| 61. |
- Shui, Irene M, et al.
(författare)
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Genetic variation in the toll-like receptor 4 and prostate cancer incidence and mortality
- 2012
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Ingår i: The Prostate. - : Wiley-Blackwell. - 0270-4137 .- 1097-0045. ; 72:2, s. 209-216
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Common genetic variants in the Toll-like receptor 4 (TLR4), which is involved in inflammation and immune response pathways, may be important for prostate cancer.METHODS: In a large nested case-control study of prostate cancer in the Physicians' Health Study (1982-2004), 10 single nucleotide polymorphisms (SNPs) were selected and genotyped to capture common variation within the TLR4 gene as well as 5 kb up and downstream. Unconditional logistic regression was used to assess associations of these SNPs with total prostate cancer incidence, and with prostate cancers defined as advanced stage/lethal (T3/T4, M1/N1(T1-T4), lethal) or high Gleason grade (7 (4 + 3) or greater). Cox-proportional hazards regression was used to assess progression to metastases and death among prostate cancer cases.RESULTS: The study included 1,267 controls and 1,286 incident prostate cancer cases, including 248 advanced stage/lethal and 306 high grade cases. During a median follow-up of 10.6 years, 183 men died of prostate cancer or developed distant metastases. No statistically significant associations between the TLR4 SNPs were found for total prostate cancer incidence, including SNPs for which an association was reported in other published studies. Additionally, there were no significant associations with TLR4 SNPS and the incidence of advanced stage/lethal, or high grade cancers; nor was there evidence among prostate cancer cases for associations of TLR4 SNPs with progression to prostate cancer specific mortality or bony metastases.CONCLUSIONS: Results from this prospective nested case-control study suggest that genetic variation across TLR4 alone is not strongly associated with prostate cancer risk or mortality.
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| 62. |
- Shui, Irene M., et al.
(författare)
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Prostate Cancer (PCa) Risk Variants and Risk of Fatal PCa in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium
- 2014
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 65:6, s. 1069-1075
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Tidskriftsartikel (refereegranskat)abstract
- Background: Screening and diagnosis of prostate cancer (PCa) is hampered by an inability to predict who has the potential to develop fatal disease and who has indolent cancer. Studies have identified multiple genetic risk loci for PCa incidence, but it is unknown whether they could be used as biomarkers for PCa-specific mortality (PCSM). Objective: To examine the association of 47 established PCa risk single-nucleotide polymorphisms (SNPs) with PCSM. Design, setting, and participants: We included 10 487 men who had PCa and 11 024 controls, with a median follow-up of 8.3 yr, during which 1053 PCa deaths occurred. Outcome measurements and statistical analysis: The main outcome was PCSM. The risk allele was defined as the allele associated with an increased risk for PCa in the literature. We used Cox proportional hazards regression to calculate the hazard ratios of each SNP with time to progression to PCSM after diagnosis. We also used logistic regression to calculate odds ratios for each risk SNP, comparing fatal PCa cases to controls. Results and limitations: Among the cases, we found that 8 of the 47 SNPs were significantly associated (p < 0.05) with time to PCSM. The risk allele of rs11672691 (intergenic) was associated with an increased risk for PCSM, while 7 SNPs had risk alleles inversely associated (rs13385191 [C2orf43], rs17021918 [PDLIM5], rs10486567 [JAZF1], rs6465657 [LMTK2], rs7127900 (intergenic), rs2735839 [KLK3], rs10993994 [MSMB], rs13385191 [C2orf43]). In the case-control analysis, 22 SNPs were associated (p < 0.05) with the risk of fatal PCa, but most did not differentiate between fatal and nonfatal PCa. Rs11672691 and rs10993994 were associated with both fatal and nonfatal PCa, while rs6465657, rs7127900, rs2735839, and rs13385191 were associated with nonfatal PCa only. Conclusions: Eight established risk loci were associated with progression to PCSM after diagnosis. Twenty-two SNPs were associated with fatal PCa incidence, but most did not differentiate between fatal and nonfatal PCa. The relatively small magnitudes of the associations do not translate well into risk prediction, but these findings merit further follow-up, because they may yield important clues about the complex biology of fatal PCa. Patient summary: In this report, we assessed whether established PCa risk variants could predict PCSM. We found eight risk variants associated with PCSM: One predicted an increased risk of PCSM, while seven were associated with decreased risk. Larger studies that focus on fatal PCa are needed to identify more markers that could aid prediction. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 63. |
- Thorgeirsson, Tryggvi, et al.
