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1.
  • Möller, Elisabeth, et al. (författare)
  • Mediterranean Diet Score and prostate cancer risk in a Swedish population-based case-control study
  • 2013
  • Ingår i: Journal of Nutritional Science. - 2048-6790 .- 2048-6790. ; 2
  • Tidskriftsartikel (refereegranskat)abstract
    • Several individual components of the Mediterranean diet have been shown to offer protection against prostate cancer. The present study is the first to investigate the association between adherence to the Mediterranean diet and the relative risk of prostate cancer. We also explored the usefulness of the Mediterranean Diet Score (MDS) in a non-Mediterranean population. FFQ data were obtained from 1482 incident prostate cancer patients and 1108 population-based controls in the Cancer of the Prostate in Sweden (CAPS) study. We defined five MDS variants with different components or using either study-specific intakes or intakes in a Greek reference population as cut-off values between low and high intake of each component. Unconditional logistic regression was used to estimate the relative risk of prostate cancer for high and medium v. low MDS, as well as potential associations with the individual score components. No statistically significant association was found between adherence to the Mediterranean diet based on any of the MDS variants and prostate cancer risk (OR range: 0·96-1·19 for total prostate cancer, comparing high with low adherence). Overall, we found little support for an association between the Mediterranean diet and prostate cancer in this Northern European study population. Despite potential limitations inherent in the study or in the build-up of a dietary score, we suggest that the original MDS with study-specific median intakes as cut-off values between low and high intake is useful in assessing the adherence to the Mediterranean diet in non-Mediterranean populations.
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2.
  • Adams, Charleen, et al. (författare)
  • Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study.
  • 2018
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755.
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).MATERIALS AND METHODS: The case-control portion of the study was conducted in nine UK centres with men aged 50-69 years who underwent prostate-specific antigen (PSA) screening for prostate cancer within the Prostate testing for cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (p <0.0014, multiple-testing threshold). These fell into four classes: i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); ii) fatty acids and ratios; iii) amino acids; iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.
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3.
  • Davidsson, Sabina, et al. (författare)
  • Inflammation, focal atrophic lesions, and prostatic intraepithelial neoplasia with respect to risk of lethal prostate cancer
  • 2011
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 20:10, s. 2280-2287
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A challenge in prostate cancer (PCa) management is identifying potentially lethal disease at diagnosis. Inflammation, focal prostatic atrophy, and prostatic intraepithelial neoplasia (PIN) are common in prostate tumor specimens, but it is not clear whether these lesions have prognostic significance. Methods: We conducted a case-control study nested in a cohort of men diagnosed with stage T1a-b PCa through transurethral resection of the prostate in Sweden. Cases are men who died of PCa (n = 228). Controls are men who survived more than 10 years after PCa diagnosis without metastases (n = 387). Slides were assessed for Gleason grade, inflammation, PIN, and four subtypes of focal prostatic atrophy: simple atrophy (SA), postatrophic hyperplasia (PAH), simple atrophy with cyst formation, and partial atrophy. We estimated OR and 95% CI for odds of lethal PCa with multivariable logistic regression. Results: Chronic inflammation and PIN were more frequently observed in tumors with PAH, but not SA. No specific type of atrophy or inflammation was significantly associated with lethal PCa overall, but there was a suggestion of a positive association for chronic inflammation. Independent of age, Gleason score, year of diagnosis, inflammation, and atrophy type, men with PIN were 89% more likely to die of PCa (95% CI: 1.04-3.42). Conclusion: Our data show that PIN, and perhaps presence of moderate or severe chronic inflammation, may have prognostic significance for PCa. Impact: Lesions in tumor adjacent tissue, and not just the tumor itself, may aid in identification of clinically relevant disease. Cancer Epidemiol Biomarkers Prev; 20(10); 2280-7. (C) 2011 AACR.
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4.
