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  • Hagel, Eva, et al. (författare)
  • PCBaSe Sweden: A register-based resource for prostate cancer research
  • 2009
  • Ingår i: Scandinavian Journal of Urology and Nephrology1967-01-01+01:002013-01-01+01:00. - Taylor & Francis. - 0036-5599. ; 43:5, s. 342-349
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To construct a database for clinical epidemiological prostate cancer research based on linkages between the National Prostate Cancer Register (NPCR) of Sweden, a population-based, nationwide quality database, and other nationwide registries. Material and methods. By use of the individually unique Swedish Personal Identity Number, the NPCR was linked to the Swedish Cancer Registry, the Cause of Death Register, the Prescribed Drug Register, the National Patient Register and the Acute Myocardial Infarction Register, all held at the Centre for Epidemiology at the National Board of Health and Welfare, and the Register of the Total Population, the Longitudinal Integration Database for Health Insurance and Labor Market Studies and the Multi-Generation Register, held at Statistics Sweden, and to the Swedish Hernia Register. Results. Record linkages between the NPCR and the Swedish Cancer Registry, the Cause of Death Register and the Register of the Total Population generated a database, named PCBaSe Sweden, including 80 079 prostate cancer cases, diagnosed between 1 January 1996 and 31 December 2006. Record linkage between PCBaSe Sweden and the Prescribed Drug Register generated 59 721 unique matches and linkage to the Acute Myocardial Infarction Register resulted in 11 459 matches. Conclusion. PCBaSe Sweden is a newly created and unique database with over 80 000 cases of prostate cancer with comprehensive data on inpatient and outpatient care, patterns of use of prescribed drugs and socioeconomic and familial factors. Many topics in clinical prostate cancer epidemiology can be investigated. using PCBaSe Sweden.
  • Stocks, Tanja, 1977-, et al. (författare)
  • Blood glucose and risk of incident and fatal cancer in the metabolic syndrome and cancer project (Me-Can) analysis of six prospective cohorts.
  • 2009
  • Ingår i: PLoS Medicine. - 1549-1277. ; 6:12, s. e1000201
  • Tidskriftsartikel (refereegranskat)abstract
    •  BackgroundProspective studies have indicated that elevated blood glucose levels may increase the risk of cancer, but the strength of the association is unclear. We examined the association between blood glucose and cancer risk in a prospective study of six European cohorts. Methods and Findings The Metabolic syndrome and Cancer project (Me-Can) includes cohorts from Norway, Austria, and Sweden; the current study included 274,126 men and 275,818 women. Mean age at baseline was 44.8 years and mean follow-up time was 10.4 years. Excluding the first year of follow-up, 18,621 men and 11,664 women were diagnosed with cancer, and 6,973 men and 3,088 women died of cancer. We used Cox regression models to calculate relative risk (RR) for glucose levels, and included adjustment for body mass index (BMI) and smoking  status in the analyses. RRs were corrected for regression dilution ratio of glucose. RR (95% confidence interval) per 1 mmol/l increment of glucose for overall incident cancer was 1.05 (1.01-1.10) in men and 1.11 (1.05-1.16) in women, and corresponding RRs for fatal cancer were 1.15 (1.07-1.22) and 1.21 (1.11-1.33), respectively. Significant increases in risk among men were found for incident and fatal cancer of the liver, gallbladder and respiratory tract, for incident thyroid cancer and multiple myeloma, and for fatal rectal cancer. In women, significant associations were found for incident and fatal cancer of the pancreas, for incident urinary bladder cancer, and for fatal cancer of the uterine corpus, cervix uteri, and stomach.ConclusionsData from our study indicate that abnormal glucose metabolism, independently of BMI, is associated with an increased risk of cancer overall and at several cancer sites. Our data showed stronger associations among women than among men, and for fatal cancer compared to incident cancer. 
