Prediagnostic Serum Vitamin D and Breast Cancer

Hiatt, Robert A.; Krieger, Nancy; Lobaugh, Bruce; Drezner, Marc K.; Vogelman, Joseph H.; Orentreich, Norman

doi:10.1093/jnci/90.6.461

Cited by 65 publications

(47 citation statements)

References 20 publications

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“…So far the relationship between vitamin D metabolites and breast cancer has been assessed in studies including postmenopausal or predominantly postmenopausal women without adequate statistical power to address differences by menopausal status. [21][22][23][24][25]33 The largest cohort to date nested in the prostate, lung, colorectal and breast cancer screening trial assessing postmenopausal breast cancer and vitamin D metabolites reported no association. 22 In the NHS stratification by menopausal status did not suggest an inverse association in premenopausal women but power was low in their analyses and neither subgroup specific risk estimates nor p-values of test for statistical interaction were presented.…”

Section: Discussionmentioning

confidence: 99%

Plasma 25‐hydroxyvitamin D and premenopausal breast cancer risk in a German case‐control study

Abbas

Chang‐Claude

Linseisen

2008

Intl Journal of Cancer

110

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Laboratory and epidemiological data have linked vitamin D to breast cancer prevention. Beside dietary intake, endogenous production of vitamin D substantially contributes to a subject's vitamin D status. Most studies, however, have assessed dietary intake only. Although differential effects of vitamin D on premenopausal and postmenopausal breast cancer have been discussed, this is the first study to investigate the association of plasma 25-hydroxyvitamin D [25(OH)D], as indicator of the overall vitamin D status, with breast cancer risk with restriction to premenopausal women only. We used data of a population-based case-control study comprising 289 cases and 595 matched controls. Information on sociodemographic and breast cancer risk factors was collected by questionnaire and plasma 25(OH)D was measured by enzyme immunoassay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. We observed a significant inverse association between breast cancer risk and plasma 25(OH)D concentrations. Compared with the lowest category (<30 nmol/L), the ORs (95% CI) for the upper categories [18][19][20] Few studies have assessed the relationship between serum or plasma 25(OH)D and breast cancer risk. [21][22][23][24][25] Of 2 small hospitalbased case-control studies in predominantly postmenopausal women, one study found a significantly inverse association 23 whereas the other study revealed no association between plasma 25(OH)D and breast cancer risk. 25 To date, 2 studies assessed the association of vitamin D metabolites with breast cancer risk with restriction to postmenopausal women only. 21,22 A study nested in the prostate, lung, colorectal and ovarian cancer screening trial reported no association between both higher plasma 25(OH)D and 1,25(OH) 2 D concentration and breast cancer risk. 22 However, a strong statistically significant inverse association between postmenopausal breast cancer risk and serum 25(OH)D was found in a large case-control study. 21 A case-control study nested in the Nurses' Health Study (NHS) is the only study that so far reported results stratified by menopausal status. 24 The authors reported a nonsignificant decrease in breast cancer risk with both higher plasma 25(OH)D and 1,25(OH) 2 D concentration for overall breast cancer risk. Stratification by menopausal status suggested an inverse association for postmenopausal women only, however power was low for their analysis in premenopausal women and risk estimates were not presented. As reviewed recently, prospective studies on dietary intake of vitamin D suggest a more pronounced effect for premenopausal breast cancer risk. 26 Furthermore, we recently reported a significant inverse association of dietary vitamin D with premenopausal breast cancer risk in the present study population. 13 To our knowledge, no study so far assessed the association of plasma 25(OH)D with restriction to premenopausal breast cancer only. Following our previous report on the association between postmenopausal breast canc...

