12 juni 2005: Bron: Clinical Care Options

Wanneer mannen ouder dan 60 een hoge waarde van vitamine D. - 1,25D en 25D - in hun bloed hebben dan helpt dat significant ter bescherming van het eventueel ontwikkelen van bepaalde agressieve vormen van prostaatkanker. Wanneer die vitamine D. waarden lager zijn dan loopt het risico op prostaatkanker snel op tot het dubbele risico bij laagste waarden t.o.v. gemiddelde waarden, vooral voor mannen boven de 60 jaar. Op ASCO 2005 werd een gerandomiseerde studie met een followup van 18 jaar daarmee gepresenteerd , maar even snel zoeken in Pubmed levert meerdere studies op die allemaal ditzelfde beeld bevestigen. Het lijkt dan ook raadzaam voor mannen boven de zeg 50 jaar om aanvullend die bepaalde vitamine D. waarden aan te vullen met suppletie en/of veel in de zon te zijn. Zonlicht maakt namelijk vitamine D. aan. Ook goed ter bescherming voor andere kankersoorten overigens. Maar voor extra suppletie - vitamine E. en lycopeen bv. lijken ook beschermend tegen krijgen van prostaatkanker - ga naar een goed gekwalificeerde orthomoleculaire arts die weten hier normaal gesproken alles vanaf. Hier wat gekopieerde gegevens uit de studie zoals die op ASCO 2005 werd gepresenteerd gevolgd door meerdere abstracten met zelfde onderzoeksgegevens en resultaten.

Hier in het Nederlands de belangrijkste conclusies uit de meest recente studie van ASCO 2005, zo goed als letterlijk vertaald.

Hoofdconclusies: Mannen met lagere gemiddelde waarden van beide soorten vitamine D. nl. 1,25D en 25D hadden een twee keer zo groot risico op het ontwikkelen van aggressieve prostaatkanker gedurende 18-jaar follow-up Relatieve risico (RR) = 1.8, 95% confidence interval (CI), 1.1-3.0 Een klein maar significant groter risico voor alle vormen van prostaatkanker werd vastgesteld: RR voor laag- versus boven-gemiddelde 1,25D + 25D waarden = 1.2; 95% CI, 0.9-1.7 Individueel, basiswaarden van 1,25D en 25D beinvloedde niet het risico op prostaatkanker. Laagste versus hoogste waardemeting van vitamine 1,25D: RR = 1.0; 95% CI, 0.7-1.5 P voor trend tussen de meetwaarden = .85 Laagste versus hoogste meetwaarde van vitamine 25D : RR = 1.0; 95% CI, 0.7-1.4 P voor trend tussen de meetwaarden = .90 Alleen FokI en BsmIvitamine D receptor genotype had geen significante invloed op prostaat kanker risico.

Significante interactie tussen FokI genotype en gecombineerd vitamine D waarden in relatie tot prostaat kanker risico : voor mannen met FokI FF genotype: Verhoogd risico voor prostaat kanker met lage 1,25D en 25D (RR = 2.2; 95% CI, 1.0-4.7; P voor interactiie = .01) Verhoogd risico voor agressieve ziekte met lage vitamine D. waarden: (RR = 3.8; 95% CI, 1.3-11.2; P voor interactie = .03) Geen interactie tussen BsmI genotype en vitamine D waarden voor prostaat kanker risico Higher Vitamin D Levels Protective Against Aggressive Prostate Cancer, Especially in Men With Receptor Polymorphism

