Association of prostate cancer risk and aggressiveness to androgen pathway genes: SRD5A2, CYP17, and the AR

BACKGROUND: The prostate is an androgen-regulated organ and polymorphisms in genes involved in testosterone synthesis, in particular, SRD5A2 (A49T and V89L variants), CYP17 (MspAI variant), and the AR (CAG, GGC repeats), represent candidate risk factors for prostate cancer incidence and aggressiveness. METHODS: We evaluated the relationship between these five polymorphisms and prostate cancer risk in a family-based case-control study (N = 920). Cases were diagnosed at major medical institutions in Cleveland Ohio, and Detroit Michigan, and their unaffected brothers were used as controls. Associations were investigated with regard to prostate cancer risk, and clinical characteristics at diagnosis (i.e., tumor stage/grade, age, family history). RESULTS: The SRD5A2 V89L variant was associated with an increased risk of prostate cancer (OR = 1.56, P = 0.02). This association was driven primarily by men diagnosed at an earlier age (OR = 2.35, P = 0.001), or with more aggressive disease (OR = 1.63, P = 0.06). None of the other variants exhibited noteworthy associations with disease. CONCLUSIONS: These findings suggest that the SRD5A2 V89L variant may influence risk of developing prostate cancer, especially among men with a younger age of diagnosis or more aggressive disease.     

Family history and the risk of prostate cancer

A case-control study was performed to estimate the relative risk of developing prostate cancer for men with a positive family history. Extensive cancer pedigrees were obtained on 691 men with prostate cancer and 640 spouse controls. Fifteen percent of the cases but only 8% of the controls had a father or brother affected with prostate cancer (P less than .001). Men with a father or brother affected were twice as likely to develop prostate cancer as men with no relatives affected. In addition, there was a trend of increasing risk with increasing number of affected family members such that men with two or three first degree relatives affected had a five and 11-fold increased risk of developing prostate cancer. Recognizing that 9-10% of U.S. men will develop prostate cancer in their lifetime, men with a family history of prostate cancer should be advised of their significantly increased prostate cancer risk and should undergo appropriate screening measures for this disease.     

Effect of treatment with 5-α reductase inhibitors on progression in monitored men with favourable-risk prostate cancer

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Finasteride (Proscar) and dutasteride (Avodart) are 5‐α reductase inhibitors (5‐ARIs) used to treat LUTS in men with benign prostatic enlargement. Because these drugs suppress androgens, the theory has been put forward that 5‐ARIs might prevent the development of prostate cancer. Careful analysis of two randomized controlled trials, however, showed that, in the clinical setting, this was not the case, and that these drugs can increase the occurrence of more aggressive high‐grade disease. Because of this, the U.S. Food and Drug Administration did not approve 5‐ARIs for the primary prevention of prostate cancer and notified healthcare professionals about a change in the ‘Warnings and Precautions’ for these drugs. Interest remains among some for using 5‐ARIs in men diagnosed with very low‐risk prostate cancer to delay the progression from clinically indolent disease to clinically significant disease requiring treatment. The present study investigated whether 5‐ARI use among men with very low‐risk prostate cancer in an active surveillance (AS) programme would reduce the number of cancers reclassified to clinically significant disease on surveillance biopsy. Our results do not support the use of 5‐ARIs for slowing or preventing cancer progression in men with low‐risk prostate cancer, but do suggest that men with very low‐risk prostate cancer who take 5‐ARIs for LUTS are unlikely to be at increased risk for the development of high grade disease during AS.

OBJECTIVE

• ? To determine whether 5‐α reductase inhibitor (5‐ARI) use delays cancer reclassification in an active surveillance (AS) cohort.

PATIENTS AND METHODS

• ? We performed a retrospective study of 587 men enrolled in an AS programme, who had no history of 5‐ARI use.
• ? Chi‐squared and t‐tests were used to compare characteristics of 5‐ARI users and non‐users.
• ? Univariable and multivariable proportional hazards models, treating 5‐ARI use as a time‐dependent covariate, were used to evaluate the influence of 5‐ARIs on the risk of a subsequent biopsy no longer meeting criteria for continued AS (i.e. reclassification).