  • Borena, Wegene, et al. (författare)
  • Long-term temporal trends in cardiovascular and metabolic risk factors
  • 2009
  • Ingår i: Wiener Klinische Wochenschrift. - Springer. - 1613-7671. ; 121:19-20, s. 623-630
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Metabolic factors such as obesity, hypertension, dyslipidemia and hyperglycemia have consistently been associated with increased risk of cardiovascular disease. There is also growing evidence that these factors are linked to cancer incidence and mortality. The aim of this study was to investigate long-term trends in major metabolic risk factors in three large cohorts. MATERIALS AND METHODS: Data from 239,602 individuals aged 25-64 years participating in health examinations between 1976 and 2005 were used to estimate prevalence and trends in five risk factors. RESULTS: Irrespective of geographic location, individual metabolic risk factors showed divergent trends across the observation period. Whereas obesity and hyperglycemia in men increased by a per decade ratio of 1.54 (95% CI: 1.42-1.66) and 1.62 (95% CI: 1.49-1.76), respectively, and in women by 1.48 (95% CI: 1.41-1.56) and 1.66 (95% CI: 1.57-1.75), hypertension decreased by 0.71 (95% CI: 0.68-0.74) in men and 0.83 (95% CI: 0.79-0.86) in women. Dyslipidemia increased from the 1970s to the 1980s but declined in the succeeding decade. A combination of three or more of these risk factors increased significantly in men by a ratio of 1.15 (95% CI: 1.08-1.22) per decade and in women by 1.20 (95% CI: 1.15-1.27). CONCLUSION: The study shows that individual metabolic risk factors followed divergent trends over the period of three decades even though the combination of three or more risk factors used as a proxy for the metabolic syndrome appeared to be stable over the last two of the decades. The two key components of the syndrome, namely BMI and glucose levels, increased significantly and deserve professional attention.
  • Ahn, Jiyoung, et al. (författare)
  • Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3).
  • 2009
  • Ingår i: Human molecular genetics. - 1460-2083. ; 18:19, s. 3749-57
  • Tidskriftsartikel (refereegranskat)abstract
    • Twin studies suggest a heritable component to circulating sex steroid hormones and sex hormone-binding globulin (SHBG). In the NCI-Breast and Prostate Cancer Cohort Consortium, 874 SNPs in 37 candidate genes in the sex steroid hormone pathway were examined in relation to circulating levels of SHBG (N = 4720), testosterone (N = 4678), 3 alpha-androstanediol-glucuronide (N = 4767) and 17beta-estradiol (N = 2014) in Caucasian men. rs1799941 in SHBG is highly significantly associated with circulating levels of SHBG (P = 4.52 x 10(-21)), consistent with previous studies, and testosterone (P = 7.54 x 10(-15)), with mean difference of 26.9 and 14.3%, respectively, comparing wild-type to homozygous variant carriers. Further noteworthy novel findings were observed between SNPs in ESR1 with testosterone levels (rs722208, mean difference = 8.8%, P = 7.37 x 10(-6)) and SRD5A2 with 3 alpha-androstanediol-glucuronide (rs2208532, mean difference = 11.8%, P = 1.82 x 10(-6)). Genetic variation in genes in the sex steroid hormone pathway is associated with differences in circulating SHBG and sex steroid hormones.
  • Cust, Anne E, et al. (författare)
  • The influence of overweight and insulin resistance on breast cancer risk and tumour stage at diagnosis : a prospective study.
  • 2009
  • Ingår i: Breast Cancer Research and Treatment. - Springer. - 0167-6806. ; 113:3, s. 567-576
  • Tidskriftsartikel (refereegranskat)abstract
    • It is hypothesized that insulin resistance and related metabolic factors may influence breast cancer risk, however the epidemiological evidence remains inconclusive. We conducted a case–control study nested in a prospective cohort in Northern Sweden, to clarify the associations of body mass index (BMI), leptin, adiponectin, C-peptide, and glycated haemoglobin (HbA1c) with breast cancer risk. We also investigated whether these associations may be modified by age at diagnosis, tumour stage, and oestrogen and progesterone receptor status. During follow-up, 561 women developed invasive breast cancer and 561 matched controls were selected. Conditional logistic regression was used to calculate odds ratios (OR) as estimates of relative risk, and 95% confidence intervals (CI). The associations of BMI, leptin and HbA1c with breast cancer risk differed significantly according to whether the tumour was diagnosed as stage I or stage II–IV (P heterogeneity all <0.05). These factors were significantly inversely associated with risk in the group of stage I tumours, with ORs for top vs. bottom tertile for BMI of 0.48 (95% CI, 0.30–0.78, P trend = 0.004); leptin, 0.64 (95% CI, 0.41–1.00, P trend = 0.06); and HbA1c, 0.47 (95% CI, 0.28–0.80, P trend = 0.005). For stage II–IV tumours, there was a suggestion of an increased risk with higher levels of these factors. There were no significant differences in the associations of BMI, leptin, adiponectin, C-peptide and HbA1c with breast cancer risk in subgroups of age at diagnosis or tumour receptor status. This prospective study suggests that BMI, leptin and HbA1c influence breast tumour initiation and progression.
