| 1. |
- Amundadottir, Laufey T., et al.
(author)
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A common variant associated with prostate cancer in European and African populations
- 2006
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In: Nature Genetics. - DeCODE Genet, IS-101 Reykjavik, Iceland. Univ Iceland, Landspitali Hosp, Dept Pathol, IS-101 Reykjavik, Iceland. Univ Iceland, Landspitali Hosp, Dept Urol, IS-101 Reykjavik, Iceland. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Orebro Univ Hosp, Dept Urol & Clin Med, Orebro, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 38:6, s. 652-658
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Journal article (peer-reviewed)abstract
- 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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| 2. |
- Hedelin, Maria, et al.
(author)
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Dietary intake of phytoestrogens, estrogen receptor-beta polymorphisms and the risk of prostate cancer
- 2006
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In: The Prostate. - Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. Orebro Univ Hosp, Dept Urol, Orebro, Sweden. Ctr Assessment Med Technol, Orebro, Sweden. Umea Univ, Dept Radiat Sci Oncol, Umea, Sweden. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. : Wiley-Liss. - 0270-4137 .- 1097-0045. ; 66:14, s. 1512-1520
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Journal article (peer-reviewed)abstract
- BACKGROUND: The causes of prostate cancer are poorly understood, but genetic factors may be more important than for many other malignancies, and dietary phytoestrogens may be protective. Because phytoestrogens bind tightly to the estrogen receptor-beta, we conducted an epidemiologic investigation of synergistic effects between phytoestrogen intake and estrogen receptor-beta gene polymorphisms. METHODS: We performed a population-based case-control study in Sweden. All participants reported their phytoestrogen intake and donated a blood sample. We identified four haplotype-tagging single nucleotide polymorphisms (htSNPs) and genotyped these htSNPs in 1314 prostate cancer patients and 782 controls. Odds ratios were estimated by multivariate logistic regression. Interactions between phytoestrogen intake and estrogen receptor-beta SNPs on prostate cancer risk were evaluated considering both multiplicative and additive effect scales. RESULTS: We found a significant multiplicative interaction (P = 0.04) between dietary intake of phytoestrogens and a promoter SNP in the estrogen receptor-beta gene (rs 2987983-13950), but not with any of the three other htSNPs (P = 0.11, 0.69, 0.85). Among carriers of the variant promoter alleles, we found strong inverse associations with increasing intake of total phytoestrogens (odds ratio for highest vs. lowest quartile = 0.43; P for trend <0.001), isoflavonoids (odds ratio = 0.63; P for trend = 0.05), and coumestrol (odds ratio = 0.57; P for trend = 0.003). We found no association between phytoestrogens and prostate cancer among carriers homozygous for the wild-type allele (TT). CONCLUSIONS: Our study provides strong evidence that high intake of phytoestrogens substantially reduce prostate cancer risk among men with specific polymorphic variation in the promoter region of the estrogen receptor-beta gene.
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| 3. |
- Rider, Jennifer R., et al.
(author)
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Long-term Outcomes Among Noncuratively Treated Men According to Prostate Cancer Risk Category in a Nationwide, Population-based Study
- 2013
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In: European Urology. - Amsterdam, Netherlands : Elsevier BV. - 0302-2838 .- 1873-7560. ; 63:1, s. 88-96
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Journal article (peer-reviewed)abstract
- Background: Limited data exist on long-term outcomes among men with prostate cancer (PCa) from population-based cohorts incorporating information on clinical risk category. Objective: To assess 15-yr mortality for men with PCa treated with noncurative intent according to clinical stage, Gleason score (GS), serum levels of prostate specific antigen (PSA), comorbidity, and age. Design, setting, and participants: Register-based cohort study of 76 437 cases in the National Prostate Cancer Register (NPCR) of Sweden diagnosed from 1991 through 2009 and treated with noncurative intent. Each case was placed in one of five risk categories: (1) low risk: T1-T2 tumor, PSA level <10 ng/ml, and GS <= 6; (2) intermediate risk: T1-T2 tumor and PSA level 10-<20 ng/ml or GS 7; (3) high risk: T3 tumor or PSA level 20-<50 ng/ml or GS >= 8; (4) regional metastases: N1 or T4 tumor or PSA level 50-100 ng/ml; and (5) distant metastases: M1 tumor or PSA >= 100 ng/ml. Outcome measurements and statistical analysis: Ten-and 15-yr cumulative risk of death after diagnosis from PCa, cardiovascular disease, and other causes. Results and limitations: Among men with a Charlson Comorbidity Index (CCI) score of 0, no differences were found in observed versus expected all-cause mortality in the low-risk group. Observed mortality was only slightly greater in the intermediate-risk group, but men with high-risk localized PCa or more advanced disease had substantially higher mortality than expected. CCI was strongly associated with cumulative 10-yr mortality from causes other than PCa, especially for men <65 yr. Limitations include potential misclassification in risk category due to GS assignment. Conclusions: PCa mortality rates vary 10-fold according to risk category. The risk of death from causes other than PCa is most strongly related to comorbidity status in younger men. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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| 4. |
- Sun, Jielin, et al.