(författare)
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Intracellular location of BRCA2 protein expression and prostate cancer progression in the Swedish Watchful Waiting Cohort
- 2016
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Ingår i: Carcinogenesis. - Oxford, United Kingdom : Oxford University Press. - 0143-3334 .- 1460-2180. ; 37:3, s. 262-268
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer patients with inherited BRCA2 mutations have a survival disadvantage. However, it is unknown whether progression is associated with BRCA2 protein expression in diagnostic prostate cancer tissue, among men without inherited mutations. We conducted a nested case-control study within the Swedish Watchful Waiting cohort. The case group included all 71 patients who died from prostate cancer within 5 years from diagnosis and controls were all patients (n = 165) who lived at least 7 years after diagnosis. Tissue microarrays were stained using antibodies for C- and N-terminal domains of the BRCA2 protein. Location (nuclear, cytoplasmic and membranous) and magnitude (intensity and percentage) of expression were assessed. Logistic regression models produced odds ratios (OR) and 95% confidence intervals (CI) adjusted for age, year of diagnosis and Gleason score. Positive BRCA2 staining at the cell membrane was associated with reduced risk of death within 5 years (N-terminal: OR = 0.47, 95% CI = 0.21-1.04, P = 0.06; C-terminal: OR = 0.41, 95% CI = 0.18-0.91, P = 0.03) and low Gleason scores (P = 0.006). Positive cytoplasmic C-terminal staining was associated with higher Gleason scores and increased lethality (OR = 3.61, 95% CI = 1.61-8.07, P = 0.002). BRCA2 protein expression at the cell membrane and lack of C-terminal expression in the cytoplasm were associated with a reduced risk of rapidly fatal prostate cancer. BRCA2 protein expression in prostate cancer tissue may have independent prognostic value. The potential biological significance of BRCA2 expression at the cell membrane warrants further investigation.
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| 64. |
- Torfadottir, Johanna E, et al.
(författare)
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Milk intake in early life and risk of advanced prostate cancer
- 2012
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 175:2, s. 144-153
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Tidskriftsartikel (refereegranskat)abstract
- The authors investigated whether early-life residency in certain areas of Iceland marked by distinct differences in milk intake was associated with risk of prostate cancer in a population-based cohort of 8,894 men born between 1907 and 1935. Through linkage to cancer and mortality registers, the men were followed for prostate cancer diagnosis and mortality from study entry (in waves from 1967 to 1987) through 2009. In 2002-2006, a subgroup of 2,268 participants reported their milk intake in early, mid-, and current life. During a mean follow-up period of 24.3 years, 1,123 men were diagnosed with prostate cancer, including 371 with advanced disease (stage 3 or higher or prostate cancer death). Compared with early-life residency in the capital area, rural residency in the first 20 years of life was marginally associated with increased risk of advanced prostate cancer (hazard ratio = 1.29, 95% confidence interval (CI): 0.97, 1.73), particularly among men born before 1920 (hazard ratio = 1.64, 95% CI: 1.06, 2.56). Daily milk consumption in adolescence (vs. less than daily), but not in midlife or currently, was associated with a 3.2-fold risk of advanced prostate cancer (95% CI: 1.25, 8.28). These data suggest that frequent milk intake in adolescence increases risk of advanced prostate cancer.
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| 65. |
- Torfadottir, Johanna E., et al.
(författare)
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Rye bread consumption in early life and reduced risk of advanced prostate cancer
- 2012
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Ingår i: Cancer Causes and Control. - : Springer. - 0957-5243 .- 1573-7225. ; 23:6, s. 941-950
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether consumption of whole-grain rye bread, oatmeal, and whole-wheat bread, during different periods of life, is associated with risk of prostate cancer (PCa).METHODS: From 2002 to 2006, 2,268 men, aged 67-96 years, reported their dietary habits in the AGES-Reykjavik cohort study. Dietary habits were assessed for early life, midlife, and current life using a validated food frequency questionnaire. Through linkage to cancer and mortality registers, we retrieved information on PCa diagnosis and mortality through 2009. We used regression models to estimate odds ratios (ORs) and hazard ratios (HRs) for PCa according to whole-grain consumption, adjusted for possible confounding factors including fish, fish liver oil, meat, and milk intake.RESULTS: Of the 2,268 men, 347 had or were diagnosed with PCa during follow-up, 63 with advanced disease (stage 3+ or died of PCa). Daily rye bread consumption in adolescence (vs. less than daily) was associated with a decreased risk of PCa diagnosis (OR = 0.76, 95 % confidence interval (CI): 0.59-0.98) and of advanced PCa (OR = 0.47, 95 % CI: 0.27-0.84). High intake of oatmeal in adolescence (≥5 vs. ≤4 times/week) was not significantly associated with risk of PCa diagnosis (OR = 0.99, 95 % CI: 0.77-1.27) nor advanced PCa (OR = 0.67, 95 % CI: 0.37-1.20). Midlife and late life consumption of rye bread, oatmeal, or whole-wheat bread was not associated with PCa risk.CONCLUSION: Our results suggest that rye bread consumption in adolescence may be associated with reduced risk of PCa, particularly advanced disease.