  • Downer, Mary K., et al. (författare)
  • Dairy intake in relation to prostate cancer survival
  • 2017
  • Ingår i: International Journal of Cancer. - Hoboken : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 140:9, s. 2060-2069
  • Tidskriftsartikel (refereegranskat)abstract
    • Dairy intake has been associated with increased risk of advanced prostate cancer. Two US cohort studies reported increased prostate cancer-specific mortality with increased high-fat milk intake. We examined whether dairy and related nutrient intake were associated with prostate cancer progression in a Swedish patient population with high dairy consumption. We prospectively followed 525 men with newly diagnosed prostate cancer (diagnosed 1989-1994). We identified and confirmed deaths through February 2011 (n = 222 prostate cancer-specific, n = 268 from other causes). Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between food or nutrient intake and prostate cancer-specific death. On average, patients consumed 5.0 servings/day of total dairy products at diagnosis. In the whole population, high-fat milk intake was not associated with prostate cancer-specific death (95% CI: 0.78, 2.10; p-trend = 0.32; multivariate-adjusted model). However, among patients diagnosed with localized prostate cancer, compared to men who consumed <1 servings/day of high-fat milk, those who drank >= 3 servings/day had an increased hazard of prostate cancer mortality (HR = 6.10; 95% CI: 2.14, 17.37; p-trend = 0.004; multivariate-adjusted model). Low-fat milk intake was associated with a borderline reduction in prostate cancer death among patients with localized prostate cancer. These associations were not observed among patients diagnosed with advanced stage prostate cancer. Our data suggest a positive association between high-fat milk intake and prostate cancer progression among patients diagnosed with localized prostate cancer. Further studies are warranted to investigate this association and elucidate the mechanisms by which high-fat milk intake may promote prostate cancer progression.
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5.
  • Jiang, X., et al. (författare)
  • Shared heritability and functional enrichment across six solid cancers
  • 2019
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
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6.
  • Lagerros, Y. T., et al. (författare)
  • Validity and reliability of self-reported total energy expenditure using a novel instrument
  • 2006
  • Ingår i: European Journal of Epidemiology. - Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Milano Bicocca, Dept Stat, Milan, Italy. Royal Inst Technol, Sch Comp Sci & Commun, Stockholm, Sweden. : SPRINGER. - 0393-2990 .- 1573-7284. ; 21:3, s. 227-236
  • Tidskriftsartikel (refereegranskat)abstract
    • Improved methods for quantitative self-reports of total physical activity in epidemiological studies are needed. We evaluated randomly selected individuals' ability to integrate their perception of physical activity over time to produce an estimate of the usual level, using a novel instrument for self-quantification of energy expenditure. A population-based sample of 418 Swedish men and women, age 20-59, completed a questionnaire containing the new instrument. For validation, three 24 hour recalls by phone served as gold standard. Reproducibility was assessed through administering the instrument another three times. The validation involved 133 subjects and another 160 completed the reproducibility evaluation. Pearson correlation between usual daily energy expenditure measured by the instrument and the mean of the 24 hour recalls was 0.73. After subdividing the self-reported daily energy expenditure and the mean of the 24 hour recalls into quintiles, 83.5% of the participants remained in the same quintile, or one quintile apart. There was a tendency towards overestimation of usual daily physical activity. This was significantly associated with low education. Reproducibility showed an intraclass correlation of 0.55. Although integrated reports of usual daily energy expenditure over longer periods seem to be afflicted with a tendency of overestimation, total energy expenditure can be estimated with reasonable validity and reproducibility using our instrument.
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8.
