| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Departments of Epidemiology [C. H. B., A. L. P., L. H. K.], Medicine [A. M. B., D. L. T.], Urology [B. R. K., C. A. V.], and Pathology [R. D., M. J. B.], University of Pittsburgh, Pittsburgh, Pennsylvania 15261; Department of Medicine, Tobago Regional Hospital, Scarborough, Tobago, Trinidad & Tobago [A. L. P.]; and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15260 [R. D., A. M. B., M. J. B., D. L. T., L. H. K.]
| Abstract |
|---|
|
|
|---|
4 ng/ml) or abnormal DRE were offered an ultrasound-guided sextant biopsy of the prostate gland. Men (2484), ages 4079 years, underwent prostate cancer screening between September 1997 and June 2001. Mean age was 55.9, SD was 10.6 years, and median was 54 years. Mean serum PSA was 14.8 ng/ml, SD was 376 [excluding 4 values
2 SD above the mean (1,112, 1,317, 1,818, and 18,330 ng/ml) mean PSA was 5.5 ng/ml and SD was 29.6], and median PSA was 1.2 ng/ml. Elevated PSA and/or abnormal DRE were observed in 31% (759 of 2484) overall, and in age groups 4049 (87 of 843, 10%), 5059 (201 of 729, 28%), 6069 (262 of 584, 45%), and 7079 (209 of 328, 64%). Of 681 men biopsied, 259 (38%, or 10% of the 2484 screened) were diagnosed with prostate cancer. Age-specific rates of screening detected prostate cancer were: 1%, ages 4079 years; 7%, ages 5059 years; 18%, ages 6069 years; and 28%, ages 7079 years. These screening results indicate a very high screening-detected prevalence of prostate cancer in this population of West African descent. These data support the hypothesis that populations of African descent share genetic and/or lifestyle factors that contribute to their elevated risk for prostate cancer. | Introduction |
|---|
|
|
|---|
Established risk factors for prostate cancer include age, ethnicity, family history of prostate cancer, and high-fat or meat diet (2) . Other factors suspected include hormone metabolism, (3 , 4) vitamin D metabolism, (5) and a few occupational exposures (6) . The relationships of a number of candidate genes to prostate cancer are under investigation with most published results limited to Caucasian populations (7 , 8) . The reasons for the higher risk for prostate cancer among African Americans are unknown.
Until recently, there has been little solid prevalence, incidence, or mortality data for populations of African descent outside the United States, although data published a few years ago in an annual summary of worldwide data suggested high rates of prostate cancer mortality in Martinique and Trinidad & Tobago (9) . Glover et al. (10) reported high rates of prostate cancer incidence in the predominantly Afro-Caribbean population of Jamaica. Data regarding screening parameters and prevalence of prostate cancer in populations of African descent in the United States are sparse (11 , 12) and virtually absent in other populations of African descent. However, a recent publication has estimated prostate cancer prevalence for 1994 among African Americans and Caucasians using a model based on incidence and survival functions calculated from the Connecticut Tumor Registry, 19401993, and applied to the SEER 19731993 populations. The prevalence proportion ranged from 7 of 100,000, ages 4044 years, to 9,725 of 100,000, ages 7579 years, in Caucasians, compared with 14 of 100,000, ages 4044 years, to 10,945 of 100,000, ages 7579 years, in African Americans (13) .
We hypothesize that risk for prostate cancer is high among populations of African descent living in diverse environments. If so, this would lead us to hypothesize that populations of African descent share genetic and/or lifestyle factors that increase risk for prostate cancer.
On the island of Tobago, Trinidad & Tobago, we are conducting a population-based, longitudinal study of prostate cancer in the male population ages 4079 years. In this report, we present data from the initial cross-sectional screening using serum PSA and DRE.
| Materials and Methods |
|---|
|
|
|---|
Recruitment.
The recruitment goal was 4000 men, 80% of the male population of Tobago, ages 4079 years. Currently, >3000 men are enrolled. Recruitment has been the result of word of mouth, informing by healthcare workers at the hospital and health centers, informing by private physicians, posters, flyers, public service announcements, and public presentations by oncologists and urologists from Trinidad and the United States.
Informed Consent.
Consent was obtained using forms and procedures approved by the Institutional Review Boards of University of Pittsburgh Institutional Review Board and the Tobago Ministry of Health.
Data Collection.
Data were collected by locally resident study staff at the study office located at the Tobago Regional Hospital. Data collected included ethnicity, education, occupation, smoking, medical history, personal and family cancer history, vasectomy, prostate symptoms, health screening history, alcohol intake, detailed occupational history, and height, weight, waist, and hip measurements.