Summary of Key Conclusions Men with above-median vitamin D levels less like to develop prostate cancer High vitamin D levels appear to protect against aggressive disease Benefit observed only when levels of both 1,25-dihydroxyvitamin D (1,25D) and 25-hydroxyvitamin D (25D) are elevated Men with receptor FokI FF genotype are more sensitive to circulating to vitamin D Vitamin D obtained from exposure to sunlight and from dietary sources an important part of maintaining prostate health Background Biological functions of vitamin D may protect against prostate cancer initiation and progression by: Reducing cellular proliferation and/or angiogenesis Increasing cellular differentiation and/or apoptosis Vitamin D receptors in the prostate mediate activity of 1,25D Receptor polymorphisms may alter vitamin D activity FokI F vs f polymorphism associated with Increased sensitivity to vitamin D Increased interaction with transcriptional factors BsmI Current study investigated the effect of vitamin D on prostate cancer risk in men who were cancer-free at enrollment and diagnosed with prostate cancer during 18 years of follow-up Impact of vitamin D receptor polymorphisms also investigated Summary of Study Design Nested case-control analysis of Physicians' Health Study cohort (n = 22,071) Only participants deemed healthy were enrolled Blood samples available from 14,916 men at time of enrollment in 1982 Men who developed prostate cancer by 2000 evaluated in current analysis (n = 1082) Age-matched controls selected for comparison (n = 1471) Biochemical analysis of stored blood samples Vitamin D levels 1,25D 25D Genotyping for vitamin D receptor polymorphisms FokI BsmI Prostate cancer evaluation Cancer stage Gleason scoring Aggressive disease defined as Stage C or D cancer, or Gleason score of 7-10, or Prostate cancer fatality Statistics Conditional logistic regression Used to examine whether associations between prostate cancer and vitamin D metabolites varied according to vitamin D receptor genotype Main Findings Men with below-median levels of both 1,25D and 25D at baseline had 2-fold increased risk for developing aggressive prostate cancer during 18-years follow-up Relative risk (RR) = 1.8, 95% confidence interval (CI), 1.1-3.0 A small but significantly greater risk of all-type prostate cancer was observed RR for below- vs above-median 1,25D + 25D levels = 1.2; 95% CI, 0.9-1.7 Individually, baseline levels of 1,25D and 25D did not influence prostate cancer risk Lowest vs highest quintile of vitamin 1,25D RR = 1.0; 95% CI, 0.7-1.5 P for trend across quintiles = .85 Lowest vs highest quintile of vitamin 25D RR = 1.0; 95% CI, 0.7-1.4 P for trend across quintiles = .90 Alone, FokI and BsmIvitamin D receptor genotype had no significant influence on prostate cancer risk Significant interaction between FokI genotype and combined vitamin D levels with respect to prostate cancer risk For men with FokI FF genotype Increased risk for prostate cancer with low 1,25D and 25D (RR = 2.2; 95% CI, 1.0-4.7; P for interaction = .01) Increased risk for aggressive disease with low vitamin D levels (RR = 3.8; 95% CI, 1.3-11.2; P for interaction = .03) No interaction between BsmI genotype and vitamin D levels for prostate cancer risk Reference Li H, Stamfer E, Giovannucci E, et al. Prediagnostic plasma vitamin D levels, vitamin D receptor gene polymorphisms, and susceptibility to prostate cancer. Program and abstracts of the 2005 Multidisciplinary Prostate Cancer Symposium; February 17-20; Orlando, Florida. Abstract 2. Al in 1998 publiceerden dezelfde onderzoekers al een gerandomiseerde studie die aangeeft dat een bepaald niveau van bepaalde soort vitamine D. in het bloed bij oudere mannen een beschermende rol speelt in het risico op het krijgen van prostaatkanker. Hier het abstract van deze dubbelblinde gerandomiseerde studie

Cancer Epidemiol Biomarkers Prev. 1998 May;7(5):385-90.

Vitamin D receptor polymorphisms, circulating vitamin D metabolites, and risk of prostate cancer in United States physicians.

Ma J, Stampfer MJ, Gann PH, Hough HL, Giovannucci E, Kelsey KT, Hennekens CH, Hunter DJ.
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

