| 21. |
- Cust, Anne E, et al.
(författare)
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The influence of overweight and insulin resistance on breast cancer risk and tumour stage at diagnosis : a prospective study.
- 2009
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Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 113:3, s. 567-576
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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.
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| 22. |
- Holmström, Benny, 1974-, et al.
(författare)
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Prostate specific antigen for early detection of prostate cancer : longitudinal study
- 2009
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Ingår i: BMJ (Clinical research ed.). - : BMJ. - 1468-5833 .- 0959-8138. ; 339, s. b3537-
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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.
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| 23. |
- Holmström, Benny, et al.
(författare)
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PSA-testet håller inte för screening: bra – men inte tillräckligt bra : [The PSA test does not hold for screening: good – but not good enough]
- 2009
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Ingår i: Läkartidningen. - : Sveriges läkarförbund. - 0023-7205 .- 1652-7518. ; 107:7, s. 436, 438-439
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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 .
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| 24. |
- Johansson, Mattias, et al.
(författare)
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One-carbon metabolism and prostate cancer risk : prospective investigation of seven circulating B vitamins and metabolites
- 2009
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 18:5, s. 1538-1543
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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).
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| 25. |
- Kaaks, Rudolf, et al.
(författare)
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Insulin-like Growth Factor-II Methylation Status in Lymphocyte DNA and Colon Cancer Risk in the Northern Sweden Health and Disease Cohort
- 2009
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 69:13, s. 5400-5405
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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].
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| 26. |
- Stenman, Katarina, et al.
(författare)
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Detection of polyunsaturated omega-6 fatty acid in human malignant prostate tissue by 1D and 2D high-resolution magic angle spinning NMR spectroscopy
- 2009
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Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - Berlin : Springer. - 0968-5243 .- 1352-8661. ; 22:6, s. 327-331
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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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| 27. |
- Travis, Ruth C, et al.
(författare)
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Serum vitamin D and risk of prostate cancer in a case-control analysis nested within the European Prospective Investigation into Cancer and Nutrition (EPIC).
- 2009
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 169:10, s. 1223-1232
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Tidskriftsartikel (refereegranskat)abstract
- Results from the majority of studies show little association between circulating concentrations of vitamin D and prostate cancer risk, a finding that has not been demonstrated in a wider European population, however. The authors examined whether vitamin D concentrations were associated with prostate cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (1994-2000). Serum concentrations of 25-hydroxyvitamin D were measured in 652 prostate cancer cases matched to 752 controls from 7 European countries after a median follow-up time of 4.1 years. Conditional logistic regression models were used to calculate odds ratios for prostate cancer risk in relation to serum 25-hydroxyvitamin D after standardizing for month of blood collection and adjusting for covariates. No significant association was found between 25-hydroxyvitamin D and risk of prostate cancer (highest vs. lowest quintile: odds ratio = 1.28, 95% confidence interval: 0.88, 1.88; P for trend = 0.188). Subgroup analyses showed no significant heterogeneity by cancer stage or grade, age at diagnosis, body mass index, time from blood collection to diagnosis, or calcium intake. In summary, the results of this large nested case-control study provide no evidence in support of a protective effect of circulating concentrations of vitamin D on the risk of prostate cancer.
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| 28. |
- Wikström, Pernilla, et al.
(författare)
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Low stroma androgen receptor level in normal and tumor prostate tissue is related to poor outcome in prostate cancer patients.
- 2009
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Ingår i: The Prostate. - : Wiley. - 1097-0045 .- 0270-4137. ; 69:8, s. 799-809
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The role of androgen receptors (ARs) in the prostate tumor cell environment is largely unknown. METHODS: AR immunostaining was evaluated in relation to stroma morphology, expression of AR co-activator ARA55, tumor characteristics and clinical outcome in normal and prostate cancer (PCa) tissue obtained at transurethral resection in men treated with expectancy, and in diagnostic transrectal core biopsies in men treated with surgical castration. Stroma composition was studied by Masson-trichrome and desmin staining. Levels of AR and ARA55 mRNA were quantified by laser micro-dissection and RT-PCR. RESULTS: The percentage of cells with positive nuclear AR immunostaining in the tumor and normal stroma was inversely related to Gleason score, tumor size, tumor stage, metastasis, response to castration therapy, and cancer-specific survival. The AR staining in the normal stroma provided independent prognostic information in Cox multiple linear regression analysis. Loss of stroma AR staining was linked to low expression of ARA55 in stroma smooth muscle cells, and in tumors also to gradual disappearance of this cell type. CONCLUSIONS: PCa aggressiveness and efficacy of castration therapy are related to AR levels in the tumor stroma and importantly to AR levels in the surrounding normal prostate tissue stroma. .
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