Liebe Mitstreiter,
in der Public Library of Science (PLoS) homepage ist dieser Abstrakt zur Studie des Vitamin D und Prostatakrebs erschienen. Ich kann den Text aus zeitlichen Gründen nicht übersetzen. Wer Interesse hat, dem kann ich den Langtext zusenden. Ich hoffe damit weitere Information zur Wichtigkeit ausreichender Vit. D Spiegel im Zusammenhang mit Prostatkrebs weitergeben zu können.
Günter
A Prospective Study of Plasma Vitamin D Metabolites, Vitamin D Receptor Polymorphisms, and Prostate Cancer
Haojie Li1*, Meir J. Stampfer1,2,3,4,5, J. Bruce W. Hollis6, Lorelei A. Mucci1, J. Michael Gaziano4,5, David Hunter1,2,3, Edward L. Giovannucci1,2,3, Jing Ma1
1 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America, 3 Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America, 4 Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, 5 Massachusetts Veterans Epidemiology Research and Information Center, Veterans Administration Boston Healthcare System, Massachusetts, United States of America, 6 Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, United States of America
Background Vitamin D insufficiency is a common public health problem nationwide. Circulating 25-hydroxyvitamin D3 (25[OH]D), the most commonly used index of vitamin D status, is converted to the active hormone 1,25 dihydroxyvitamin D3 (1,25[OH]2D), which, operating through the vitamin D receptor (VDR), inhibits in vitro cell proliferation, induces differentiation and apoptosis, and may protect against prostate cancer. Despite intriguing results from laboratory studies, previous epidemiological studies showed inconsistent associations of circulating levels of 25(OH)D, 1,25(OH)2D, and several VDR polymorphisms with prostate cancer risk. Few studies have explored the joint association of circulating vitamin D levels with VDR polymorphisms.
Methods and Findings During 18 y of follow-up of 14,916 men initially free of diagnosed cancer, we identified 1,066 men with incident prostate cancer (including 496 with aggressive disease, defined as stage C or D, Gleason 7–10, metastatic, and fatal prostate cancer) and 1,618 cancer-free, age- and smoking-matched control participants in the Physicians' Health Study. We examined the associations of prediagnostic plasma levels of 25(OH)D and 1,25(OH)2D, individually and jointly, with total and aggressive disease, and explored whether relations between vitamin D metabolites and prostate cancer were modified by the functional VDR FokI polymorphism, using conditional logistic regression. Among these US physicians, the median plasma 25(OH)D levels were 25 ng/ml in the blood samples collected during the winter or spring and 32 ng/ml in samples collected during the summer or fall. Nearly 13% (summer/fall) to 36% (winter/spring) of the control participants were deficient in 25(OH)D (<20 ng/ml) and 51% (summer/fall) and 77% (winter/spring) had insufficient plasma 25(OH)D levels (<32 ng/ml). Plasma levels of 1,25(OH)2D did not vary by season. Men whose levels for both 25(OH)D and 1,25(OH)2D were below (versus above) the median had a significantly increased risk of aggressive prostate cancer (odds ratio [OR] = 2.1, 95% confidence interval [CI] 1.2–3.4), although the interaction between the two vitamin D metabolites was not statistically significant (pinteraction = 0.23). We observed a significant interaction between circulating 25(OH)D levels and the VDR FokI genotype (pinteraction < 0.05). Compared with those with plasma 25(OH)D levels above the median and with the FokI FF or Ff genotype, men who had low 25(OH)D levels and the less functional FokI ff genotype had increased risks of total (OR = 1.9, 95% CI 1.1–3.3) and aggressive prostate cancer (OR = 2.5, 95% CI 1.1–5.8). Among men with plasma 25(OH)D levels above the median, the ff genotype was no longer associated with risk. Conversely, among men with the ff genotype, high plasma 25(OH)D level (above versus below the median) was related to significant 60%
70% lower risks of total and aggressive prostate cancer.
Conclusions Our data suggest that a large proportion of the US men had suboptimal vitamin D status (especially during the winter/spring season), and both 25(OH)D and 1,25(OH)2D may play an important role in preventing prostate cancer progression. Moreover, vitamin D status, measured by 25(OH)D in plasma, interacts with the VDR FokI polymorphism and modifies prostate cancer risk. Men with the less functional FokI ff genotype (14% in the European-descent population of this cohort) are more susceptible to this cancer in the presence of low 25(OH)D status.
