Differences in ornithine decarboxylase and androgen receptor allele frequencies among ethnic groups.

Recent evidence suggests that the A allele of the ornithine decarboxylase (ODC) gene is a genetic risk factor for prostate cancer. ODC is a target gene of the highly polymorphic androgen receptor (AR) gene, short alleles of which have been associated in some studies with increased prostate cancer risk. We determined ODC allele frequencies and distribution of AR alleles in American Caucasians, African-Americans, Hispanics, Europeans, and Africans. The frequency of the ODC A allele varied from 0.183 (Hispanics, Europeans) to 0.415 (Africans) with American Caucasian and African-Americans having intermediate values. The mean number of CAG repeats in the AR gene varied from 19.8 (African-Americans) to 25.1 (Hispanics). It is possible that ethnic differences in risk alleles for ODC and AR may account for some of the ethnic variation in prostate cancer risk.

Prevalence and patterns of self-initiated nutritional supplementation in men at high risk of prostate cancer.

OBJECTIVE: To define the prevalence and patterns of self-initiated herbal and vitamin supplementation among men at high risk of developing prostate cancer, as there is increasing public awareness of prostate cancer screening, risk-factor assessment and prevention, leading to increasing interest in the use and systematic study of nutritional therapies for prostate cancer prevention. SUBJECTS AND METHODS: Since 1996 our institution has prospectively maintained a prostate cancer-risk registry through its Prostate Cancer Risk Assessment Program (PRAP). Eligibility includes African-American men, any man with at least one first-degree relative or two or more second-degree relatives with prostate cancer, or men who tested positively for the BRCA1 gene mutation. A 420-item self-administered questionnaire was completed and included the use of nutritional supplements and complementary therapies. We divided men into groups who used supplements to lessen their cancer risk and those who did not. The prevalence and patterns of use were evaluated and the two groups then compared for differences in demographic, socio-economic and risk-perception variables. RESULTS: In all, 345 high-risk men were enrolled in the PRAP over a 5-year period. Data on the use of dietary or herbal supplements were available on 333 men (97%), of whom over half (170) reported taking one or more supplements to prevent prostate cancer. Supplement use was divided into eight categories, including vitamins, minerals, extracts from fruits/seeds, organic compounds, flowers/bulbs, leaves/bark, roots, or animal products. Most commonly used for self-initiated chemoprevention were vitamins (95%), minerals (28%), and fruit/seed extracts (18%). More than a quarter of men (27%) took three or more agents. Men taking proactive preventative measures were statistically more likely to be Caucasian and aged > 60 years (P < 0.05). African-Americans were less likely to self-initiate preventative steps. Men taking supplements tended to return more often for follow-up and participate in PRAP longer, while those not taking supplements tended to earn less and report less self-perceived risk. CONCLUSIONS: A significant proportion of men at risk of developing prostate cancer initiate measures they perceive to reduce their risk. Although the chemopreventative efficacy of many of these supplements remains unsubstantiated, they are widely perceived by the public to reduce the risk of developing prostate cancer. These data provide an insight into patient perceptions and misconceptions of chemopreventative strategies, and may help to refine recruitment efforts in multi-institutional prostate cancer prevention trials.

Plasma levels of IGF-1, IGF-2, and IGFBP-3 in white and African-American men at increased risk of prostate cancer.

OBJECTIVES: To further investigate the relationship between the plasma levels of insulin-like growth factor-1 (IGF-1), insulin-like growth factor-2 (IGF-2), insulin-like growth factor binding protein-3 (IGFBP-3), growth hormone, testosterone, and demographic factors, particularly race, within a group of men at increased risk of prostate cancer development. METHODS: Enzyme-linked immunosorbent assays or an immunosorbent assay was used to quantitate the plasma levels of IGF-1, IGF-2, IGFBP-3, growth hormone, and testosterone. The study group consisted of 169 men (85 African-American, 84 white) aged 35 to 69 years, with no personal history of prostate cancer, but having at least one first-degree relative diagnosed with the disease, unless they were African-American. The relationships between the plasma levels and the categorical covariates were assessed using the nonparametric Wilcoxon test and between the continuous variables using Spearman's correlation coefficient. RESULTS: The mean plasma levels of IGFBP-3 were significantly lower in African-American (2657 ng/mL) than in white (2965 ng/mL) men (P = 0.0062). The plasma levels of IGF-2 were also lower in the African-American (503.5 ng/mL) than in the white (549.1 ng/mL) men (P = 0.0084). Overall, the IGF-1 plasma levels correlated positively with the IGF-2, IGFBP-3, and growth hormone levels and the IGF-2 plasma levels correlated negatively with the testosterone levels. CONCLUSIONS: Our results demonstrate that lower plasma levels of IGFBP-3 and IGF-2 are associated with race in a population of men at increased risk of developing prostate cancer. The ability of these markers to predict earlier disease onset is currently under investigation.