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| 66. |
- Tyekucheva, Svitlana, et al.
(författare)
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Stromal and epithelial transcriptional map of initiation progression and metastatic potential of human prostate cancer
- 2017
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Ingår i: Nature Communications. - London, United Kingdom : Nature Publishing Group. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- While progression from normal prostatic epithelium to invasive cancer is driven by molecular alterations, tumor cells and cells in the cancer microenvironment are co-dependent and co-evolve. Few human studies to date have focused on stroma. Here, we performed gene expression profiling of laser capture microdissected normal non-neoplastic prostate epithelial tissue and compared it to non-transformed and neoplastic low-grade and high-grade prostate epithelial tissue from radical prostatectomies, each with its immediately surrounding stroma. Whereas benign epithelium in prostates with and without tumor were similar in gene expression space, stroma away from tumor was significantly different from that in prostates without cancer. A stromal gene signature reflecting bone remodeling and immune-related pathways was upregulated in high compared to low-Gleason grade cases. In validation data, the signature discriminated cases that developed metastasis from those that did not. These data suggest that the microenvironment may influence prostate cancer initiation, maintenance, and metastatic progression.Stromal cells contribute to tumor development but the mechanisms regulating this process are still unclear. Here the authors analyze gene expression profiles in the prostate and show that stromal gene signature changes ahead of the epithelial gene signature as prostate cancer initiates and progresses.
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| 67. |
- Ugge, Henrik, et al.
(författare)
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Circulating inflammation markers and prostate cancer
- 2019
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Ingår i: The Prostate. - : Alan R. Liss Inc.. - 0270-4137 .- 1097-0045. ; 79:11, s. 1338-1346
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic inflammation is thought to influence the risk of prostate cancer. The purpose of this population-based case-control study was to evaluate the association of 48 circulating inflammation markers with prostate cancer, to identify candidate markers for further investigation.METHODS: Serum samples collected from 235 prostate cancer patients and 198 population-based controls recruited in Örebro County, Sweden, in 1989-1991, were assessed using a multiplex bead-based immunoassay to determine concentrations of 48 circulating inflammation markers. Logistic regression was first used to evaluate the association between individual markers (highest vs lowest concentration quartile) and prostate cancer in unadjusted and mutually adjusted models. Second, patients with inflammatory conditions, metastatic or advanced prostate cancer, were excluded to address the possible influence of systemic disease on inflammation markers.RESULTS: Individual analyses first identified 21 markers associated with prostate cancer (P < .05), which after mutual adjustment were reduced to seven markers. After the exclusion of men with conditions linked with systemic inflammation, associations between prostate cancer and deviant levels of C-X3-C motif chemokine ligand 1, platelet-derived growth factor subunit B homodimer, interleukin 10, C-C motif chemokine ligand (CCL) 21, and CCL11 remained statistically significant.CONCLUSIONS: In this explorative study, we identified candidate inflammation markers of possible importance for prostate cancer pathophysiology, for further evaluation in prospective studies.
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| 68. |
- Vikström, Anna C., et al.
(författare)
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Alcohol influence on acrylamide to glycidamide metabolism assessed with hemoglobin-adducts and questionnaire data
- 2010
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 58:3, s. 820-824
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Tidskriftsartikel (refereegranskat)abstract
- Our purpose was to investigate whether alcohol (ethanol) consumption could have an influence on the metabolism of acrylamide to glycidamide in humans exposed to acrylamide through food. We studied a subsample from a population-based case–control study of prostate cancer in Sweden (CAPS). Questionnaire data for alcohol intake estimates was compared to the ratio of hemoglobin-adduct levels for acrylamide and glycidamide, used as a measure of individual differences in metabolism. Data from 161 non-smoking men were processed with regard to the influence of alcohol on the metabolism of acrylamide to glycidamide. A negative, linear trend of glycidamide-adduct to acrylamide-adduct-level ratios with increasing alcohol intake was observed and the strongest association (p-value for trend = 0.02) was obtained in the group of men with the lowest adduct levels (⩽47 pmol/g globin) when alcohol intake was stratified by acrylamide-adduct levels. The observed trend is likely due to a competitive effect between ethanol and acrylamide as both are substrates for cytochrome P450 2E1. Our results, strongly indicating that ethanol influence metabolism of acrylamide to glycidamide, partly explain earlier observations of only low to moderate associations between questionnaire data on dietary acrylamide intake and hemoglobin-adduct levels.
