| 1. |
- Bonn, Stephanie E., et al.
(författare)
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Body mass index and weight change in men with prostate cancer : progression and mortality
- 2014
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Ingår i: Cancer Causes and Control. - : Springer Netherlands. - 0957-5243 .- 1573-7225. ; 25:8, s. 933-943
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Tidskriftsartikel (refereegranskat)abstract
- Body mass index (BMI) is a modifiable lifestyle factor that has been associated with an increased risk of fatal prostate cancer and biochemical recurrence. The main purpose of the present study was to investigate the association between the exposure BMI at the time of a prostate cancer diagnosis and weight change after diagnosis, and the outcomes of prostate cancer progression and mortality in a large cohort study. Data from 4,376 men diagnosed with clinically localized prostate cancer between 1997 and 2002 were analyzed. BMI and weight change were self-reported in 2007. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were estimated in complete-case analysis (n = 3,214) using Cox proportional hazards models. Progression was experienced among 639 (14.6 %) of the study participants, and in total, 450 (10.3 %) deaths of any cause and 134 (3.1 %) prostate cancer-specific deaths were recorded during follow-up. Obese men had a 47 % increased rate of overall mortality compared to normal weight men (HR 1.47, 95 % CI 1.03-2.10). No statistically significant associations were found for BMI and prostate cancer progression or prostate cancer-specific mortality. A weight loss > 5 % after diagnosis almost doubled the rate of overall mortality compared to maintaining a stable weight (HR 1.94, 95 % CI 1.41-2.66), while a weight gain > 5 % was associated with an almost doubled increased rate of prostate cancer-specific mortality (HR 1.93, 95 % CI 1.18-3.16). Being obese was associated with an increased rate of overall mortality, and gaining weight after a prostate cancer diagnosis was associated with an increased rate of prostate cancer-specific mortality.
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| 2. |
- Christensen, G Bryce, et al.
(författare)
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Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses.
- 2010
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 70, s. 735-744
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS: We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS: Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11-q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9 cM. CONCLUSIONS: Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate (c) 2010 Wiley-Liss, Inc.
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| 3. |
- Jin, Guangfu, et al.
(författare)
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Validation of prostate cancer risk-related loci identified from genome-wide association studies using family-based association analysis : evidence from the International Consortium for Prostate Cancer Genetics (ICPCG)
- 2012
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:7, s. 1095-1103
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Tidskriftsartikel (refereegranskat)abstract
- Multiple prostate cancer (PCa) risk-related loci have been discovered by genome-wide association studies (GWAS) based on case-control designs. However, GWAS findings may be confounded by population stratification if cases and controls are inadvertently drawn from different genetic backgrounds. In addition, since these loci were identified in cases with predominantly sporadic disease, little is known about their relationships with hereditary prostate cancer (HPC). The association between seventeen reported PCa susceptibility loci was evaluated with a family-based association test using 1,979 hereditary PCa families of European descent collected by members of the International Consortium for Prostate Cancer Genetics, with a total of 5,730 affected men. The risk alleles for 8 of the 17 loci were significantly over-transmitted from parents to affected offspring, including SNPs residing in 8q24 (regions 1, 2 and 3), 10q11, 11q13, 17q12 (region 1), 17q24 and Xp11. In subgroup analyses, three loci, at 8q24 (regions 1 and 2) plus 17q12, were significantly over-transmitted in hereditary PCa families with five or more affected members, while loci at 3p12, 8q24 (region 2), 11q13, 17q12 (region 1), 17q24 and Xp11 were significantly over-transmitted in HPC families with an average age of diagnosis at 65 years or less. Our results indicate that at least a subset of PCa risk-related loci identified by case-control GWAS are also associated with disease risk in HPC families.
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| 4. |
- Karlsson Thellenberg, Camilla, et al.
(författare)
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Risk of prostate cancer after trans urethral resection of BPH : a cohort and nested case-control study
- 2011
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 3:4, s. 4127-4138
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological and experimental evidence suggests that inflammation plays a role in both prostate cancer (PCa) and benign prostate hyperplasia (BPH). This study evaluates the risk of PC after transurethral resection (TURP) for BPH and estimates the PCa risk related to presence of inflammation in the resected material. The Pathology Department at the University Hospital of Umea (Umea, Sweden) identified BPH cases (n = 7,901) that underwent TURP between 1982 and 1997. Using these pathological specimens, we compared the incidence of PCa in the cohort to the population and calculated the standardized incidence and mortality ratios (SIR and SMR). Inflammation, the androgen receptor (AR), and p53 were evaluated in a nested case-control study of 201 cases and controls. Inflammation was graded severe or mild-moderate. In the follow-up period after TURP, cases developed prostate cancer and the controls did not. After TURP, SIR for prostate cancer increased [1.26, CI 95% (1.17–1.35)], whereas SMR decreased [0.59, CI 95% (0.47–0.73)]. Presence of inflammation at the time of TURP did not differ between cases and controls nor were there differences in p53 or AR staining. The data suggest a small increased risk of PCa after TURP and decreased PCa mortality. Inflammation at the time of TURP is not associated with PCa risk in this material. The increased PCa risk may be attributed to increased surveillance and PSA screening.
