| 1. |
- Johansson, Mattias, et al.
(författare)
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Combining 33 genetic variants with prostate-specific antigen for prediction of prostate cancer : longitudinal study
- 2012
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 130:1, s. 129-137
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate if a genetic risk score including 33 common genetic variants improves prediction of prostate cancer when added to measures of prostate-specific antigen (PSA). We conducted a case-control study nested within the Northern Sweden Health and Disease Cohort (NSHDC), a prospective cohort in northern Sweden. A total of 520 cases and 988 controls matched for age, and date of blood draw were identified by linkage between the regional cancer register and the NSHDC. Receiver operating characteristic curves with area under curve (AUC) estimates were used as measures of prostate cancer prediction. The AUC for the genetic risk score was 64.3% [95% confidence interval (CI) = 61.4-67.2], and the AUC for total PSA and the ratio of free to total PSA was 86.2% (95% CI = 84.4-88.1). A model including the genetic risk score, total PSA and the ratio of free to total PSA increased the AUC to 87.2% (95% CI = 85.4-89.0, p difference = 0.002). The addition of a genetic risk score to PSA resulted in a marginal improvement in prostate cancer prediction that would not seem useful for clinical risk assessment.
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| 2. |
- Johansson, Mattias, et al.
(författare)
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Genetic variation in the SST gene and its receptors in relation to circulating levels of insulin-like growth factor-I, IGFBP3, and prostate cancer risk
- 2009
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : AMER ASSOC CANCER RESEARCH. - 1055-9965 .- 1538-7755. ; 18:5, s. 1644-1650
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Somatostatin (SST) and its receptors (SSTR1-5) may have a role in prostate cancer by influencing the IGFI hormone axis or through direct effects on prostate epithelia. We have investigated if genetic variation in the SST and SSTR1-5 genes influences prostate cancer risk and/or circulating IGFI and IGFBP3 hormone levels. MATERIALS AND METHODS: We analyzed 28 haplotype tagging single nucleotide polymorphisms in the SST and SSTR1-5 genes in a case-control/genetic association study to investigate the association between genetic variation and prostate cancer risk. The study included 2863 cases and 1737 controls from the Cancer Prostate in Sweden (CAPS) study. To investigate the genetic influence on circulating hormone levels, plasma concentrations of IGFI and IGFBP3 were analyzed in 874 controls of the CAPS study and 550 male subjects from the Northern Sweden Health and Disease Cohort (NSHDC). RESULTS: No clear association between prostate cancer risk and genetic variation of the SST and SSTR1-5 genes was identified. The SSTR5 missense single nucleotide polymorphism rs4988483 was associated with circulating IGFI (P = 0.002) and IGFBP3 (P = 0.0003) hormone levels in CAPS controls, with a per allele decrease of approximately 11%. This decrease was replicated in NSHDC for circulating IGFBP3 (P = 0.01) but not for IGFI (P = 0.09). Combining CAPS and NSHDC subjects indicated evidence of association between rs4988483 and both IGFBP3 (P = 2 x 10(-5)) and IGFI (P = 0.0004) hormone levels. CONCLUSIONS: Our results suggest that genetic variation in the SSTR5 gene and, particularly, the rs4988483 single nucleotide polymorphism influence circulating IGFI and IGFBP3 hormone levels with no measurable effect on prostate cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1644-50).
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| 3. |
- Toss, Fredrik, 1984-, et al.
(författare)
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Abdominal and gynoid adiposity and the risk of stroke
- 2011
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 35:11, s. 1427-1432
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have indicated that fat distribution is important in the development of cardiovascular disease (CVD). We investigated the association between fat distribution, as measured by dual energy X-ray absorptiometry (DXA), and the incidence of stroke. Methods: A cohort of 2751 men and women aged >= 40 years was recruited. Baseline levels of abdominal, gynoid and total body fat were measured by DXA. Body mass index (BMI, kg m(-2)) was calculated. Stroke incidence was recorded using the regional stroke registry until subjects reached 75 years of age. Results: During a mean follow-up time of 8 years and 9 months, 91 strokes occurred. Of the adiposity indices accessed abdominal fat mass was the best predictor of stroke in women (hazard ratio (HR) = 1.66, 95% confidence interval (CI) = 1.23-2.24 per standard deviation increase), whereas the ratio of gynoid fat to total fat mass was associated with a decreased risk of stroke (HR = 0.72, 95% CI = 0.54-0.96). Abdominal fat mass was the only of the adiposity indices assessed that was found to be a significant predictor of stroke in men (HR = 1.49, 95% CI = 1.06-2.09). The associations between abdominal fat mass and stroke remained significant in both women and men after adjustment for BMI (HR = 1.80, 95% CI = 1.06-3.07; HR = 1.71, 95% CI = 1.13-2.59, respectively). However, in a subgroup analyses abdominal fat was not a significant predictor after further adjustment for diabetes, smoking and hypertension. Conclusion: Abdominal fat mass is a risk factor for stroke independent of BMI, but not independent of diabetes, smoking and hypertension. This indicates that the excess in stroke risk associated with abdominal fat mass is at least partially mediated through traditional stroke risk factors. International Journal of Obesity (2011) 35, 1427-1432; doi: 10.1038/ijo.2011.9; published online 22 February 2011
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| 4. |
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| 5. |
- Wiklund, Peder, et al.
(författare)
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Abdominal and gynoid adipose distribution and incident myocardial infarction in women and men
- 2010
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 34:12, s. 1752-1758
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Tidskriftsartikel (refereegranskat)abstract
- In summary, fat distribution was a strong predictor of the risk of MI in women, but not in men. These different results may be explained by the associations found between fat distribution and hypertension, impaired glucose tolerance and hypertriglyceridemia.
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| 6. |
- Wiklund, Peder, et al.
(författare)
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Abdominal and gynoid fat mass are associated with cardiovascular risk factors in men and women
- 2008
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:11, s. 4360-4366
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Abdominal obesity is an established risk factor for cardiovascular disease (CVD). However, the correlation of dual-energy x-ray absorptiometry (DEXA) measurements of regional fat mass with CVD risk factors has not been completely investigated. OBJECTIVE: The aim of this study was to investigate the association of estimated regional fat mass, measured with DEXA and CVD risk factors. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study of 175 men and 417 women. DEXA measurements of regional fat mass were performed on all subjects, who subsequently participated in a community intervention program. MAIN OUTCOME MEASURES: Outcome measures included impaired glucose tolerance, hypercholesterolemia, hypertriglyceridemia, and hypertension. RESULTS: We began by assessing the associations of the adipose measures with the cardiovascular outcomes. After adjustment for confounders, a sd unit increase in abdominal fat mass was the strongest predictor of most cardiovascular variables in men [odds ratio (OR)=2.63-3.37; P<0.05], whereas the ratio of abdominal to gynoid fat mass was the strongest predictor in women (OR=1.48-2.19; P<0.05). Gynoid fat mass was positively associated with impaired glucose tolerance, hypertriglyceridemia, and hypertension in men (OR=2.07-2.15; P<0.05), whereas the ratio of gynoid to total fat mass showed a negative association with hypertriglyceridemia and hypertension (OR=0.42-0.62; P<0.005). CONCLUSIONS: Abdominal fat mass is strongly independently associated with CVD risk factors in the present study. In contrast, gynoid fat mass was positively associated, whereas the ratio of gynoid to total fat mass was negatively associated with risk factors for CVD.
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