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31.
  • Bentmar Holgersson, Magdalena, et al. (författare)
  • Androgen receptor polymorphism dependent variation in prostate specific antigen concentrations of European men.
  • 2014
  • Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 23:10, s. 2048-2056
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Androgens acting via the androgen receptor (AR) stimulate production of prostate specific antigen (PSA), which is a clinical marker of prostate cancer (PCa). Since genetic variants in the AR may have a significant impact on the risk of being diagnosed with PCa, the aim was to investigate if AR-variants were associated with the risk of having PSA above clinically used cut-off thresholds of 3 or 4 ng/mL in men without PCa. Methods Men without PCa history (n=1744) were selected from the European Male Ageing Study (EMAS) cohort of 40-80 year old men from 8 different European centers. Using linear and logistic regression models, with age and center as covariates, we investigated whether AR-variants (CAG repeat-length and/or SNP genotype) were associated with having serum PSA concentrations above 3 or 4 ng/mL, which often are set as cut-off concentrations for further investigation of PCa. Results Carriers of the SNP rs1204038 A-allele (16% of the men) were more likely to have PSA>3 and 4 ng/mL (OR; 95%CI 1.65; 1.13-2.40 and 1.87; 1.18-2.96, respectively) than G-allele carriers. They also had shorter CAG-repeats (median 20 vs. 23, p<0.0005), but CAG repeat length per se did not affect the PSA concentrations. Conclusion The A-allele of the SNP rs1204038 gives a 65% higher risk of having PSA above 3 ng/mL than the G-allele in men without PCa, and thereby an increased risk of being referred for further examination on suspicion of PCa. Impact Serum PSA as a clinical marker could be improved by adjustment for AR-genotype.
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32.
  • Bethke, Lara, et al. (författare)
  • Functional polymorphisms in folate metabolism genes influence the risk of meningioma and glioma
  • 2008
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 17:5, s. 1195-1202
  • Tidskriftsartikel (refereegranskat)abstract
    • Folate metabolism plays an important role in carcinogenesis. To test the hypothesis that polymorphic variation in the folate metabolism genes 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and methionine synthase reductase (MTR) influences the risk of primary brain tumors, we genotyped 1,005 glioma cases, 631 meningioma cases, and 1,101 controls for the MTHFR C677A and A1298C, MTRR A66G, and MTR A2756G variants. MTHFR C677T-A1298C diplotypes were associated with risk of meningioma (P = 0.002) and glioma (P = 0.02); risks were increased with genotypes associated with reduced MTHFR activity. The highest risk of meningioma was associated with heterozygosity for both MTHFR variants [odds ratio (OR), 2.11; 95% confidence interval (95% CI), 1.42-3.12]. The corresponding OR for glioma was 1.23 (95% CI, 0.91-1.66). A significant association between risk of meningioma and homozygosity for MTRR 66G was also observed (OR, 1.41; 95% CI, 1.02-1.94). Our findings provide support for the role of folate metabolism in the development of primary brain tumors. In particular, genotypes associated with increased 5,10-methylenetetrahydrofolate levels are associated with elevated risk.
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33.
  • Bethke, Lara, et al. (författare)
  • The Common D302H Variant of CASP8 Is Associated with Risk of Glioma
  • 2008
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 17:4, s. 987-989
  • Tidskriftsartikel (refereegranskat)abstract
    • Caspase 8 (CASP8) is a key regulator of apoptosis or programmed cell death, and, hence, a defense against cancer. We tested the hypothesis that the CASP8 polymorphism D302H influences risk of glioma through analysis of five series of glioma case patients and controls (n = 1,005 and 1,011, respectively). Carrier status for the rare allele of D302H was associated with a 1.37-fold increased risk (95% confidence interval, 1.10-1.70; P = 0.004). The association of CASP8 D302H with glioma risk indicates the importance of inherited variation in the apoptosis pathway in susceptibility to this form of primary brain tumor.
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34.
  • Biermann, Jana, et al. (författare)
  • A novel 18-marker panel predicting clinical outcome in breast cancer
  • 2017
  • Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1538-7755. ; 26:11, s. 1619-28
  • Tidskriftsartikel (refereegranskat)abstract
    • Gene expression profiling has made considerable contributions to our understanding of cancer biology and clinical care. This study describes a novel gene expression signature for breast cancer-specific survival that was validated using external datasets. Gene expression signatures for invasive breast carcinomas (mainly Luminal B subtype) corresponding to 136 patients were analysed using Cox regression and the effect of each gene on disease-specific survival (DSS) was estimated. Iterative Bayesian Model Averaging was applied on multivariable Cox regression models resulting in an 18-marker panel, which was validated using three external validation datasets. The 18 genes were analysed for common pathways and functions using the Ingenuity Pathway Analysis software. This study complied with the REMARK criteria. The 18-gene multivariable model showed a high predictive power for DSS in the training and validation cohort and a clear stratification between high- and low-risk patients. The differentially expressed genes were predominantly involved in biological processes such as cell cycle, DNA replication, recombination, and repair. Furthermore, the majority of the 18 genes were found to play a pivotal role in cancer. Our findings demonstrated that the 18 molecular markers were strong predictors of breast cancer-specific mortality. The stable time-dependent area under the ROC curve function (AUC(t)) and high C-indices in the training and validation cohorts were further improved by fitting a combined model consisting of the 18-marker panel and established clinical markers. Our work supports the applicability of this 18-marker panel to improve clinical outcome prediction for breast cancer patients.
