Prostate cancer has the highest prevalence of any nonskin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating androgens will develop microscopic prostate cancer if they live long enough. This review is a contemporary and comprehensive, literature-based analysis of the putative risk factors for human prostate cancer, and the results were presented at a multidisciplinary consensus conference held in Crystal City, Virginia, in the fall of 2002. The objectives were to evaluate known environmental factors and mechanisms of prostatic carcinogenesis and to identify existing data gaps and future research needs. The review is divided into four sections, including 1) epidemiology (endogenous factors [family history, hormones, race, aging and oxidative stress] and exogenous factors [diet, environmental agents, occupation and other factors, including lifestyle factors]); 2) animal and cell culture models for prediction of human risk (rodent models, transgenic models, mouse reconstitution models, severe combined immunodeficiency syndrome mouse models, canine models, xenograft models, and cell culture models); 3) biomarkers in prostate cancer, most of which have been tested only as predictive factors for patient outcome after treatment rather than as risk factors; and 4) genotoxic and nongenotoxic mechanisms of carcinogenesis. The authors conclude that most of the data regarding risk relies, of necessity, on epidemiologic studies, but animal and cell culture models offer promise in confirming some important findings. The current understanding of biomarkers of disease and risk factors is limited. An understanding of the risk factors for prostate cancer has practical importance for public health research and policy, genetic and nutritional education and chemoprevention, and prevention strategies.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.20408

Human prostate cancer risk factors.

BACKGROUND
The widespread use of prostate-specific antigen (PSA) screening has had a tremendous impact on all aspects of the management of prostate carcinoma. Although PSA-based screening has resulted in a stage migration to more organ-confined tumors at the time of diagnosis, and has been temporally associated with a decrease in prostate carcinoma mortality, PSA screening is imperfect. A recent analysis of results from the Prostate Cancer Prevention Trial (PCPT) has provided insight into the positive predictive value of PSA in the so-called “normal” range.

METHODS
The history of the discovery, initial studies, and subsequent widespread application of PSA screening is reviewed.

RESULTS
The application of PSA for screening preceded the development of current prostate biopsy techniques and an upper limit of normal was established without complete disease ascertainment. More recent modifications of PSA-based screening have been adopted clinically without sufficient validation. With current methods, overdiagnosis of clinically unimportant disease almost certainly occurs and high-grade, aggressive disease may not be detected sufficiently early to allow successful treatment.

CONCLUSIONS
To the authors' knowledge, the optimal upper limit of normal for PSA for prostate carcinoma screening is unknown. New biomarkers of disease are needed; these must be linked with disease prognosis and must be validated in rigorously designed clinical trials. Cancer 2004. © 2004 American Cancer Society.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.20480

Prostate-specific antigen: a review of the validation of the most commonly used cancer biomarker.

The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared with European-American men We tested the hypothesis that differences in tumor biology contribute to this survival health disparity Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients These tumors were matched on clinical variables We also evaluated 18 nontumor prostate tissues from seven African-American and 11 European-American patients The resulting datasets were analyzed for expression differences on the gene and pathway level comparing African-American with European-American patients Our analysis revealed a significant number of genes, eg, 162 transcripts at a false-discovery rate of <or=5% to be differently expressed between African-American and European-American patients Using a disease association analysis, we identified a common relationship of these transcripts with autoimmunity and inflammation These findings were corroborated on the pathway level with numerous differently expressed genes clustering in immune response, stress response, cytokine signaling, and chemotaxis pathways Several known metastasis-promoting genes, including autocrine mobility factor receptor, chemokine (C-X-C motif) receptor 4, and matrix metalloproteinase 9, were more highly expressed in tumors from African-Americans than European-Americans Furthermore, a two-gene tumor signature that accurately differentiated between African-American and European-American patients was identified This finding was confirmed in a blinded analysis of a second sample set In conclusion, the gene expression profiles of prostate tumors indicate prominent differences in tumor immunobiology between African-American and European-American men The profiles portray the existence of a distinct tumor microenvironment in these two patient groups

https://cancerres.aacrjournals.org/content/canres/68/3/927.full.pdf

Tumor Immunobiological Differences in Prostate Cancer between African-American and European-American Men