Prostatic cells express vitamin D receptor (VDR), which mediates the functions of 1,25-dihydroxyvitamin D. Two recent case-control studies suggested strong inverse associations between two VDR polymorphisms, TaqI and poly(A), and risk of prostate cancer. These two and a third polymorphism, BsmI, are closely linked. In a case-control study nested in the Physicians' Health Study, a randomized double-blind trial of aspirin and beta-carotene among 22,071 United States male physicians, we examined the associations between BsmI and TaqI and prostate cancer risk and whether the associations varied according to age and vitamin D metabolite levels among 372 incident cases and 591 controls. Among controls, the BB genotype was significantly associated with higher 1,25-dihydroxyvitamin D (median = 36.2 pg/ml for the BB versus 33.9 pg/ml for the bb genotype; P = 0.02), suggesting an association of the VDR polymorphisms with VDR function. Overall, we observed no significant associations of these VDR polymorphisms with prostate cancer risk: relative risk (RR) = 0.86 [95% confidence interval (CI) = 0.57-1.29] for the BB genotype and RR = 0.92 (95% CI = 0.69-1.22) for the Bb genotype, compared with the bb genotype (results were similar for the TaqI polymorphism). Stratification by age (< or = 61 and > 61 years) and tumor aggressiveness showed no significant associations. However, in an analysis restricted to men with plasma 25-hydroxyvitamin D below the median, we observed a 57% reduction (RR = 0.43, 95% CI = 0.19-0.98) in risk for those with the BB versus the bb genotype; the risk reduction was particularly marked among older men (RR = 0.18, 95% CI = 0.05-0.68). We did not observe this inverse association among men with 25-hydroxyvitamin D levels above the median, nor did we observe it among younger men.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 9610787 [PubMed - indexed for MEDLINE]

Hier nog enkele abstracten van studies verwant aan bovenstaande studies:

Cancer Res. 2000 Jan 15;60(2):305-8.

Association of vitamin D receptor gene polymorphism with prostate cancer and benign prostatic hyperplasia in a Japanese population.

Habuchi T, Suzuki T, Sasaki R, Wang L, Sato K, Satoh S, Akao T, Tsuchiya N, Shimoda N, Wada Y, Koizumi A, Chihara J, Ogawa O, Kato T.
Department of Urology, Akita University School of Medicine, Japan.

Recent studies have suggested that vitamin D is an important determinant of prostate cancer risk and inherited polymorphisms in the 3'-untranslated region (3'UTR) of the vitamin D receptor (VDR) gene are associated with the risk and progression of prostate cancer. This study was conducted to explore the association of VDR gene polymorphisms with prostate cancer risk in Japanese men who are considered to be much less influenced by environmental risk factors for prostate cancer. We studied 222 prostate cancer patients, 209 benign prostatic hyperplasia (BPH) patients, 128 male controls who were over 60 years old and without any evidence of prostate cancer or BPH, and 198 female controls. A PCR-RFLP method was used to determine three VDR gene polymorphisms in the 3'UTR characterized by restriction enzymes BsmI, ApaI and TaqI. In the BsmI polymorphism, heterozygosity or homozygosity for the absence of the BsmI restriction site was associated with one-third the risk of prostate cancer (P < 0.0001; odds ratio, 3.31; 95% confidence interval, 2.05-5.32) and with one-half the risk of BPH (P < 0.005; odds ratio, 2.07; 95% confidence interval, 1.33-3.22) compared with the male controls. The TaqI and ApaI polymorphisms did not show any significant association with either prostate cancer or BPH. The results indicate that the BsmI polymorphism in the VDR gene plays a significant role in protection against prostate cancer and BPH. Because of the racial difference in the strength of the linkage disequilibrium between the three polymorphisms, additional studies are required to apply the present results to other racial-ethnic groups.

PMID: 10667581 [PubMed - indexed for MEDLINE]

Een andere verwante studie:
,br> Cancer Res. 2000 Oct 15;60(20):5710-3.

Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect.

Habuchi T, Liqing Z, Suzuki T, Sasaki R, Tsuchiya N, Tachiki H, Shimoda N, Satoh S, Sato K, Kakehi Y, Kamoto T, Ogawa O, Kato T.
Department of Urology, Akita University School of Medicine, Japan.

