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      Age and Racial Differences among PSA-Detected (AJCC Stage T1cN0M0) Prostate Cancer in the U.S.: A Population-Based Study of 70,345 Men

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          Abstract

          Purpose: Few studies have evaluated the risk profile of prostate-specific antigen (PSA)-detected T1cN0M0 prostate cancer, defined as tumors diagnosed by needle biopsy because of elevated PSA levels without other clinical signs of disease. However, some men with stage T1cN0M0 prostate cancer may have high-risk disease (HRD), thus experiencing inferior outcomes as predicted by a risk group stratification model.

          Methods: We identified men diagnosed with stage T1cN0M0 prostate cancer from 2004 to 2008 reported to the surveillance, epidemiology, and end results (SEER) program. Multivariate logistic regression was used to model the probability of intermediate-risk-disease (IRD) (PSA ≥ 10 ng/ml but <20 ng/ml and/or GS 7), and high-risk-disease (HDR) (PSA ≥ 20 ng/ml, and/or GS ≥ 8), relative to low-risk disease (LRD) (PSA < 10 ng/ml and GS ≤ 6), adjusting for age, race, marital status, median household income, and area of residence.

          Results: A total of 70,345 men with PSA-detected T1cN0M0 prostate cancer were identified. Of these, 47.6, 35.9, and 16.5% presented with low-, intermediate-, and high-risk disease, respectively. At baseline (50 years of age), risk was higher for black men than for whites for HRD (OR 3.31, 95% CI 2.85–3.84). The ORs for age (per year) for HRD relative to LRD were 1.09 (95% CI 1.09–1.10) for white men, and as 1.06 (95% CI 1.05–1.07) for black men. Further, among a subgroup of men with low PSA (<10 ng/ml) T1cN0M0 prostate cancer, risk was also higher for black man than for white men at baseline (50 years of age) (OR 2.70, 95% CI 2.09–3.48). The ORs for age (per year) for HRD relative to LRD were 1.09 (95% CI 1.09–1.10) for white men, and as 1.06 (95% CI 1.05–1.07) for black men.

          Conclusion: A substantial proportion of men with PSA-detected prostate cancer as reported to the SEER program had HRD. Black race and older age were associated with a greater likelihood of HRD.

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          Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24.

          Julius Gudmundsson, Patrick Sulem, Andrei Manolescu … (2007)
          Prostate cancer is the most prevalent noncutaneous cancer in males in developed regions, with African American men having among the highest worldwide incidence and mortality rates. Here we report a second genetic variant in the 8q24 region that, in conjunction with another variant we recently discovered, accounts for about 11%-13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans. We made the current discovery through a genome-wide association scan of 1,453 affected Icelandic individuals and 3,064 controls using the Illumina HumanHap300 BeadChip followed by four replication studies. A key step in the discovery was the construction of a 14-SNP haplotype that efficiently tags a relatively uncommon (2%-4%) susceptibility variant in individuals of European descent that happens to be very common (approximately 42%) in African Americans. The newly identified variant shows a stronger association with affected individuals who have an earlier age at diagnosis.
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            Radical prostatectomy versus watchful waiting in early prostate cancer.

            Anna Bill-Axelson, Lars Holmberg, Mirja Ruutu … (2011)
            In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now report estimated 15-year results. From October 1989 through February 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy. Follow-up was complete through December 2009, with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death. Relative risks, with 95% confidence intervals, were estimated with the use of a Cox proportional-hazards model. During a median of 12.8 years, 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died (P=0.007). In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting, death was due to prostate cancer. This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6% and 20.7%, respectively (a difference of 6.1 percentage points; 95% confidence interval [CI], 0.2 to 12.0), and a relative risk with surgery of 0.62 (95% CI, 0.44 to 0.87; P=0.01). The survival benefit was similar before and after 9 years of follow-up, was observed also among men with low-risk prostate cancer, and was confined to men younger than 65 years of age. The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age. Among men who underwent radical prostatectomy, those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth (relative risk, 6.9; 95% CI, 2.6 to 18.4). Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer. Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment. (Funded by the Swedish Cancer Society and the National Institutes of Health.).
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              A common variant associated with prostate cancer in European and African populations.

              Laufey T. Amundadottir, Patrick Sulem, Julius Gudmundsson … (2006)
              With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 x 10(-11)). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of approximately 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry.
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Oncol
                Journal ID (iso-abbrev): Front Oncol
                Journal ID (publisher-id): Front. Oncol.
                Title: Frontiers in Oncology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 2234-943X
                Publication date (Electronic): 23 December 2013
                Publication date Collection: 2013
                Volume: 3
                Electronic Location Identifier: 312
                Affiliations
                [1] 1Department of Radiation Oncology, University of Rochester Medical Center , Rochester, NY, USA
                [2] 2Department of Urology, University of Rochester Medical Center , Rochester, NY, USA
                [3] 3Department of Biostatistics and Computational Biology, University of Rochester Medical Center , Rochester, NY, USA
                Author notes

                Edited by: Susan F. Slovin, Memorial Sloan-Kettering Cancer Center, USA

                Reviewed by: Min-Han Tan, Institute of Bioengineering and Nanotechnology, Singapore; Thomas L. Jang, Cancer Institute of New Jersey, USA

                *Correspondence: Hong Zhang, Department of Radiation Oncology, University of Rochester Medical Center, 601 Elmwood Avenue Box 647, Rochester, NY 14642, USA e-mail: hong_zhang@ 123456urmc.rochester.edu

                This article was submitted to Genitourinary Oncology, a section of the journal Frontiers in Oncology.

                Article
                DOI: 10.3389/fonc.2013.00312
                PMC ID: 3870291
                SO-VID: 25b8daac-1115-4552-a0c4-8d86a6adee98
                Copyright © Copyright © 2013 Zhang, Messing, Travis, Hyrien, Chen, Milano and Chen.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 18 September 2013
                Date accepted : 09 December 2013
                Page count
                Figures: 2, Tables: 6, Equations: 0, References: 48, Pages: 10, Words: 6897
                Categories
                Subject: Oncology
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: race,population-study,prostate cancer,age,seer,screen-detected
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: race, population-study, prostate cancer, age, seer, screen-detected

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