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35.
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36.
  • Bjørge, Tone, et al. (författare)
  • Metabolic syndrome and breast cancer in the me-can (metabolic syndrome and cancer) project.
  • 2010
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 19:7, s. 1737-1745
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Few studies have assessed the metabolic syndrome (MetS) as an entity in relation to breast cancer risk, and results have been inconsistent. We aimed to examine the association between MetS factors (individually and combined) and risk of breast cancer incidence and mortality. METHODS: Two hundred ninety thousand women from Austria, Norway, and Sweden were enrolled during 1974-2005, with measurements of height, weight, blood pressure, and levels of glucose, cholesterol, and triglycerides. Relative risks (RR) of breast cancer were estimated using Cox proportional hazards regression for each MetS factor in quintiles and for standardized levels (z-scores) and for a composite z-score for the MetS. RESULTS: There were 4,862 incident cases of breast cancer and 633 deaths from breast cancer identified. In women below age 50, there was a decreased risk of incident cancer for the MetS (per 1-unit increment of z-score; RR, 0.83; 95% confidence interval, 0.76-0.90) as well as for the individual factors (except for glucose). The lowest risks were seen among the heaviest women. In women above age 60, there was an increased risk of breast cancer mortality for the MetS (RR, 1.23; 95% confidence interval, 1.04-1.45) and for blood pressure and glucose. The strongest association with mortality was seen for increased glucose concentrations. CONCLUSIONS: The MetS was associated with a decreased risk of incident breast cancer in women below age 50 with high body mass index, and with an increased risk of breast cancer mortality in women above 60. IMPACT: Lifestyle interventions as recommended for cardiovascular disease prevention may be of value to prevent breast cancer mortality in postmenopausal women.
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37.
  • Blom, Johannes, et al. (författare)
  • A 9-year follow-up study of participants and nonparticipants in sigmoidoscopy screening : importance of self-selection
  • 2008
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 17:5, s. 1163-1168
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Self-selection may compromise cost-effectiveness of screening programs. We hypothesized that nonparticipants have generally higher morbidity and mortality than participants. METHODS: A Swedish population-based random sample of 1,986 subjects ages 59 to 61 years was invited to sigmoidoscopy screening and followed up for 9 years by means of multiple record linkages to health and population registers. Gender-adjusted cancer incidence rate ratio (IRR) and overall and disease group-specific and mortality rate ratio (MRR) with 95% confidence intervals (95% CI) were estimated for nonparticipants relative to participants. Cancer and mortality rates were also estimated relative to the age-matched, gender-matched, and calendar period-matched Swedish population using standardized incidence ratios and standardized mortality ratios. RESULTS: Thirty-nine percent participated. The incidence of colorectal cancer (IRR, 2.2; 95% CI, 0.8-5.9), other gastrointestinal cancer (IRR, 2.7; 95% CI, 0.6-12.8), lung cancer (IRR, 2.2; 95% CI, 0.8-5.9), and smoking-related cancer overall (IRR, 1.4; 95% CI, 0.7-2.5) tended to be increased among nonparticipants relative to participants. Standardized incidence ratios for most of the studied cancers tended to be >1.0 among nonparticipants and <1.0 among participants. Mortality from all causes (MRR, 2.4; 95% CI, 1.7-3.4), neoplastic diseases (MRR, 1.9; 95% CI, 1.1-3.5), gastrointestinal cancer (MRR, 4.7; 95% CI, 1.1-20.7), and circulatory diseases (MRR, 2.3; 95% CI, 1.2-4.2) was significantly higher among nonparticipants than among participants. Standardized mortality ratio for the studied outcomes tended to be increased among nonparticipants and was generally decreased among participants. CONCLUSION: Individuals who might benefit most from screening are overrepresented among nonparticipants. This self-selection may attenuate the cost-effectiveness of screening programs on a population level.
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38.