RESULTS

• ? 5‐ARI use was initiated in 47 men while on AS.
• ? Men using 5‐ARIs had larger prostates and higher PSA levels at diagnosis.
• ? During 5‐ARI use, PSA levels and prostate volume deceased by mean values of 47% and 11%, respectively.
• ? Men using 5‐ARIs had a mean of 2.5 surveillance biopsies while on the drug. Reclassification occurred in 17% of 5‐ARI users compared with 31% of non‐users (P= 0.04).
• ? Multivariable models (adjusting for age, α‐blocker use, PSA level, %free PSA, PSA density, prostate volume and number/percent biopsy core involvement at diagnosis) showed nonsignificant risk reductions for reclassification in 5‐ARI users as determined by either tumour extent (hazard ratio [HR]= 0.37 (95% confidence interval [CI] 0.12 to 1.13), P= 0.08) or grade (HR = 0.8 (95% CI 0.25–2.59), P= 0.7).

CONCLUSION

• ? Treatment with 5‐ARIs did not significantly alter the outcome of biopsy reclassification by grade in men with very low‐risk prostate cancer.

     

Populations at high risk for prostate cancer

Although prostate cancer tends to be a slow-growing neoplasm affecting older men, there is clearly a subset of patients at high risk for developing early and possibly more aggressive disease. This group of high-risk patients includes men with a family history of prostate cancer and various histologic features such as PIN and ASAP identified on an initial biopsy. Black American men have a much higher risk of developing prostate cancer when compared with white men and especially Asian men. This finding may reflect both genetic and environmental factors. Screening men at increased risk of developing prostate cancer appears to be a logical strategy, especially in light of recent reports that suggest a benefit to aggressive treatment.     

Role of family history and ethnicity on the mode and age of prostate cancer presentation

BACKGROUND: This study was conducted to investigate the role of family history of prostate cancer and ethnic variation on age at diagnosis and the mode of prostate cancer presentation among a multiracial cohort of men in the Bronx and on Long Island. METHODS: A retrospective hospital-based study of 953 men (62% white, 24% African-American, 9% Hispanic, and 5% other ethnicities) with biopsy-confirmed prostate cancer diagnosed between 1991 and 1996. Data were collected between 1996 and 1998 using self-administered questionnaires that assessed age at diagnosis, ethnicity, family history of prostate cancer, and first indication of potential prostate cancer. RESULTS: Men with a family history of prostate cancer were diagnosed at an earlier mean age than those who lacked a family history (P<0.001). Prostate cancer patients with an affected father had a significantly lower mean age at diagnosis than those patients who indicated that at least one brother (but not their father) was affected (P<0.001). African-Americans reported a family history of prostate cancer more often than whites (P<0.01) and were younger at diagnosis (P<0.0001). Hispanic patients were less likely to be identified by screening and more likely to present with symptoms compared with whites (P<0.0001) and African-Americans (P<0.001). CONCLUSIONS: Men with an affected father were more likely to have disease diagnosed at an early age. The lower rates of presentation by prostate cancer screening of Hispanic men with prostate cancer suggests that increased surveillance may be warranted in this population.     

Screening for prostate cancer in high risk populations

PURPOSE: Black men and men with a family history of prostate cancer are at higher risk for this disease and may have an earlier age of onset. Consequently, screening at a younger age has been recommended for high risk men, however, there are limited data on actual screening results in young, high risk populations. MATERIALS AND METHODS: In men 50 years old or older we compared screening results in 1,224 black men, 1,227 men with a positive family history and 63 men who were both with those of 15,964 nonblack men with no known family history. In high risk men in their forties we also evaluated the percent with abnormal screening tests, the positive predictive value of screening tests, cancer detection rates and the prognostic features of tumors detected. RESULTS: In men 50 years old or older prostate cancer detection rates were 6.4% for controls compared with 10.3%, 10.5% and 17.5%, respectively, for the high risk groups. Among high risk men screened in their forties 8% had suspicious screening tests and approximately 55% who underwent a biopsy had cancer detected. Of tumors detected 80% were organ confined and all but 1 were of moderate Gleason grade 5 years old or older. Only 1 tumor (7%) fulfilled the published criteria for a possibly harmless cancer. CONCLUSIONS: Black men and men with a family history of prostate cancer are at a 75% to 80% higher risk for prostate cancer. On initial screening of high risk men in their fourth decade only 8% have positive screening tests; however, approximately 55% of these men have tumors, most of which are medically important with favorable prognostic features.     

