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- Couch, Fergus J., et al.
(författare)
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AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A consortium of investigators of modifiers of BRCA1/2 study
- 2007
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 16:7, s. 1416-1421
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Tidskriftsartikel (refereegranskat)abstract
- The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 311 allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.061. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% Cl, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers.
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- Spaak, J, et al.
(författare)
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Dose-related effects of red wine and alcohol on hemodynamics, sympathetic nerve activity, and arterial diameter
- 2008
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Ingår i: American journal of physiology. Heart and circulatory physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 294:2, s. H605-H612
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Tidskriftsartikel (refereegranskat)abstract
- The cardiovascular benefits of light to moderate red wine consumption often have been attributed to its polyphenol constituents. However, the acute dose-related hemodynamic, vasodilator, and sympathetic neural effects of ethanol and red wine have not been characterized and compared in the same individual. We sought to test the hypotheses that responses to one and two alcoholic drinks differ and that red wine with high polyphenol content elicits a greater effect than ethanol alone. Thirteen volunteers (24–47 yr; 7 men, 6 women) drank wine, ethanol, and water in a randomized, single-blind trial on three occasions 2 wk apart. One drink of wine and ethanol increased blood alcohol to 38 ± 2 and 39 ± 2 mg/dl, respectively, and two drinks to 72 ± 4 and 83 ± 3 mg/dl, respectively. Wine quadrupled plasma resveratrol ( P < 0.001) and increased catechin ( P < 0.03). No intervention affected blood pressure. One drink had no heart rate effect, but two drinks of wine increased heart rate by 5.7 ± 1.6 beats/min; P < 0.001). Cardiac output fell 0.8 ± 0.3 l/min after one drink of ethanol and wine (both P < 0.02) but increased after two drinks of ethanol (+0.8 ± 0.3 l/min) and wine (+1.2 ± 0.3 l/min) ( P < 0.01). One alcoholic drink did not alter muscle sympathetic nerve activity (MSNA), while two drinks increased MSNA by 9–10 bursts/min ( P < 0.001). Brachial artery diameter increased after both one and two alcoholic drinks ( P < 0.001). No beverage augmented, and the second wine dose attenuated ( P = 0.02), flow-mediated vasodilation. One drink of ethanol dilates the brachial artery without activating sympathetic outflow, whereas two drinks increase MSNA, heart rate, and cardiac output. These acute effects, which exhibit a narrow dose response, are not modified by red wine polyphenols.
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