  • Bodén, Stina, et al. (författare)
  • C-reactive Protein and Future Risk of Clinical and Molecular Subtypes of Colorectal Cancer
  • 2020
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 29:7, s. 1482-1491
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Inflammation has been implicated in colorectal cancer etiology, but the relationship between C-reactive protein (CRP) and colorectal cancer risk is unclear. We aimed to investigate the association between prediagnostic plasma CRP concentrations and the risk of clinical and molecular colorectal cancer subtypes.Methods: We used prospectively collected samples from 1,010 matched colorectal cancer case-control pairs from two population-based cohorts in Northern Sweden, including 259 with repeated samples. Conditional logistic regression and linear mixed models were used to estimate relative risks of colorectal cancer, including subtypes based on BRAF and KRAS mutations, microsatellite instability status, tumor location, stage, lag time, and (using unconditional logistic regression) body mass index.Results: CRP was not associated with colorectal cancer risk, regardless of clinical or molecular colorectal cancer subtype. For participants with advanced tumors and blood samples <5 years before diagnosis, CRP was associated with higher risk [OR per 1 unit increase in natural logarithm (In) transformed CRP, 1.32; 95% confidence interval (CI), 1.01-1.73]. CRP levels increased over time, but average time trajectories were similar for cases and controls (P-interaction = 0.19).Conclusions: Our results do not support intertumoral heterogeneity as an explanation for previous inconsistent findings regarding the role of CRP in colorectal cancer etiology. The possible association in the subgroup with advanced tumors and shorter follow-up likely reflects undiagnosed cancer at baseline. Impact: Future efforts to establish the putative role of chronic, low-grade inflammation in colorectal cancer development will need to address the complex relationship between systemic inflammatory factors and tumor microenvironment, and might consider larger biomarker panels than CRP alone.
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39.
  • Bolejko, Anetta, et al. (författare)
  • Prevalence, Long-term Development, and Predictors of Psychosocial Consequences of False-Positive Mammography among Women Attending Population-Based Screening
  • 2015
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 24:9, s. 1388-1397
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cancer screening aims to detect cancer at an asymptomatic stage, although side effects from screening also occur. We investigated the prevalence, longitudinal development, and predictors of psychosocial consequences of false-positive breast cancer screening. METHODS: Three hundred ninety-nine women with false-positive screening mammography responded to the Consequences of Screening-Breast Cancer (COS-BC) questionnaire immediately after a negative diagnosis (free from breast cancer) following recall examination(s) (baseline), and 6 and 12 months later. Age-matched controls (n = 499) with a negative mammogram responded to the COS-BC at the same occasions. Five COS-BC scales (Sense of dejection, Anxiety, Behavioral, Sleep, and Existential values) were used as outcome measures. RESULTS: Women with false-positive mammography had consistently higher prevalence of all five consequences compared with controls (P < 0.001). The prevalences decreased between baseline and 6 months (P < 0.001) but were stable between 6 and 12 months (P ≥ 0.136). Early recall profoundly predicted long-term consequences for all five outcomes (OR, 3.05-10.31), along with dissatisfaction with information at recall (OR, 2.28-2.56), being foreign-born (OR, 2.35-3.71), and lack of social support (OR, 1.13-1.25). CONCLUSION: This 1-year longitudinal study shows that women experience psychosocial consequences of false-positive screening mammography. Early recall should be performed cautiously, and provision of information as well as social support may reduce psychosocial consequences. IMPACT: Although delivery of population-based screening reduces breast cancer mortality, it also raises the issue of its impact on the psychosocial well-being of healthy women. Our findings identify predictors that can be targeted in future efforts to reduce the side effects of mammographic screening.
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40.
  • Bonn, S. E., et al. (författare)
  • Physical Activity and Survival among Men Diagnosed with Prostate Cancer
  • 2015
  • Ingår i: Cancer Epidemiology Biomarkers & Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 24:1, s. 57-64
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Few studies have investigated the association between post-diagnosis physical activity and mortality among men diagnosed with prostate cancer. The aim of this study was to investigate the effect of physical activity after a prostate cancer diagnosis on both overall and prostate cancer-specific mortality in a large cohort. Methods: Data from 4,623 men diagnosed with localized prostate cancer 1997-2002 and followed-up until 2012 were analyzed. HRs with 95% confidence intervals (CI) were estimated using Cox proportional hazards models to examine the association between post-diagnosis recreational MET-h/d, time spent walking/bicycling, performing household work or exercising, and time to overall and prostate cancer-specific death. All models were adjusted for potential confounders. Results: During the follow-up, 561 deaths of any cause and 194 deaths from prostate cancer occurred. Statistically significantly lower overall mortality rates were found among men engaged in 5 recreationalMET-h/d (HR, 0.63; 95% CI, 0.52-0.77), walking/ bicycling 20 min/d (HR, 0.70; 95% CI, 0.57-0.86), performing householdwork > 1 h/d (HR, 0.71; 95% CI, 0.59-0.86), or exercising > 1 h/wk (HR, 0.74; 95% CI, 0.61-0.90), compared with less active men within each activity type. For prostate cancer-specific mortality, statistically significantly lower mortality rates were seen among men walking/bicycling >= 20 min/d (HR, 0.61; 95% CI, 0.43-0.87) or exercising 1 h/wk (HR, 0.68; 95% CI, 0.48-0.94). Conclusions: Higher levels of physical activity were associated with reduced rates of overall and prostate cancer-specific mortality. Impact: Our study further strengthens previous results indicating beneficial effects of physical activity on survival among men with prostate cancer.
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