A systematic review and meta-analysis of familial prostate cancer risk

OBJECTIVE: To identify published studies quantifying familial prostate cancer risks in relatives of prostate cancer cases and, by meta-analysis, obtain more precise estimates of familial risk according to the family history. METHODS: Thirteen case-control and cohort studies were identified which have reported risks of prostate cancer in relatives of prostate cancer cases. Pooled estimates of risk for various categories of family history were obtained by calculating the weighted average of the log relative risk (RR) estimates from studies. RESULTS: The pooled RR (95% confidence interval) in first-degree relatives was 2.5 (2.2-2.8). There was evidence that this was highest in relatives of cases diagnosed before age 60 years and that RRs declined with age. The risk for the few men with two affected relatives was increased 3.5-fold (2.6-4.8). RRs to sons of cases appeared to be lower than in brothers; a complete explanation of this observation is uncertain. CONCLUSION: Men with a family history of prostate cancer have a significantly greater risk of developing prostate cancer than those with no such history. Risks are greatest for relatives of cases diagnosed when young and those with more than one relative affected.     

Management of low (favourable)-risk prostate cancer

What's known on the subject? and What does the study add? Most men who are diagnosed with favourable‐risk prostate cancer undergo some form of active intervention, despite evidence that treatment will not improve health outcomes for many. The decision to undergo treatment after diagnosis is, in part, related to the inability to precisely determine the long‐term risk of harm without treatment. Nevertheless, physicians should consider patient age, overall health, and preferences for living with cancer and the potential side effects of curative treatments, before recommending a management option. This is especially important for older men, given the high level of evidence that those with low‐risk disease are unlikely to accrue any benefit from curative intervention. What is known on the subject: Over treatment of favourable‐risk prostate cancer is common, especially among older men. What does the study add: A review of the natural history of favourable‐risk prostate cancer in the context of choices for management of the disease. ? The management of favourable‐risk prostate cancer is controversial, and in the absence of controlled trials to inform best practice, choices are driven by personal beliefs with resultant wide variation in practice patterns. ? Men with favourable‐risk prostate cancer diagnosed today often undergo treatments that will not improve overall health outcomes. ? A shared‐decision approach for selecting optimal management of favourable‐risk disease should account for patient age, overall health, and preferences for living with cancer and the potential side effects of curative treatments.     

The potential role of cyclooxygenase-2 inhibitors and 5alpha-reductase inhibitors in the prevention of urologic conditions

Prevention of urologic cancer is a new field for urology. It focuses attention on men and women who may not be under the regular care of physicians and are without symptoms of disease. Although risk factors (eg, smoking in bladder cancer, family history or African-American ethnicity in prostate cancer, cryptorchid testes in testis cancer, Von Hippel-Lindau disease in renal cell carcinoma) can identify individuals at a greater risk for genitourinary malignancies, most patients have no risk factors except gender and age. Thus, developing public health recommendations that will have a major impact on these diseases will be challenging. Prevention strategies will be held to a higher standard of safety than traditional cancer treatment unless populations at a high risk for disease can be identified. It will be necessary for urologists to monitor the field of disease prevention because of the high frequency of urologic malignancies and the growing elderly population in the United States. Urologists are frequently providers for and confidants of this patient population and must be able to counsel these men and women about the benefits and risks of such prevention strategies.     

Hereditary prostate cancer: clinical aspects

PURPOSE: We review the current epidemiological and genetic knowledge regarding hereditary prostate cancer, and outline its clinical implications. MATERIALS AND METHODS: Published articles on hereditary prostate cancer were identified using the MEDLINE data base. RESULTS: A risk of prostate cancer, particularly early onset disease, is strongly affected by family history (number of relatives with prostate cancer and their age at diagnosis). A family history of prostate cancer increases the positive predictive value of prostate specific antigen testing and, hence, heredity should always be assessed when deciding whether to perform biopsies in a man with a prostate specific antigen level of 3 to 10 ng./ml. Epidemiological studies indicate that dominantly inherited susceptibility genes with high penetrance cause 5% to 10% of all prostate cancer cases, and as much as 30% to 40% of early onset disease. More than a half dozen chromosome loci that may comprise such genes have been mapped, but as of May 2002 no prostate cancer susceptibility gene of major importance had been cloned. Most likely, environmental factors and comparatively common variants of several other genes affect prostate cancer risk in families with or without multiple cases of the disease. On average, hereditary prostate cancer is diagnosed 6 to 7 years earlier than sporadic prostate cancer, but does not otherwise differ clinically from the sporadic form. As a consequence of the earlier onset, a greater proportion of men with hereditary prostate cancer die of the disease than those with nonhereditary prostate cancer. At present, the only clinically applicable measure to reduce prostate cancer mortality in families with hereditary disease is screening, with the aim of diagnosing the disease when it is still in a curable stage. CONCLUSIONS: Hereditary susceptibility is now considered the strongest risk factor for prostate cancer and has profound clinical importance. The genetic mechanism behind such susceptibility has turned out to be more complex than initially thought, and will probably not be completely understood for many years to come.     