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| 5. |
- Klein, Robert J, et al.
(författare)
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Blood biomarker levels to aid discovery of cancer-related single-nucleotide polymorphisms : kallikreins and prostate cancer
- 2010
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Ingår i: Cancer Prevention Research. - : American Association for Cancer Research. - 1940-6207 .- 1940-6215. ; 3:5, s. 611-619
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms associated with prostate cancer include those in three genes encoding major secretory products of the prostate: KLK2 (encoding kallikrein-related peptidase 2; hK2), KLK3 (encoding prostate-specific antigen; PSA), and MSMB (encoding beta-microseminoprotein). PSA and hK2, members of the kallikrein family, are elevated in sera of men with prostate cancer. In a comprehensive analysis that included sequencing of all coding, flanking, and 2 kb of putative promoter regions of all 15 kallikrein (KLK) genes spanning approximately 280 kb on chromosome 19q, we identified novel single-nucleotide polymorphisms (SNP) and genotyped 104 SNPs in 1,419 cancer cases and 736 controls in Cancer Prostate in Sweden 1, with independent replication in 1,267 cases and 901 controls in Cancer Prostate in Sweden 2. This verified prior associations of SNPs in KLK2 and in MSMB (but not in KLK3) with prostate cancer. Twelve SNPs in KLK2 and KLK3 were associated with levels of PSA forms or hK2 in plasma of control subjects. Based on our comprehensive approach, this is likely to represent all common KLK variants associated with these phenotypes. A T allele at rs198977 in KLK2 was associated with increased cancer risk and a striking decrease of hK2 levels in blood. We also found a strong interaction between rs198977 genotype and hK2 levels in blood in predicting cancer risk. Based on this strong association, we developed a model for predicting prostate cancer risk from standard biomarkers, rs198977 genotype, and rs198977 x hK2 interaction; this model had greater accuracy than did biomarkers alone (area under the receiver operating characteristic curve, 0.874 versus 0.866), providing proof in principle to clinical application for our findings.
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| 6. |
- Lin, Daniel W., et al.
(författare)
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Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality
- 2011
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Philadelphia : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 20:9, s. 1928-1936
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prostate cancer is the second leading cause of cancer-related deaths in men, accounting for more than 30,000 deaths annually. The purpose of this study was to test whether variation in selected candidate genes in biological pathways of interest for prostate cancer progression could help distinguish patients at higher risk for fatal prostate cancer. Methods: In this hypothesis-driven study, we genotyped 937 single nucleotide polymorphisms (SNPs) in 156 candidate genes in a population-based cohort of 1,309 prostate cancer patients. We identified 22 top-ranking SNPs (P <= 0.01, FDR <= 0.70) associated with prostate cancer-specific mortality (PCSM). A subsequent validation study was completed in an independent population-based cohort of 2,875 prostate cancer patients. Results: Five SNPs were validated (P <= 0.05) as being significantly associated with PCSM, one each in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes. Compared with patients with 0 to 2 of the at-risk genotypes those with 4 to 5 at-risk genotypes had a 50% (95% CI, 1.2-1.9) higher risk of PCSM and risk increased with the number of at-risk genotypes carried (P(trend) = 0.001), adjusting for clinicopathologic factors known to influence prognosis. Conclusion: Five genetic markers were validated to be associated with lethal prostate cancer. Impact: This is the first population-based study to show that germline genetic variants provide prognostic information for prostate cancer-specific survival. The clinical utility of this five-SNP panel to stratify patients at higher risk for adverse outcomes should be evaluated. Cancer Epidemiol Biomarkers Prev; 20(9); 1928-36. (C)2011 AACR.
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| 7. |
- Lindström, Sara, et al.
(författare)
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Sequence variants in the TLR4 and TLR6-1-10 genes and prostate cancer risk. Results based on pooled analysis from three independent studies.