(author)
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Evidence for two independent prostate cancer risk-associated loci in the HNF1B gene at 17q12
- 2008
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In: Nature Genetics. - London : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 40:10, s. 1153-1155
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Journal article (other academic/artistic)abstract
- We carried out a fine-mapping study in the HNF1B gene at 17q12 in two study populations and identified a second locus associated with prostate cancer risk, 26 kb centromeric to the first known locus (rs4430796); these loci are separated by a recombination hot spot. We confirmed the association with a SNP in the second locus (rs11649743) in five additional populations, with P = 1.7 10-9 for an allelic test of the seven studies combined. The association at each SNP remained significant after adjustment for the other SNP.
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| 5. |
- Wiklund, Fredrik, et al.
(author)
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Lifetime total physical activity and prostate cancer risk : a population-based case-control study in Sweden
- 2008
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In: European Journal of Epidemiology. - Berlin : Springer. - 0393-2990 .- 1573-7284. ; 23:11, s. 739-746
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Journal article (peer-reviewed)abstract
- The etiologic role of physical activity in prostate cancer development is unclear. We assessed the association between lifetime total physical activity and prostate cancer risk in a Swedish population-based case–control study comprising 1,449 incident prostate cancer cases and 1,118 unaffected population controls. Information regarding physical activity was obtained via a self-administered questionnaire assessing occupational, household, and recreational activity separately at various ages throughout an individual’s lifetime. Clinical data (TNM-classification, Gleason sum and PSA) was obtained from linkage to the National Prostate Cancer Registry. Overall, we observed no association between lifetime total physical activity and prostate cancer risk (odds ratio [OR] = 1.04, 95% confidence interval [CI] = 0.77–1.41 for ≥49.7 vs. <41.9 metabolic equivalent-hours per day). There was a significantly increased risk of prostate cancer in the most active men compared with the least active men in household (OR = 1.44, 95% CI = 1.08–1.92) and recreational physical activity (OR = 1.56, 95% CI = 1.16–2.10). Comparing the most active with the least active men, total physical activity was not associated with either localized disease (OR = 0.95, 95% CI = 0.67–1.34) or advanced disease (OR = 1.19, 95% CI = 0.83–1.71). These findings do not support the hypothesis that physical activity uniformly protects against prostate cancer development.
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| 6. |
- Wiklund, Fredrik, et al.
(author)
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Risk of bilateral renal cell cancer
- 2009
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In: Journal of Clinical Oncology. - Alexandria, USA : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 27:23, s. 3737-41
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Journal article (peer-reviewed)abstract
- Purpose: The risk of developing bilateral kidney cancer has not been adequately defined in any large, population-based study with long-term follow-up to our knowledge.Patients and methods: We estimated the risk of metachronous bilateral renal cell cancer in patients diagnosed with unilateral kidney cancer, as recorded in the nationwide cancer registries of Norway and Sweden. Altogether 28,642 patients were followed for an average of 4.4 years. The standardized incidence ratio--the ratio of the observed number of bilateral cancers to the number expected on the basis of the incidence in the Norwegian and Swedish population at large--was used as a measure of relative risk. We used multivariate Poisson regression to separate the effects of the explanatory variables.Results: A synchronous bilateral renal cell cancer was reported in 86 patients. A total of 112 metachronous bilateral cancers were recorded during 126,493 person-years of follow-up compared with 35.8 expected, yielding an overall relative risk (RR) of 3.1 (95% CI, 2.6 to 3.8) and a cumulative incidence of 0.8% after 20 or more years of follow-up. In the multivariate analyses, risk increased monotonically with younger age at first diagnosis (P for trend < .001); compared with patients who were 60 years or older, those younger than 40 years were at a 17-fold higher risk (RR = 17.4; 95% CI, 10.1 to 29.8). We also found a modest but statistically significant decreasing trend with increasing duration of follow-up.Conclusion: The risk of metachronous bilateral renal cell cancer is drastically higher among patients first affected at a young age, suggesting a subset of early onset renal cell cancer with a strong genetic component.
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| 7. |
- Xu, Jianfeng, et al.