A broader role for 5ARIs in prostate disease? Existing evidence and emerging benefits

5ARIs are recommended for men who have moderate‐to‐severe lower urinary tract symptoms (LUTS) and benign prostatic enlargement (BPE) secondary to benign prostatic hyperplasia. Studies have confirmed the utility of combining 5ARIs with alpha‐blockers; the MTOPS study showed that risk of overall clinical progression was significantly reduced after 4.5 years with combination therapy (finasteride/doxazosin) in comparison with either monotherapy, while the ongoing CombAT trial (dutasteride/tamsulosin) has for the first time shown benefit in improving symptoms for combination therapy over monotherapies within 12 months of treatment. Data also suggest roles for 5ARIs in prostate cancer. Several studies indicate that treatment with a 5ARI improves the performance of PSA testing for identifying men with prostate cancer, while the PCPT showed a significant reduction in the risk of developing prostate cancer with finasteride. However, widespread use of finasteride in this setting has been tempered by an apparent increase in high‐grade disease observed in the study. The ongoing REDUCE study will provide further insight into prostate cancer prevention with 5ARIs. 5ARI‐containing regimens may have utility as less aggressive treatment options for patients who only have rising PSA after definitive local therapy, and in patients with disease resistant to androgen deprivation therapy who have PSA progression. Current evidence therefore shows that 5ARIs are effective in treating LUTS/BPE and preventing disease progression, and may also have a role in the prevention of prostate cancer. The overlap between BPE and prostate cancer may allow a more unified approach to managing these conditions, with 5ARIs having a central role. Prostate 69: 895–907, 2009. © 2009 Wiley‐Liss, Inc.     

Familial risk of prostate cancer in Iceland

OBJECTIVE: To estimate the risk of prostate and other types of cancer among relatives of Icelandic men diagnosed with prostate cancer over a 5-year period. PATIENTS AND METHODS: The risk ratio (RR) was used to estimate the risk among relatives of 371 patients with prostate cancer, all of whom lived in Iceland and were diagnosed when alive over a 5-year interval (1983-7). Information on cancer incidence was obtained from the population-based Icelandic Cancer Registry, and information on families from a comprehensive genealogical database covering the population of Iceland. RESULTS: First-degree male relatives were at a 1.7-fold greater age-adjusted risk of prostate cancer (1832 men; 95% confidence interval, CI, 1.28-2.34). The risk was independent of proband's age at diagnosis. First-degree male relatives of patients who died from prostate cancer were at a statistically significantly greater risk of the disease (784 men; RR 2.17; 95% CI 1.34-3.53) and relatives of patients with incidental disease (T1a) were at a greater risk but not statistically significant so (261; RR 1.86; 95% CI 0.75-4.58). Female first-degree relatives were not at greater risk of breast cancer. The risk of kidney cancer was higher in first- and second-degree female relatives, with an RR (n, CI) of 2.50 (1780, 1.10-5.66) and 2.67 (5534, 1.04-6.81), respectively. The risk of kidney cancer was not statistically significantly greater in male relatives. CONCLUSION: Family history is a risk factor for prostate cancer in Icelandic men. The risk is potentially higher for relatives of patients who die from the disease. Female relatives are not at greater risk of breast cancer but they may be at greater risk of kidney cancer.     

Expectant management: an option for localized prostate cancer

Localized prostate cancer demonstrates tremendous heterogeneity in the natural history of the disease. To this end, although prostate cancer may be present histologically in nearly 30% of all men above the age of 50 y, the lifetime risk of developing clinically significant disease is 18% (one in six). Furthermore, the lifetime risk of dying from prostate cancer is less than 4%. Therefore, in order to avoid unnecessarily treating potentially insignificant prostate cancer, the concept of expectant management has been considered for this disease. In this brief review, we discuss the evolution of expectant management for men with localized prostate cancer.     