- 2010
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 19:3, s. 873-876
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetic variation in two members of the Toll-like receptor family, TLR4 and the gene cluster TLR6-1-10, has been implicated in prostate cancer in several studies but the associated alleles have not been consistent across reports. METHODS: We did a pooled analysis combining genotype data from three case-control studies, Cancer of the Prostate in Sweden, the Health Professionals Follow-up Study, and the Prostate, Lung, Colon and Ovarian Cancer Screening Trial, with data from 3,101 prostate cancer cases and 2,523 controls. We did imputation to obtain dense coverage of the genes and comparable genotype data for all cohorts. In total, 58 single nucleotide polymorphisms in TLR4 and 96 single nucleotide polymorphisms in TLR6-1-10 were genotyped or imputed and analyzed in the entire data set. We did a cohort-specific analysis as well as meta-analysis and pooled analysis. We also evaluated whether the analyses differed by age or disease severity. RESULTS: We observed no overall association between genetic variation at the TLR4 and TLR6-1-10 loci and risk of prostate cancer. CONCLUSIONS: Common germ line genetic variation in TLR4 and TLR6-1-10 did not seem to have a strong association with risk of prostate cancer. IMPACT: This study suggests that earlier associations between prostate cancer risk and TLR4 and TLR6-1-10 sequence variants were chance findings. To definitely assess the causal relationship between TLR sequence variants and prostate cancer risk, very large sample sizes are needed.
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| 8. |
- Szulkin, Robert, et al.
(författare)
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Prostate cancer risk variants are not associated with disease progression
- 2012
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 72:1, s. 30-39
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Currently used prognostic markers are limited in their ability to accurately predict disease progression among patients with localized prostate cancer. We examined 23 reported prostate cancer susceptibility variants for association with disease progression. METHODS: Disease progression was explored among 4,673 Swedish patients treated for clinically localized prostate cancer between 1997 and 2002. Prostate cancer progression was defined according to primary treatment as a composed event reflecting termination of deferred treatment, biochemical recurrence, local progression, or presence of distant metastasis. Association between single variants, and all variants combined, were performed in Cox regression analysis assuming both log-additive and co-dominant genetic models. RESULTS: Three of the 23 genetic variants explored were nominally associated with prostate cancer progression; rs9364554 (P = 0.041) on chromosome 6q25 and rs10896449 (P = 0.029) on chromosome 11q13 among patients treated with curative intent; and rs4054823 (P = 0.008) on chromosome 17p12 among patients on surveillance. However, none of these associations remained statistically significant after correction for multiple testing. The combined effect of all susceptibility variants was not associated with prostate cancer progression neither among patients receiving treatment with curative intent (P = 0.14) nor among patients on surveillance (P = 0.92). CONCLUSIONS: We observed no evidence for an association between any of 23 established prostate cancer genetic risk variants and disease progression. Accumulating evidence suggests separate genetic components for initiation and progression of prostate cancer. Future studies systematically searching for genetic risk variants associated with prostate cancer progression and prognosis are warranted. Prostate © 2011 Wiley-Liss, Inc.
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| 9. |
- Teerlink, Craig C., et al.
(författare)
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Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate cancer associated SNPs for familial disease
- 2014
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Ingår i: Human Genetics. - : Springer. - 0340-6717 .- 1432-1203. ; 133:3, s. 347-356
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Tidskriftsartikel (refereegranskat)abstract
- Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p a parts per thousand currency sign 1E (-3)) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may contribute risk to aggressive disease.
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| 10. |
- Wiinikka, Henrik, et al.
(författare)
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Emissions of heavy metals during fixed-bed combustion of six biomass fuels
- 2013
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Ingår i: Energy & Fuels. - : American Chemical Society (ACS). - 0887-0624 .- 1520-5029. ; 27:2, s. 1073-1080
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Tidskriftsartikel (refereegranskat)abstract
- Few studies examine heavy metal emissions during the small-scale combustion of various solid biofuels. This issue may become more important, as one can expect new regulations governing such emissions from biomass combustion similar to those governing waste incineration. This paper investigates the emissions of particulate-associated heavy metals (i.e., Sb, As, Cd, Co, Cr, Cu, Pb, Mn, Ni, Tl, V, Hg, and Zn) during the fixed-bed combustion of six solid biofuels (i.e., stemwood from birch and pine/spruce, bark from birch and pine, salix, and oat grains) and of peat and bituminous coal for comparison. The results indicate that the flue gas concentration (normalized to 11% O2) of the sum of all measured metals (Zn excluded) during the biomass combustion tests ranged from 57 μg Nm-3 for birch stemwood to 198 μg Nm-3 for birch bark. The concentration of Zn in the flue gas was generally considerably higher than those of the other metals, ranging from 646 μg Nm-3 for spruce/pine stemwood to 7948 μg Nm-3 for birch bark. Compared with coal and peat, the biomass fuels produced higher Zn emissions, but lower or similar emissions of the sum of the other metals. The volatile behavior and concentration of the metal in the flue gases as a function of the heavy metal in the fuel are also presented for selected heavy metals.
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