The CYP17 gene (CYP17) codes for the cytochrome P450c17alpha enzyme, which mediates two key steps in the sex steroid synthesis. There is a polymorphism (a T-to-C substitution) in the 5'-untranslated region, which may influence the transcription level of CYP17 mRNA. There is a continuing controversy as to whether the variant allele is associated with a subset of breast cancer or polycystic ovary syndrome. In prostate cancer research, there are contradictory data concerning the CYP17 risk allele. We explored the association between CYP17 polymorphism and a risk of prostate cancer or benign prostatic hyperplasia (BPH) in a Japanese population. This study included 252 prostate cancer patients, 202 BPH patients, and 131 male controls. A 451-bp fragment encompassing the polymorphic site was amplified by PCR, treated with restriction enzyme MspA1, and electrophoresed on an agarose gel. The MspA1-undigested allele with the published sequence and the MspA1-digested variant allele were designated as A1 and A2, respectively. There was a significant difference (P < 0.05) in the genotypes between prostate cancer patients and male controls, and between BPH patients and male controls. Men with the A1/A1 CYP17 genotype had an increased risk of prostate cancer [odds ratio (OR), 2.57; 95% confidence interval (CI) = 1.39-4.78] and BPH (OR, 2.44; 95% CI = 1.26-4.72) compared with those with the A2/A2 genotype. Men with the A1/A2 genotype had an intermediate increased risk of prostate cancer (OR, 1.45; 95% CI = 0.84-2.54) and BPH (OR, 1.60; 95% CI = 0.89-2.87) compared with those with the A2/A2 genotype. The trend of an increasing risk of prostate cancer and BPH with an increasing number of the A1 allele was statistically significant (prostate cancer versus male control, P = 0.003; OR, 1.57; 95% CI = 1.16-2.12; BPH versus male control, P = 0.008; OR, 1.55; 95% CI = 1.12-2.13). There was no significant association between the CYP17 genotype and the tumor status (grade and stage) of prostate cancer. Our results suggest that the A1 allele of the CYP17 polymorphism is associated with an increased risk of prostate cancer and BPH, with a gene dosage effect. However, the CYP17 genotype does not seem to influence the disease status in prostate cancer.

PMID: 11059764 [PubMed - indexed for MEDLINE]

Urol Int. 2002;68(4):226-31.

Significance of vitamin D receptor gene polymorphism for risk and disease severity of prostate cancer and benign prostatic hyperplasia in Japanese.

Hamasaki T, Inatomi H, Katoh T, Ikuyama T, Matsumoto T.
Department of of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan. t-hama@med.uoeh-u.ac.jp

OBJECTIVE: Recent studies have demonstrated an association between vitamin D receptor (VDR) genotype and prostate cancer. Currently, there is a scarcity of data regarding the association of VDR genotype with benign prostatic hyperplasia (BPH). The purpose of this study was to investigate the TaqI VDR polymorphism in Japanese prostate cancer patients, Japanese BPH patients and Japanese controls in order to determine if an association exists between VDR genotype and the risk of developing prostate cancer and BPH as well as disease severity.

METHODS: 110 prostate cancer patients, 83 BPH patients and 90 male age-matched controls were genotyped for a previously described TaqI restriction fragment length polymorphism at codon 352 in exon 9 of the VDR gene. Products were digested into T allele or t allele according to the absence or presence of a TaqI restriction site with individuals being classified as TT, Tt or tt. RESULTS: The frequency of the genotype tt was higher in the control group (6.7%) compared to patients with prostate cancer (1.8%) and BPH (3.6%) but this was not statistically significant. However, the frequency of the genotype TT was significantly higher among prostate cancer patients with locally advanced or metastatic disease (T3/ T4/N1/M1) compared to controls (p = 0.001). In addition, the genotype TT was significantly higher among prostate cancer patients with a high Gleason grade of tumor (grade 5) compared to controls (p = 0.0001). In addition, the genotype TT was statistically higher in BPH patients with high prostate volume (volume >50 cm(3)) compared to controls (p = 0.001). CONCLUSION: These data demonstrate that VDR genotype plays an important role in determining the risk of more advanced and aggressive prostate cancer as well as prostatic enlargement in Japanese men. Copyright 2002 S. Karger AG, Basel

PMID: 12053022 [PubMed - indexed for MEDLINE]


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