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| 69. |
- Wang, Xinan, et al.
(författare)
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Impact of individual level uncertainty of lung cancer polygenic risk score (PRS) on risk stratification
- 2024
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Ingår i: Genome Medicine. - : BioMed Central (BMC). - 1756-994X. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although polygenic risk score (PRS) has emerged as a promising tool for predicting cancer risk from genome-wide association studies (GWAS), the individual-level accuracy of lung cancer PRS and the extent to which its impact on subsequent clinical applications remains largely unexplored.Methods: Lung cancer PRSs and confidence/credible interval (CI) were constructed using two statistical approaches for each individual: (1) the weighted sum of 16 GWAS-derived significant SNP loci and the CI through the bootstrapping method (PRS-16-CV) and (2) LDpred2 and the CI through posteriors sampling (PRS-Bayes), among 17,166 lung cancer cases and 12,894 controls with European ancestry from the International Lung Cancer Consortium. Individuals were classified into different genetic risk subgroups based on the relationship between their own PRS mean/PRS CI and the population level threshold.Results: Considerable variances in PRS point estimates at the individual level were observed for both methods, with an average standard deviation (s.d.) of 0.12 for PRS-16-CV and a much larger s.d. of 0.88 for PRS-Bayes. Using PRS-16-CV, only 25.0% of individuals with PRS point estimates in the lowest decile of PRS and 16.8% in the highest decile have their entire 95% CI fully contained in the lowest and highest decile, respectively, while PRS-Bayes was unable to find any eligible individuals. Only 19% of the individuals were concordantly identified as having high genetic risk (> 90th percentile) using the two PRS estimators. An increased relative risk of lung cancer comparing the highest PRS percentile to the lowest was observed when taking the CI into account (OR = 2.73, 95% CI: 2.12–3.50, P-value = 4.13 × 10−15) compared to using PRS-16-CV mean (OR = 2.23, 95% CI: 1.99–2.49, P-value = 5.70 × 10−46). Improved risk prediction performance with higher AUC was consistently observed in individuals identified by PRS-16-CV CI, and the best performance was achieved by incorporating age, gender, and detailed smoking pack-years (AUC: 0.73, 95% CI = 0.72–0.74). Conclusions: Lung cancer PRS estimates using different methods have modest correlations at the individual level, highlighting the importance of considering individual-level uncertainty when evaluating the practical utility of PRS.
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| 70. |
- Wilson, Kathryn M., et al.
(författare)
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Acrylamide exposure measured by food frequency questionnaire and hemoglobin adduct levels and prostate cancer risk in the Cancer of the Prostate in Sweden Study
- 2009
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Ingår i: International Journal of Cancer. - : WILEY-LISS. - 0020-7136 .- 1097-0215. ; 124:10, s. 2384-2390
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Tidskriftsartikel (refereegranskat)abstract
- Acrylamide, a probable human carcinogen, is formed during the cooking of many commonly consumed foods. Data are scant on whether dietary acrylamide represents an important cancer risk in humans. We studied the association between acrylamide and prostate cancer risk using 2 measures of acrylamide exposure: intake from a food frequency questionnaire (FFQ) and acrylamide adducts to hemoglobin. We also studied the correlation between these 2 exposure measures. We used data from the population-based case-control study Cancer of the Prostate in Sweden (CAPS). Dietary data was available for 1,499 cases and 1, 118 controls. Hemoglobin adducts of acrylamide were measured in blood samples from a subset of 170 cases and 161 controls. We calculated odds ratios (ORs) for the risk of prostate cancer in high versus low quantiles of acrylamide exposure using logistic regression. The correlation between FFQ acrylamide intake and acrylamide adducts in non-smokers was 0.25 (95% confidence interval: 0.14-0.35), adjusted for age, region, energy intake, and laboratory batch. Among controls the correlation was 0.35 (95% CI: 0.21-0.48); among cases it was 0.15 (95% CI: 0.00-0.30). The OR of prostate cancer for the highest versus lowest quartile of acrylamide adducts was 0.93 (95% CI: 0.47-1.85, p-value for trend = 0.98). For FFQ acrylamide, the OR of prostate cancer for the highest versus lowest quintile was 0.97 (95% CI: 0.75-1.27,p trend = 0.67). No significant associations were found between acrylamide exposure and risk of prostate cancer by stage, grade, or PSA level. Acrylamide adducts to hemoglobin and FFQ-measured acrylamide intake were moderately correlated. Neither measure of acrylamide exposure-hemoglobin adducts or FFQ-was associated with risk of prostate cancer. (C) 2008 Wiley-Liss. Inc.
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