(author)
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Estimation of absolute risk for prostate cancer using genetic markers and family history
- 2009
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In: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 69:14, s. 1565-1572
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Journal article (peer-reviewed)abstract
- BACKGROUND: Multiple DNA sequence variants in the form of single-nucleotide polymorphisms (SNPs) have been found to be reproducibly associated with prostate cancer (PCa) risk. METHODS: Absolute risk for PCa among men with various numbers of inherited risk alleles and family history of PCa was estimated in a population-based case-control study in Sweden (2,893 cases and 1,781 controls), and a nested case-control study from the Prostate, Lung, Colon and Ovarian (PLCO) Cancer Screening Trial in the U.S. (1,172 cases and 1,157 controls). RESULTS: Increased number of risk alleles and positive family history were independently associated with PCa risk. Considering men with 11 risk alleles (mode) and negative family history as having baseline risk, men who had >or=14 risk alleles and positive family history had an odds ratio (OR) of 4.92 [95% confidence interval (CI): 3.64-6.64] in the Swedish study. These associations were confirmed in the U.S. population. Once a man's SNP genotypes and family history are known, his absolute risk for PCa can be readily calculated and easily interpreted. For example, 55-year-old men with a family history and >or=14 risk alleles have a 52% and 41% risk of being diagnosed with PCa in the next 20 years in the Swedish and U.S. populations, respectively. In comparison, without knowledge of genotype and family history, these men had an average population absolute risk of 13%. CONCLUSION: This risk prediction model may be used to identify men at considerably elevated PCa risk who may be selected for chemoprevention.
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| 8. |
- Zheng, S. Lilly, et al.
(author)
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Genetic variants and family history predict prostate cancer similar to prostate-specific antigen
- 2009
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In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 15:3, s. 1105-1111
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Journal article (peer-reviewed)abstract
- PURPOSE: Although prostate-specific antigen (PSA) is the best biomarker for predicting prostate cancer, its predictive performance needs to be improved. Results from the Prostate Cancer Prevention Trial revealed the overall performance measured by the areas under curve of the receiver operating characteristic at 0.68. The goal of the present study is to assess the ability of genetic variants as a PSA-independent method to predict prostate cancer risk. EXPERIMENTAL DESIGN: We systematically evaluated all prostate cancer risk variants that were identified from genome-wide association studies during the past year in a large population-based prostate cancer case-control study population in Sweden, including 2,893 prostate cancer patients and 1,781 men without prostate cancer. RESULTS: Twelve single nucleotide polymorphisms were independently associated with prostate cancer risk in this Swedish study population. Using a cutoff of any 11 risk alleles or family history, the sensitivity and specificity for predicting prostate cancer were 0.25 and 0.86, respectively. The overall predictive performance of prostate cancer using genetic variants, family history, and age, measured by areas under curve was 0.65 (95% confidence interval, 0.63-0.66), significantly improved over that of family history and age (0.61%; 95% confidence interval, 0.59-0.62; P = 2.3 x 10(-10)). CONCLUSION: The predictive performance for prostate cancer using genetic variants and family history is similar to that of PSA. The utility of genetic testing, alone and in combination with PSA levels, should be evaluated in large studies such as the European Randomized Study for Prostate Cancer trial and Prostate Cancer Prevention Trial.
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| 9. |
- Zheng, S. Lilly, et al.
(author)
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Two independent prostate cancer risk-associated Loci at 11q13
- 2009
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In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 18:6, s. 1815-1820
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Journal article (peer-reviewed)abstract
- Single nucleotide polymorphisms (SNP) at 11q13 were recently implicated in prostate cancer risk by two genome-wide association studies and were consistently replicated in multiple study populations. To explore prostate cancer association in the regions flanking these SNPs, we genotyped 31 tagging SNPs in a approximately 110 kb region at 11q13 in a Swedish case-control study (Cancer of the Prostate in Sweden), including 2,899 cases and 1,722 controls. We found evidence of prostate cancer association for the previously implicated SNPs including rs10896449, which we termed locus 1. In addition, multiple SNPs on the centromeric side of the region, including rs12418451, were also significantly associated with prostate cancer risk (termed locus 2). The two groups of SNPs were separated by a recombination hotspot. We then evaluated these two representative SNPs in an additional approximately 4,000 cases and approximately 3,000 controls from three study populations and confirmed both loci at 11q13. In the combined allelic test of all four populations, P = 4.0 x 10(-11) for rs10896449 at locus 1 and P = 1.2 x 10(-6) for rs12418451 at locus 2, and both remained significant after adjusting for the other locus and study population. The prostate cancer association at these two 11q13 loci was unlikely confounded by prostate-specific antigen (PSA) detection bias because neither SNP was associated with PSA levels in controls. Unlike locus 1, in which no known gene is located, several putative mRNAs are in close proximity to locus 2. Additional confirmation studies at locus 2 and functional studies for both loci are needed to advance our knowledge on the etiology of prostate cancer.
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