Male patients with diagnoses of both breast cancer and prostate cancer

Abstract: Recently cancer susceptibility syndromes have been characterized that suggest possible genetic linkages between breast cancer and prostate cancer within families. Despite these connections, male breast cancer and prostate cancer in an individual man has rarely been reported. The clinical features of 10 patients with both of these cancers are described here. One hundred sixty-one patients with male breast cancer were seen at the Dana-Farber Cancer Institute and Massachusetts General Hospital between 1977 and 2000. Of these, 10 were identified who also had prostate cancer. A retrospective review of records from these 10 patients was performed. Breast cancer preceded prostate cancer in eight of these men. The mean age of diagnosis of breast cancer was 65.7 years (range 47–72 years). Twenty percent had nodal involvement at diagnosis and two patients ultimately developed evidence of metastatic disease. The mean age of diagnosis of prostate cancer was 68.0 years (range 51–76 years) with a median prostate-specific antigen (PSA) level at diagnosis of 6 ng/ml (range 1.8–47.5 ng/ml). Seven patients had a family history of female breast cancer in a first-degree relative, while one had a family history of prostate cancer. At a median follow-up of 6.5 years from initial cancer diagnosis, one patient had died of metastatic breast cancer and another had died of metastatic prostate cancer. The clinical features and course of the breast cancers diagnosed in this series do not appear significantly different from those described for the general population of male breast cancer patients. In addition, these men do not appear to develop prostate cancer at an earlier age or more aggressive stage than the general population.     

Prevalence, treatment modalities and prognosis of familial prostate cancer in a screened population

PURPOSE: A family history of prostate cancer is an important risk factor for this disease. The clinical presentation and prognosis of familial disease remain uncertain. In this study these entities are evaluated in the first and second rounds of a screening program in The Netherlands. MATERIALS AND METHODS: Of all men randomized in the Rotterdam section of the ERSPC, 19,970 men were eligible for screening. Information regarding the family history was obtained by a self-administered questionnaire at baseline. RESULTS: In the prevalence screen the cancer detection rate in 1,364 men (7.1%) with a positive family history was 7.7% (106 cancers in 1,364 screened men with a positive family history) while the positive predictive value of the biopsies was 32.2% (154 cancers of 532 biopsies). In 12,803 sporadic cases the detection rate was 4.7% and the positive predictive value was 23.6% (p <0.0001 and 0.003, RR 1.63). No clinicopathological differences were found in the 1,559 men diagnosed in the first and second rounds. The overall biochemical-free survival rate after a mean followup of 56.8 months (range 0 to 129.9) was 76.8%, and was not significantly different in familial and sporadic cases (p = 0.840). These findings were consistent for the specific treatment modalities as well. CONCLUSIONS: Although screened men 55 to 75 years old with a father or a brother having prostate cancer themselves are at a substantially greater risk for the disease, the clinical presentation, treatment modalities and prognosis by biochemical progression are not different compared to sporadic cases.     

The effects of 5alpha-reductase inhibitors on the natural history, detection and grading of prostate cancer: current state of knowledge

PURPOSE: The Prostate Cancer Prevention Trial (PCPT) showed that the 5alpha-reductase inhibitor (5ARI) finasteride significantly decreased the 7-year period prevalence of prostate cancer vs placebo. However, Gleason score 7-10 tumors were significantly more common in the finasteride vs the placebo group. We considered data on the effects of 5ARIs on prostate cancer natural history and detection. MATERIALS AND METHODS: A detailed review was performed of the literature identified from the MEDLINE database examining the effects of 5ARIs on prostate cancer prevalence and tumor histopathology. RESULTS: In PCPT there were fewer biopsies performed for cause in the finasteride vs the placebo group and the proportion of high grade tumors in the treatment groups did not diverge with time. Given that finasteride has an effect on prostate specific antigen and prostate volume, which are key factors in triggering prostate biopsies, they may be significant confounders of Gleason score results. Prostate shrinkage in the finasteride treated group may minimize biopsy sampling error. Furthermore, histological studies have shown that 5ARIs have a significant effect on prostate architecture, which can make the interpretation of prostate specimens in men treated with 5ARIs difficult. Further evaluation of PCPT findings will help determine the true nature of these observations. CONCLUSIONS: 5ARIs decrease the risk of prostate cancer but also alter the detection of disease through effects on prostate specific antigen, and prostate volume and histology. The weight of evidence suggests an artifactual effect of finasteride on Gleason grading in the PCPT. The role of 5ARIs for prostate cancer chemoprevention needs further examination before it can be considered for wide recommendation.     