Biological Sample Collection.
A 15-ml plain vacutainer of peripheral blood was drawn from fasting subjects. Aliquots of serum were frozen at -20°C for later measurement of PSA.
DRE.
A systematic DRE was performed by a physician trained according to the study protocol. This exam was scheduled after the blood draw to avoid an artifactual increase in serum PSA that may follow digital manipulation of the gland.
PSA Measurement.
Serum PSA levels were measured at the University of Pittsburgh Central Pathology Laboratory using the automated Microparticle Enzyme Immunoassay, Abbot AxSYM PSA assay (Abbott Laboratories, Abbott Park, IL).
Criteria for Referral for Prostate Biopsy.
Subjects were referred to the Tobago Regional Hospital for biopsy if the DRE was abnormal (except for simple enlargement without palpably abnormal areas) or if serum PSA was elevated (
4.0 ng/ml).
Prostate Biopsy.
Prostate biopsies were performed by urologists or by surgeons trained by urologists from the University of Pittsburgh Medical Center. Trans-rectal ultrasound guided biopsy was performed using an 18 gauge, 21-cm spring-loaded biopsy needle (Boston Scientific, Natick, MA). Sextant biopsies were obtained according to a standard protocol.
Prostate Pathology.
The formalin preserved specimens were stored at room temperature and shipped to the University of Pittsburgh for histopathological examination. The specimens were examined for presence or absence of high-grade prostatic intraepithelial neoplasia, presence or absence of cancer, Gleason score of cancer, location of cancer, and perineural invasion.
Data Analysis.
Age-specific prevalence rates (per 100 screened men) were calculated. Age-adjusted rates/100 and SE/100 were calculated by direct standardization (15)
based on the age distribution (5079 years) of the 1970 United States standard million population (1)
. Positive predictive value of the screening tests was calculated as number of men diagnosed with prostate cancer divided by the number of men with abnormal DRE and/or elevated PSA who underwent biopsy. All statistical calculations were performed using SPSS 10.0 for Windows (SPSS Inc., Chicago, IL).
| Results |
|---|
|
|
|---|
The serum PSA range was 0.118,330 ng/ml. Mean serum PSA was 14.8 ng/ml and SD was 376. After excluding 4 values
2 SD above the mean [1,112, 1,317, 1,818, and 18,330 ng/ml], mean PSA was 5.5 ng/ml, SD was 29.6, median PSA was 1.2 ng/ml, and range was 0.1602 ng/ml.
Elevated serum PSA levels (
4 ng/ml) were observed in 452 of 2437 men (19%), ranging from 2% of men, ages 4049 years, to 53% of men, ages 7079 years. DRE was abnormal in 514 of 2074 men (25%). Frequency of abnormal DRE increased across age groups from 11 to 48%. Abnormal screening results (PSA
4 ng/ml and/or abnormal DRE) are shown in Table 1
. PSA and/or DRE were abnormal in 759 of 2484 men (31%). Thus, a high proportion of the screened men was referred for biopsy: 10% of men, ages 4049 years; 28%, ages 5059 years, 45%, ages 6069 years; and 64%, ages 7079 years.
|
The high prevalence rate reported above reflects not only the high rate of abnormal screening results but also a high-positive predictive value for an abnormal screen: 12% of biopsied men ages 4049 years were diagnosed with prostate cancer; 27%, ages 5059 years; 45%, ages 6069 years; and 53%, ages 7079 years (Table 1)
.
Among 123 men reporting family history of prostate cancer, 117 reported one relative, 5 reported two relatives, and 1 reported three relatives with prostate cancer. The distribution of relatives included 78 fathers, 65 brothers, 3 half-brothers, 8 uncles, and 2 grandfathers. Thirteen (10.6%) of 123 men reporting family history of prostate cancer were diagnosed with prostate cancer, compared with 246 (10.4%) men diagnosed with prostate cancer among 2361 men not reporting family history of prostate cancer.
Eight percent of men reported that a physician had told them they had benign prostatic hypertrophy. Waking to urinate more than once/night was reported by 51% of men (62% of men ages 5079 years). The rate rose steadily from 33% among men ages 4049 years to 86% among men ages 7079 years. Within each age group, the rate was similar in cases and noncases.
| Discussion |
|---|
|
|
|---|
|
The United States population in the previously mentioned study (18) was screened in 19911992, a period during which the incidence of prostate cancer was rising sharply (1) , reflecting increasing use of PSA testing. Thus, some prostate cancer cases may have been removed from this United States population by prior screening. However, 19% of the Tobago men, ages 5079 years, reported a prior PSA test, suggesting that some level of screening had also been available in this Tobago population.