Funding: Supported in part by grants from the National Institutes of Health (CA-42182 and CA-58684) and the U.S. Army Medical Research (PC030095). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
in der Public Library of Science (PLoS) homepage ist dieser Abstrakt zur Studie des Vitamin D und Prostatakrebs erschienen. Ich kann den Text aus zeitlichen Gründen nicht übersetzen. Wer Interesse hat, dem kann ich den Langtext zusenden. Ich hoffe damit weitere Information zur Wichtigkeit ausreichender Vit. D Spiegel im Zusammenhang mit Prostatkrebs weitergeben zu können.
Günter
A Prospective Study of Plasma Vitamin D Metabolites, Vitamin D Receptor Polymorphisms, and Prostate Cancer
Haojie Li1*, Meir J. Stampfer1,2,3,4,5, J. Bruce W. Hollis6, Lorelei A. Mucci1, J. Michael Gaziano4,5, David Hunter1,2,3, Edward L. Giovannucci1,2,3, Jing Ma1
1 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America, 3 Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America, 4 Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, 5 Massachusetts Veterans Epidemiology Research and Information Center, Veterans Administration Boston Healthcare System, Massachusetts, United States of America, 6 Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, United States of America
Background Vitamin D insufficiency is a common public health problem nationwide. Circulating 25-hydroxyvitamin D3 (25[OH]D), the most commonly used index of vitamin D status, is converted to the active hormone 1,25 dihydroxyvitamin D3 (1,25[OH]2D), which, operating through the vitamin D receptor (VDR), inhibits in vitro cell proliferation, induces differentiation and apoptosis, and may protect against prostate cancer. Despite intriguing results from laboratory studies, previous epidemiological studies showed inconsistent associations of circulating levels of 25(OH)D, 1,25(OH)2D, and several VDR polymorphisms with prostate cancer risk. Few studies have explored the joint association of circulating vitamin D levels with VDR polymorphisms.
Methods and Findings During 18 y of follow-up of 14,916 men initially free of diagnosed cancer, we identified 1,066 men with incident prostate cancer (including 496 with aggressive disease, defined as stage C or D, Gleason 7–10, metastatic, and fatal prostate cancer) and 1,618 cancer-free, age- and smoking-matched control participants in the Physicians' Health Study. We examined the associations of prediagnostic plasma levels of 25(OH)D and 1,25(OH)2D, individually and jointly, with total and aggressive disease, and explored whether relations between vitamin D metabolites and prostate cancer were modified by the functional VDR FokI polymorphism, using conditional logistic regression. Among these US physicians, the median plasma 25(OH)D levels were 25 ng/ml in the blood samples collected during the winter or spring and 32 ng/ml in samples collected during the summer or fall. Nearly 13% (summer/fall) to 36% (winter/spring) of the control participants were deficient in 25(OH)D (<20 ng/ml) and 51% (summer/fall) and 77% (winter/spring) had insufficient plasma 25(OH)D levels (<32 ng/ml). Plasma levels of 1,25(OH)2D did not vary by season. Men whose levels for both 25(OH)D and 1,25(OH)2D were below (versus above) the median had a significantly increased risk of aggressive prostate cancer (odds ratio [OR] = 2.1, 95% confidence interval [CI] 1.2–3.4), although the interaction between the two vitamin D metabolites was not statistically significant (pinteraction = 0.23). We observed a significant interaction between circulating 25(OH)D levels and the VDR FokI genotype (pinteraction < 0.05). Compared with those with plasma 25(OH)D levels above the median and with the FokI FF or Ff genotype, men who had low 25(OH)D levels and the less functional FokI ff genotype had increased risks of total (OR = 1.9, 95% CI 1.1–3.3) and aggressive prostate cancer (OR = 2.5, 95% CI 1.1–5.8). Among men with plasma 25(OH)D levels above the median, the ff genotype was no longer associated with risk. Conversely, among men with the ff genotype, high plasma 25(OH)D level (above versus below the median) was related to significant 60%
70% lower risks of total and aggressive prostate cancer.Conclusions Our data suggest that a large proportion of the US men had suboptimal vitamin D status (especially during the winter/spring season), and both 25(OH)D and 1,25(OH)2D may play an important role in preventing prostate cancer progression. Moreover, vitamin D status, measured by 25(OH)D in plasma, interacts with the VDR FokI polymorphism and modifies prostate cancer risk. Men with the less functional FokI ff genotype (14% in the European-descent population of this cohort) are more susceptible to this cancer in the presence of low 25(OH)D status.
Funding: Supported in part by grants from the National Institutes of Health (CA-42182 and CA-58684) and the U.S. Army Medical Research (PC030095). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.