Psychological and screening profiles of first-degree relatives of prostate cancer patients.

The purpose of the present study was to systematically compare the psychological and screening profiles of first-degree relatives (FDRs) of prostate cancer patients versus non-FDRs. FDRs (n = 56) and non-FDRs (n = 100), recruited through prostate cancer index cases and newspaper advertisements, completed questionnaires via mail. FDRs reported feeling at greater risk for prostate cancer, estimated that they were at higher average lifetime risk for the disease, agreed more strongly that prostate cancer is inherited, and that less can be done to prevent the development of the disease. Increased age, but not FDR status, was associated with more frequent screening behavior. Taken together, the results indicate that FDRs are characterized by greater perceived vulnerability to prostate cancer and lower expectations about disease prevention. Yet, they are no more likely to be screened than non-FDRs. These findings underscore the importance of developing, and evaluating, evidence-based health communication protocols to promote screening adherence among at-risk patients.

Quality of life study in prostate cancer patients treated with three-dimensional conformal radiation therapy: comparing late bowel and bladder quality of life symptoms to that of the normal population.

PURPOSE: The goals of this study were twofold. First, differences were quantified for symptoms that impact bowel and bladder quality of life (QOL) in prostate cancer patients treated with three-dimensional conformal radiotherapy (3DCRT) alone to the prostate vs. whole pelvis with prostate boost. Second, bowel and bladder QOL measures for these patients were compared to those of the normal population of men with a similar age distribution. MATERIAL AND METHODS: Two health status surveys evaluating bowel and bladder functioning, along with the AUA Symptom Problem Index and the BPH Impact Index, were mailed to 195 prostate cancer patients treated with 3DCRT between 12/92 and 11/95 at Fox Chase Cancer Center by a single clinician (GH). No patient received hormonal management as part of his treatment. Ninety-five patients had pretreatment PSA levels <10 ng/ml, T1/T2A tumors with Gleason scores 2-6, and no perineural invasion. They were treated to the prostate alone and are referred to as Group I. The remaining 100 patients had one or more of the following characteristics: pretreatment PSA levels > or =10 ng/ml, T2B/T3 tumors, Gleason scores 7-10, or perineural invasion. These patients were treated to the whole pelvis followed by a boost to the prostate and are referred to as Group II. Frequencies were tabulated, and differences in percentages for the two groups were evaluated using the two-tailed Fisher's Exact Test. Overall percentages were compared to those for equivalent measures reported by Litwin (1999) based on a normal population of men with a mean age of 73 years (range 47-86). Comparisons to the normal population were also evaluated using two-tailed Fisher's Exact p values. RESULTS: The mailing yielded a high response rate of 71% (n = 139, 66 in Group I and 73 in Group II). The mean age was 67 (range 49-82), and the median ICRU dose levels for Groups I and II were 73 and 76 Gy, respectively. Responses relating to bladder symptoms were similar for Groups I and II, except for the degree of bother associated with trouble in urination over the last month. Percentages for no bother at all were 66% and 56% for Groups I and II, respectively. Observed differences in bowel functioning related to rectal urgency over the past year (22% vs. 40% for Groups I and II, p = 0.03), the use of pads for protection against bowel incontinence (0% vs. 10% for Groups I and II, p = 0.01), and bowel satisfaction (88% vs. 72% for Groups I and II, p = 0.03). There was no significant difference in the degree of bother bladder symptoms cause men treated with radiotherapy as compared to men without cancer. Few patients reported bowel dysfunction bother as a big problem, but patients do tend to have more very small to moderate bother from bowel dysfunction than the normal population (55% vs. 33%, p < 0.001). CONCLUSION: This is the first long-term study of QOL in men treated with high-dose 3DCRT for prostate cancer. It demonstrates that these men enjoy QOL related to bladder function similar to that of the normal population. Few patients report bother from bowel symptoms as a big problem but tend to have more very small to moderate bother than the normal population. Treatment of prostate cancer patients to the whole pelvis may result in decreased QOL as defined by rectal urgency, the use of pads for bowel incontinence, and satisfaction with bowel functioning. However, regardless of field size, men are generally satisfied with their bowel and bladder functioning three to six years post treatment.