  • Holmström, Benny, 1974-, et al. (författare)
  • Prostate specific antigen for early detection of prostate cancer : longitudinal study
  • 2009
  • Ingår i: BMJ (Clinical research ed.). - 1468-5833. ; 339, s. b3537
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To evaluate if prostate specific antigen test attains validity standards required for screening in view of recent prostate cancer screening trial results.DESIGN: Case-control study nested in longitudinal cohort.SETTING: Västerbotten Intervention Project cohort, Umeå, Sweden.PARTICIPANTS: 540 cases and 1034 controls matched for age and date of blood draw.MAIN OUTCOME MEASURE: Validity of prostate specific antigen for prediction of subsequent prostate cancer diagnosis by record linkage to cancer registry.RESULTS: Blood samples were drawn on average 7.1 (SD 3.7) years before diagnosis. The area under the curve for prostate specific antigen was 0.84 (95% confidence interval 0.82 to 0.86). At prostate specific antigen cut-off values of 3, 4, and 5 ng/ml, sensitivity estimates were 59%, 44%, and 33%, and specificity estimates were 87%, 92%, and 95%. The positive likelihood ratio commonly considered to "rule in disease" is 10; in this study the positive likelihood ratios were 4.5, 5.5, and 6.4 for prostate specific antigen cut-off values of 3, 4, and 5 ng/ml. The negative likelihood ratio commonly considered to "rule out disease" is 0.1; in this study the negative likelihood ratios were 0.47, 0.61, and 0.70 for prostate specific antigen cut-off values of 3, 4, and 5 ng/ml. For a cut-off of 1.0 ng/ml, the negative likelihood ratio was 0.08.CONCLUSIONS: No single cut-off value for prostate specific antigen concentration attained likelihood ratios formally required for a screening test. Prostate specific antigen concentrations below 1.0 ng/ml virtually ruled out a prostate cancer diagnosis during the follow-up. Additional biomarkers for early detection of prostate cancer are needed before population based screening for prostate cancer should be introduced.
  • Holmström, Benny, et al. (författare)
  • PSA-testet håller inte för screening : bra – men inte tillräckligt bra
  • 2009
  • Ingår i: Läkartidningen. - 0023-7205. ; 107:7, s. 436, 438-439
  • Tidskriftsartikel (refereegranskat)abstract
    • Prostatacancer är den vanligaste cancersjukdomen och den vanligaste cancerrelaterade dödsorsaken bland män i Sverige. Screening för prostataspecifikt antigen (PSA) minskade dödligheten i prostatacancer med 20 procent i en stor randomiserad studie. En utvärdering av PSA-test med sannolikhetskvot (likelihood ratio) visade att det inte uppfyller kriterierna för ett screeningtest. Män ska ha information om PSA-testets för- och nackdelar innan testet utförs. En broschyr med sådan information finns tillgänglig på <http://www.socialstyrelsen.se/publikationer2007/2007-114-90>.