Both the United States (18)
and the Tobago populations were self-referred. The Tobago population was recruited primarily by word of mouth. The United States population was recruited by advertisement. Among the United States population, 53% reported symptoms of prostatism. Sixty-two percent of Tobago men, ages 5079 years, reported waking to urinate two or more times/night. If self-referral bias were to have a strong effect, one would have expected higher prostate cancer rates among men recruited earlier in the study compared with later. As shown in Fig. 2
, this was somewhat true, particularly in the oldest age group among whom symptoms were more likely to be related to prostate cancer. Compared with the age-standardized rate of screening-detected prostate cancer (15.1%) among men ages 5079 years in the total screened group, the rate based on the men recruited only in 20002001 was somewhat lower, 13.4%. Even after deflating the conservative 13.4% rate by the ratio of the biopsy rates in the two populations, the even more conservative estimate of the age-standardized rate of screening-detected prostate cancer of 10.3% is still almost 3-fold higher than in the United States population, Richie et al. (18)
.
|
One of the known risk factors for prostate cancer is ethnicity, i.e., African descent, although we do not know how this risk is mediated. One hypothesis is that genetic factors contribute to the high risk for prostate cancer among populations of African origin. If the Caucasian admixture rate in the Tobago population is indeed low, then this population may carry a higher burden of high-risk genes of African descent than the more admixed populations in the United States.
In conclusion, compared with Caucasian and other populations, the higher incidence of prostate cancer observed in populations of African descent, African Americans (1) and Jamaicans (10) , and the very high screening-detected prevalence of prostate cancer observed in this study among Tobagonians support the hypothesis that these populations share ancestral genetic factors that increase susceptibility to prostate cancer. However, the variability in risk across these populations of African descent suggests an important influence of unknown environmental/lifestyle factors acting on prostate cancer risk in these susceptible populations.
| Footnotes |
|---|
1 This study was supported, in part, by funding or in-kind services from the Division of Health and Social Services, Tobago House of Assembly, the University of Pittsburgh Cancer Institute, U.S. Department of Defense, contract DAMD17-99-1-9015, and National Cancer Institute Grant R01 CA84950. ![]()
2 To whom requests for reprints should be addressed, at Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, A542 Crabtree Hall, 130 DeSoto Street, Pittsburgh, PA 15261. Phone: (412) 624-3467; Fax: (412) 624-7397; E-mail: bunkerc+{at}pitt.edu ![]()
3 Present address: Department of Urology, University of Iowa, Iowa City, IA 52242. ![]()
4 The abbreviations used are: SEER, Surveillance, Epidemiology, and End Results; PSA, prostate-specific antigen; DRE, digital rectal exam. ![]()
Received 8/16/00; revised 4/ 1/02; accepted 4/22/02.
| References |
|---|
|
|
|---|
This article has been cited by other articles:
![]() |
S. J. Prior, S. M. Roth, X. Wang, C. Kammerer, I. Miljkovic-Gacic, C. H. Bunker, V. W. Wheeler, A. L. Patrick, and J. M. Zmuda Genetic and environmental influences on skeletal muscle phenotypes as a function of age and sex in large, multigenerational families of African heritage J Appl Physiol, October 1, 2007; 103(4): 1121 - 1127. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. S. Consedine, D. Horton, T. Ungar, A. K. Joe, P. Ramirez, and L. Borrell Fear, Knowledge, and Efficacy Beliefs Differentially Predict the Frequency of Digital Rectal Examination Versus Prostate Specific Antigen Screening in Ethnically Diverse Samples of Older Men American Journal of Men's Health, March 1, 2007; 1(1): 29 - 43. [Abstract] [PDF] |
||||
![]() |
M. L. Freedman, C. A. Haiman, N. Patterson, G. J. McDonald, A. Tandon, A. Waliszewska, K. Penney, R. G. Steen, K. Ardlie, E. M. John, et al. From the Cover: Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men PNAS, September 19, 2006; 103(38): 14068 - 14073. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. S. Consedine, A. H. Morgenstern, E. Kudadjie-Gyamfi, C. Magai, and A. I. Neugut Prostate cancer screening behavior in men from seven ethnic groups: the fear factor. Cancer Epidemiol. Biomarkers Prev., February 1, 2006; 15(2): 228 - 237. [Abstract] [Full Text] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Cell Growth & Differentiation |