cancer participating in a PSA screening study. One hundred twenty-eight first-degree relatives completed measures assessing psychological morbidity, barriers, benefits, knowledge of PSA screening, and perceived susceptibility to prostate cancer. Overall, 18 men (14%) scored above the threshold for psychiatric morbidity, consistent with normal population ranges. Cancer worry was positively associated with health anxiety, perceived risk, and subjective stress. However, psychological morbidity did not predict PSA screening adherence. Only past screening behavior was found to be associated with PSA screening adherence.[34]

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