Racial differences in insulin-like growth factor binding protein-3 in men at increased risk of prostate cancer.

OBJECTIVES: To determine the overall plasma levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in a group of men at higher risk of prostate cancer development and to investigate the relationships between demographics and these levels, particularly with regard to race. METHODS: An enzyme-linked immunosorbant assay was used to quantitate plasma levels of IGF-1 and IGFBP-3. The study group consisted of 105 men (63 African American [AA], 42 white), aged 35 to 69 years, with no personal history of prostate cancer, but having at least one first-degree relative diagnosed with the disease, unless they were AA. Differences in plasma levels and categorical covariates were assessed using the nonparametric Wilcoxon test. Associations between plasma levels and the continuous variables were quantified using the nonparametric Spearman correlation coefficient. RESULTS: The mean plasma level of IGF-1 was not significantly different between AA (162.3 ng/mL) and white (172.1 ng/mL) men (P = 0.415). However, the mean plasma level of IGFBP-3 was lower in AA (2789 ng/mL) than in white (3216 ng/mL) men, and this decrease was highly significant (P = 0.0045). No correlation between IGFBP-3 plasma level and age was detected in the group as a whole, but an inverse relationship between IGF-1 plasma level and age was evident (P = 0.0079). CONCLUSIONS: Our results demonstrate that IGFBP-3 plasma levels are lower in AA men than in white men. Since IGFBP-3 can control IGF-1 bioavailability, the lowered IGFBP-3 could explain in part the increased risk of prostate cancer in AA men.

RTOG's first quality of life study--RTOG 90-20: a phase II trial of external beam radiation with etanidazole for locally advanced prostate cancer.

PURPOSE: To assess institutional and patient compliance with quality of life (QL) instruments in RTOG clinical trials. To assess feasibility of using the Functional Assessment Cancer Therapy (FACT), Sexual Adjustment Questionnaire (SAQ), and Changes in Urinary Function (CUF) QL instruments in a prostate clinical trial and to compare patient self-report of symptoms to medical professional ratings of the same symptoms using the RTOG acute toxicity rating scales. METHODS AND MATERIALS: Three self-assessment QL instruments, the FACT, the SAQ, and CUF, were to be administered to patients on a Phase II locally advanced prostate trial at specified time points. Specific instructions for both data managers and for patients on when, how, and why to fill out the questionnaires were included. RESULTS: Sixty-seven percent (24 out of 36) of patients accrued to RTOG 90-20 completed both the initial FACT and SAQ. Eighty-five percent completed FACT at end of RT and 73% at 3 months. Eighty-one percent completed SAQ at end of treatment, while 69% completed this form at 3 months. Compliance drops off thereafter. Seventy-five percent of patients who had their symptom of dysuria rated by a medical professional as 0 on the RTOG toxicity rating scale self-reported the same. Only 56% of patient self-reports on FACT regarding diarrhea were in agreement with the medical professional's RTOG rating of 0 toxicity. The measures were determined to be in moderate agreement when the patient evaluated a symptom as a 1 on the FACT and the medical professional rated the same symptom as a 0 on the RTOG toxicity rating scale. There was moderate agreement in 13% of patients with dysuria and 31% of patients with diarrhea. Low agreement occurred when the patient evaluated a symptom as a 2 or 3 on the FACT and the medical professional rated the same symptom as a 0 on the RTOG scale. Low agreement occurred in 13% of both patients reporting dysuria and diarrhea. Differences between how medical professionals and patients were able to rate erectile function make direct comparisons difficult, but the trend towards significant discrepancies is still noteworthy. CONCLUSIONS: Quality of life assessments are necessary and attainable in RTOG clinical trials. Compliance rates for both institutional and patient participation were acceptable at initial and 3 month follow-up. Reasons for noncompliance were predominantly institution related and not patient related. Strategies to address both institution and patient compliance have been developed and implemented within the RTOG. Serious disagreement between patient self-reports of symptoms on the FACT QL scale and medical professional ratings on the RTOG acute toxicity rating scales of the same symptoms was 13% at 3 months follow-up. This warrants continued use of QL self-assessments in clinical trials.