  • Johansson, Mattias, et al. (författare)
  • One-carbon metabolism and prostate cancer risk : prospective investigation of seven circulating B vitamins and metabolites
  • 2009
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965. ; 18:5, s. 1538-1543
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Components of one-carbon metabolism are believed to influence cancer development with suggested mechanisms, including DNA methylation and DNA repair mechanisms. However, few prospective studies have investigated one-carbon metabolism in relation to prostate cancer risk, and the results have been conflicting. The aim of this study was to do a comprehensive investigation of the components of one-carbon metabolism in relation to prostate cancer risk. A panel of seven circulating B vitamins and related metabolites was selected, most of which have not been studied before. MATERIALS AND METHODS: We analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls matched for age and recruitment date, nested within the population-based Northern Sweden Health and Disease Cohort. Relative risks of prostate cancer were estimated by conditional logistic regression. RESULTS: Positive associations with prostate cancer risk were observed for choline and vitamin B2, and an inverse association was observed for MMA. The relative risks for a doubling in concentrations were 1.46 [95% confidence interval (95% CI), 1.04-2.05; P(trend) = 0.03] for choline, 1.11 (95% CI, 1.00-1.23; P(trend) = 0.04) for vitamin B2, and 0.78 (95% CI, 0.63-0.97; P(trend) = 0.03) for MMA. Concentrations of betaine, cysteine, methionine, and vitamin B6 were not associated with prostate cancer risk. CONCLUSION: The results of this large prospective study suggest that elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer. These novel findings support a role of one-carbon metabolism in prostate cancer etiology and warrant further investigation. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1538-43).
  • Kaaks, Rudolf, et al. (författare)
  • Insulin-like Growth Factor-II Methylation Status in Lymphocyte DNA and Colon Cancer Risk in the Northern Sweden Health and Disease Cohort
  • 2009
  • Ingår i: Cancer Research. - 0008-5472. ; 69:13, s. 5400-5405
  • Tidskriftsartikel (refereegranskat)abstract
    • Loss of imprinting (LOI) of the insulin-like growth factor II (IGFII) gene is a frequent phenomenon in colorectal tumor tissues. Previous reports indicated that subjects with colorectal neoplasias show LOI of IGFII in circulating lymphocytes. Furthermore, LOI of IGFII is strongly related to the methylation of a differentially methylated region (DMR) in intron 2 of IGFII, suggesting that the methylation status could serve as a biomarker for early detection. Thus, hypermethylation of this DMR, even at a systemic level, e.g., in lymphocyte DNA, could be used for screening for colon cancer. To validate this, we performed a case-control study of 97 colon cancer cases and 190 age-matched and gender-matched controls, nested within the prospective Northern Sweden Health and Disease Study cohort. Methylation levels of the IGFII-DMR in lymphocyte DNA were measured at two specific CpG sites of the IGFII-DMR using a mass-spectrometric method called short oligonucleotide mass analysis, the measurements of which showed high reproducibility between replicate measurements for the two CpG sites combined and showed almost perfect validity when performed on variable mixtures of methylated and unmethylated standards. Mean fractions of CpG methylation, for the two CpG sites combined, were identical for cases and controls (0.47 and 0.46, respectively; Pdifference = 0.75), and logistic regression analyses showed no relationship between colon cancer risk and quartile levels of CpG methylation. The results from this study population do not support the hypothesis that colon cancer can be predicted from the different degrees of methylation of DMR in the IGFII gene from lymphocyte DNA. [Cancer Res 2009;69(13):5400-5].
  • Stenman, Katarina, et al. (författare)
  • Detection of polyunsaturated omega-6 fatty acid in human malignant prostate tissue by 1D and 2D high-resolution magic angle spinning NMR spectroscopy
  • 2009
  • Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - Berlin : Springer. - 0968-5243. ; 22:6, s. 327-331
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECT: Polyunsaturated omega-6 fatty acids (PUFAs) have been shown to promote prostate cancer. Here, we describe the use of HRMAS NMR spectroscopy to detect omega-6 PUFA species in prostate tissues. MATERIALS AND METHODS: Samples originating from non-malignant (n = 54) and malignant (n = 27) prostate tissues (from 27 prostatectomized men) were studied by 1D (1)H, 2D (1)H-(1)H and (1)H-(13)C HRMAS NMR spectroscopy followed by histopathological characterization. RESULTS: HRMAS NMR proved to be a powerful, non-destructive method to identify and characterize PUFAs. The omega-6 PUFA was found in 15% of examined human prostate tumors. CONCLUSION: It is possible to detect PUFAs in prostate tissues using our NMR-based spectroscopic approach.
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