  • Penney, K. L., et al. (författare)
  • mRNA expression signature of Gleason grade predicts lethal prostate cancer
  • 2011
  • Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 29:17, s. 2391-2396
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Prostate-specific antigen screening has led to enormous overtreatment of prostate cancer because of the inability to distinguish potentially lethal disease at diagnosis. We reasoned that by identifying an mRNA signature of Gleason grade, the best predictor of prognosis, we could improve prediction of lethal disease among men with moderate Gleason 7 tumors, the most common grade, and the most indeterminate in terms of prognosis.PATIENTS AND METHODS: Using the complementary DNA-mediated annealing, selection, extension, and ligation assay, we measured the mRNA expression of 6,100 genes in prostate tumor tissue in the Swedish Watchful Waiting cohort (n = 358) and Physicians' Health Study (PHS; n = 109). We developed an mRNA signature of Gleason grade comparing individuals with Gleason ≤ 6 to those with Gleason ≥ 8 tumors and applied the model among patients with Gleason 7 to discriminate lethal cases.RESULTS: We built a 157-gene signature using the Swedish data that predicted Gleason with low misclassification (area under the curve [AUC] = 0.91); when this signature was tested in the PHS, the discriminatory ability remained high (AUC = 0.94). In men with Gleason 7 tumors, who were excluded from the model building, the signature significantly improved the prediction of lethal disease beyond knowing whether the Gleason score was 4 + 3 or 3 + 4 (P = .006).CONCLUSION: Our expression signature and the genes identified may improve our understanding of the de-differentiation process of prostate tumors. Additionally, the signature may have clinical applications among men with Gleason 7, by further estimating their risk of lethal prostate cancer and thereby guiding therapy decisions to improve outcomes and reduce overtreatment.
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9.
  • Pettersson, Andreas, et al. (författare)
  • The ABC model of prostate cancer : A conceptual framework for the design and interpretation of prognostic studies.
  • 2017
  • Ingår i: Cancer. - Hoboken, USA : John Wiley & Sons. - 0008-543X .- 1097-0142. ; 123:9, s. 1490-1496
  • Tidskriftsartikel (refereegranskat)abstract
    • There has been limited success in identifying prognostic biomarkers in prostate cancer. A partial explanation may be that insufficient emphasis has been put on clearly defining what type of marker or patient category a biomarker study aims to identify and how different cohort characteristics affect the ability to identify such a marker. In this article, the authors put forth the ABC model of prostate cancer, which defines 3 groups of patients with localized disease that an investigator may seek to identify: patients who, within a given time frame, will not develop metastases even if untreated (category A), will not develop metastases because of radical treatment (category B), or will develop metastases despite radical treatment (category C). The authors demonstrate that follow-up time and prostate-specific antigen screening intensity influence the prevalence of patients in categories A, B, and C in a study cohort, and that prognostic markers must be tested in both treated and untreated cohorts to accurately distinguish the 3 groups. The authors suggest that more emphasis should be put on considering these factors when planning, conducting, and interpreting the results from prostate cancer biomarker studies, and propose the ABC model as a framework to aid in that process. Cancer 2017;123:1490-1496. © 2017 American Cancer Society.
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10.
  • Sboner, Andrea, et al. (författare)
  • Molecular sampling of prostate cancer : a dilemma for predicting disease progression
  • 2010
  • Ingår i: BMC Medical Genomics. - London, United Kingdom : BioMed Central. - 1755-8794 .- 1755-8794. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Current prostate cancer prognostic models are based on pre-treatment prostate specific antigen (PSA) levels, biopsy Gleason score, and clinical staging but in practice are inadequate to accurately predict disease progression. Hence, we sought to develop a molecular panel for prostate cancer progression by reasoning that molecular profiles might further improve current clinical models.Methods: We analyzed a Swedish Watchful Waiting cohort with up to 30 years of clinical follow up using a novel method for gene expression profiling. This cDNA-mediated annealing, selection, ligation, and extension (DASL) method enabled the use of formalin-fixed paraffin-embedded transurethral resection of prostate (TURP) samples taken at the time of the initial diagnosis. We determined the expression profiles of 6100 genes for 281 men divided in two extreme groups: men who died of prostate cancer and men who survived more than 10 years without metastases (lethals and indolents, respectively). Several statistical and machine learning models using clinical and molecular features were evaluated for their ability to distinguish lethal from indolent cases.Results: Surprisingly, none of the predictive models using molecular profiles significantly improved over models using clinical variables only. Additional computational analysis confirmed that molecular heterogeneity within both the lethal and indolent classes is widespread in prostate cancer as compared to other types of tumors.Conclusions: The determination of the molecularly dominant tumor nodule may be limited by sampling at time of initial diagnosis, may not be present at time of initial diagnosis, or may occur as the disease progresses making the development of molecular biomarkers for prostate cancer progression challenging.
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