Benign prostatic hyperplasia: racial differences in treatment patterns and prostate cancer prevalence

Study Type – Prevalence (prospective cohort with good follow‐up) Level of Evidence 1b What’s known on the subject? and What does the study add? Previous studies evaluating racial differences in BPH treatment and outcomes have concluded that more attention in the management of lower urinary tract symptoms should be directed at African Americans. Although the relationship between BPH and the development of prostate cancer is inconclusive, longitudinal studies have indicated racial disparities in the incidence of prostate cancer. This is the first long‐term follow‐up study in a BPH population to assess the incidence of prostate cancer among African American and Caucasian men under “real‐world” clinical practice circumstances. This study suggests that African Americans with BPH have a much greater risk of developing prostate cancer than similar Caucasian men, highlighting the need for education, prevention and early detection.

OBJECTIVE

? To compare prostate cancer, prostate‐related surgery and acute urinary retention rates, as well as associated healthcare resource use over 11 years in African American and Caucasian men with benign prostatic hyperplasia (BPH).

PATIENTS AND METHODS

? The BPH‐related medical and surgical charges and events were determined for 398 African American men and 1656 Caucasian men followed for a mean of 10.2 years within a health maintenance organization. ? Racial differences in clinical outcomes were evaluated using time‐to‐event analysis, stratifying results by baseline prostate‐specific antigen (PSA) values.

RESULTS

? Risk of a prostate cancer diagnosis was 2.2 times greater in African American than Caucasian men (95% CI 1.48–3.35, P < 0.001) in analyses adjusting for serum PSA level. ? Although African Americans were more likely to receive medical therapy for symptoms of BPH than Caucasians (43.5% vs 37.2%, respectively; P= 0.029), there were no clinically meaningful differences with respect to subsequent acute urinary retention or BPH‐related surgery between them, or BPH‐related medical charges (US $407 vs US $405 per month).

CONCLUSION

? As evidenced by this analysis of ‘real‐world’ clinical practice, African Americans with BPH have a much greater risk of developing prostate cancer than similar Caucasian men highlighting the need for education and early detection in this population.     

Current age and race adjusted prostate specific antigen threshold values delay diagnosis of high grade prostate cancer

PURPOSE: Age specific prostate specific antigen ranges have been advocated to increase the predictive value of prostate specific antigen based on increases that occur with aging. We suggest that prostate specific antigen is not a dichotomous biomarker and age specific reference ranges delays the diagnosis of high grade prostate cancer in older and black American men. MATERIALS AND METHODS: Using the Prostate Cancer Prevention Trial risk calculator we evaluated the impact of age on the risk of high grade prostate cancer in white and black men. We created a hypothetical population of men by standardizing risk variables, including negative family history, normal digital rectal examination and no history of negative biopsy. Results were compared in the 2 populations using 5-year age increments from ages 55 to 75 years and increasing prostate specific antigen. RESULTS: Increasing age was associated with a higher risk of high grade prostate cancer in white and black men. The risk of high grade prostate cancer in a black man was twice that in a white man with the same prostate specific antigen at all prostate specific antigen values. CONCLUSIONS: Age specific and race specific prostate specific antigen ranges are flawed. Many patients who would not be considered for biopsy based on these prostate specific antigen ranges are at significant risk for high grade prostate cancer. The risk of high grade prostate cancer in black men is twice that in white men. Risk assessment in black men and older men is necessary to diagnose high grade prostate cancer when treatment can be effective.     

青岛市区前列腺癌与家族史、婚育史关系的病例对照研究

目的了解青岛市区前列腺癌发病与家族史及婚育史的关系,为前列腺癌的科学防治提供理论依据。方法在青岛市市立医院开展一项病例对照研究（1∶2配对）,匹配条件为年龄组、性别、民族和居住地类型相同。调查以面谈为主,辅以调查病历记录,采用条件Logistic回归法分析数据。结果以其他疾病作为对照,家族中有恶性肿瘤患者前列腺癌的风险是无亲属患恶性肿瘤者的2.58倍;首次遗精年龄≤14岁者患前列腺癌的风险是≥18岁者的2.27倍;而首次性交年龄在25～30岁者是前列腺癌的保护因素,OR=0.76;35岁以前性生活频率≥4次/周与手淫≥3次/周者患前列腺癌风险明显增高,OR分别为2.57、2.30。结论肿瘤家族史、首次遗精年龄较早、35岁前性生活频繁、手淫频繁均为前列腺癌的危险因素。