Hispanics living in the United States may face substantial adversity, given stresses of immigration and acculturation, low incomes, poor educational and occupational opportunities, inadequate access to health care, and exposure to discrimination. Despite these disadvantages, the Hispanic population often shows equal or better health outcomes when compared to non-Hispanic Whites, a trend that has puzzled researchers and has been referred to as the "Hispanic Paradox." Hispanics with non-U.S. nativity also tend to show better health than those born in the United States, although this advantage dissipates with increasing time spent in the United States. The current article discusses the Reserve Capacity Model (L.C. Gallo & K. A. Matthews, 2003) as a potential framework for understanding how psychosocial risk and resilient factors may contribute to health disparities associated with broad sociocultural factors, such as low socioeconomic status or minority ethnicity. In addition, we examine theory concerning features of the Hispanic culture that may enhance resilience (e.g., social resources, familism, religiousness; G. Marin & B. V. Marin, 1991) in the face of adverse circumstances. We summarize some of our recent work that has empirically tested effects of risk and resilient factors in Hispanic health in the contexts of prostate cancer and cardiovascular disease. We conclude by discussing future directions and opportunities for researchers interested in culture-specific resiliency factors in relation to health outcomes.

Resiliency in the face of disadvantage: do Hispanic cultural characteristics protect health outcomes?

Background: African-Americans are more likely than Caucasians to be diagnosed at an advanced stage of colorectal, lung, breast, cervical, and prostate cancers. This study explores if racial differences in stage at diagnosis can be explained by socioeconomic status (SES) differences. Previous studies investigating this association have used aggregate SES indicators from census tract of residence; we used census block-group data, representing a smaller, potentially more homogenous group. Methods: We included all African-American and Caucasian invasive cancers of the colon and rectum, lung and bronchus, female breast, cervix uteri, and prostate that were diagnosed between January 1, 1988 and December 31, 1992 in the Detroit area. Stage of disease at diagnosis was grouped as local or non-local. An SES value was calculated for each case using aggregate 1990 US Census data for education, poverty status, and occupation specific to each case's census block-group. Logistic regression analysis was used to model the probability of non-local stage using SES, race, age group, and sex as covariates. Results: SES was an independent predictor of stage at diagnosis for each cancer site, with cases from the highest SES block-group more likely to present with local stage disease than those from the lowest SES group. Race independently predicted stage only for breast and prostate cancers; African-Americans presented with more advanced stage than Caucasians. Conclusions: Based on census block-group aggregate data, SES is an important predictor of stage at diagnosis, most likely accounting for much of the disparity in stage between African-Americans and Caucasians for colorectal, lung, and cervical cancers. Biological factors may play a role in racial disparities for breast and prostate cancer stage at diagnosis.

Race, socioeconomic status and stage at diagnosis for five common malignancies

Background African-Americans have twice the risk of non-Hispanic whites for presenting with advanced-stage prostate cancer. To investigate the reasons for this difference, we evaluated the association between race/ethnicity and advanced-stage prostate cancer, adjusting for demographic, socioeconomic, clinical, and pathologic factors. Methods A population-based cohort of 3173 men diagnosed with prostate cancer between October 1, 1994, and October 31, 1995, was analyzed. Medical record abstracts and self-administered survey questionnaires were used to obtain information regarding race/ethnicity, age, marital status, insurance status, educational level, household income, employment status, comorbidity, urinary function, prostate-specific antigen level, tumor grade, and clinical stage. The odds ratio (OR) for advanced-stage prostate cancer was estimated with weighted logistic regression analysis. All P: values were two-sided. Results Clinically advanced-stage prostate cancers were detected more frequently in African-Americans (12.3%) and Hispanics (10.5%) than in non-Hispanic whites (6.3%). Socioeconomic, clinical, and pathologic factors each accounted for about 15% of the increased relative risk. After adjusting for all covariates, the risk remained statistically significantly increased for African-Americans (OR = 2.26; 95% confidence interval [CI] = 1.43 to 3.58) but not for Hispanics (OR = 1.23; 95% CI = 0.73 to 2.08). Conclusion Traditional socioeconomic, clinical, and pathologic factors accounted for the increased relative risk for presenting with advanced-stage prostate cancer in Hispanic but not in African-American men.

/pdf/racial-and-ethnic-differences-in-advanced-stage-prostate-4qsntrgz0z.pdf

W. Curtis Hunt

Papers

Racial and Ethnic Differences in Advanced-Stage Prostate Cancer: the Prostate Cancer Outcomes Study

Acute changes in cortical excitability in the cortex contralateral to focal intracerebral hemorrhage in the swine.