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Section: Discussionmentioning

confidence: 99%

Plasma 25‐hydroxyvitamin D and premenopausal breast cancer risk in a German case‐control study

Abbas

Chang‐Claude

Linseisen

2008

Intl Journal of Cancer

110

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“…Parallel studies by ourselves and others have found epidemiologic links between the incidence of breast cancers and low serum 25(OH)D 3 levels (13,14); the risk is compounded by specific VDR polymorphisms (15,16). In vitro studies show that MDA-MB-231 and other cancer cells show a spectrum of insensitivity toward 1a,25(OH) 2 D 3 (17, 18).…”

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confidence: 87%

Altered Nuclear Receptor Corepressor Expression Attenuates Vitamin D Receptor Signaling in Breast Cancer Cells

Banwell¹,

MacCartney²,

Guy

et al. 2006

Clinical Cancer Research

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Purpose:We hypothesized that deregulated corepressor actions, with associated histone deacetylation activity, epigenetically suppressed vitamin D receptor (VDR) responsiveness and drives resistance towards 1a,25-dihydroxyvitamin D 3 . Experimental Design: Profiling, transcriptional, and proliferation assays were undertaken in 1a,25(OH) 2 D 3 -sensitive MCF-12A nonmalignant breast epithelial cells, a panel of breast cancer cell lines, and a cohort of primary breast cancer tumors (n = 21). Results: Elevated NCoR1 mRNA levels correlated with suppressed regulation of VDR target genes and the ability of cells to undergo arrest in G 1 of the cell cycle. A similar increased ratio of corepressor mRNA to VDR occurred in matched primary tumor and normal cells, noticeably in estrogen receptor a^negative (n = 7) tumors. 1a,25(OH) 2 D 3 resistance in cancer cell lines was targeted by cotreatments with either 1a,25(OH) 2 D 3 or a metabolically stable analogue (RO-26-2198) in combination with either trichostatin A (TSA; histone deacetylation inhibitor) or 5-aza-2V-deoxycytidine (DNA methyltransferase inhibitor). Combinations of vitamin D 3 compounds with TSA restored VDR antiproliferative signaling (target gene regulation, cell cycle arrest, and antiproliferative effects in liquid culture) to levels which were indistinguishable from MCF-12A cells. Conclusions: Increased NCoR1 mRNA is a novel molecular lesion in breast cancer cells, which acts to suppress responsiveness of VDR target genes, resulting in 1a,25(OH) 2 D 3 resistance and seems to be particularly associated with estrogen receptor negativity.This lesion provides a novel molecular diagnostic and can be targeted by combinations of vitamin D 3 compounds and low doses of TSA.The nuclear receptor superfamily regulates diverse signals that are central to the formation and homeostasis of the mammary gland. The postgenomic description of the superfamily conjoined with profiling approaches (1) reveals that breast myoepithelial and epithelial cells express a rich cohort of nuclear receptors, many of which display overt nutrient-sensing capacity for micronutrients and macronutrients alongside the estrogen receptors (ERa and ERh; refs. 2 -6).Several of the diet-sensing nuclear receptors, such as the VDR, preferentially form heterodimers with retinoid X receptors whereas the ERs preferentially heterodimerize with one another. For the nuclear receptors to regulate transcriptional programs, these dimers must be contained as subunits in either large gene coactivator or corepressor complexes. In the absence of ligand, receptors exist in an apo state as part of large complexes (f2.0 MDa; ref. 7), associated with corepressors (e.g., NCoR1, NCoR2/SMRT, and TRIP15/Alien), and bound to response element sequences. These complexes actively recruit a range of enzymes that posttranslationally modify histone tails (e.g., histone deacetylases and methyltransferases) and thereby maintain a locally closed chromatin structure around response element sequences (8). Ligand binding induces a...

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“…To our knowledge, only two studies have examined the association between circulating vitamin D metabolites and subsequent breast cancer risk. One small study (n = 96 cases) found no relationship between breast cancer and 1,25(OH) 2 D but did not examine associations with 25(OH)D (14). The other, larger study (n = 701 cases) found high levels of both metabolites to be nonsignificantly associated with a lower risk of breast cancer overall, although a statistically significant inverse trend for 25(OH)D was observed in women ages z60 years at blood collection (15 …”

Section: Introductionmentioning

confidence: 98%

Serum Levels of Vitamin D Metabolites and Breast Cancer Risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Freedman¹,

Chang²,

Falk³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

147

107

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Experimental and epidemiologic studies suggest that vitamin D metabolites (1,25(OH) 2 D] and its precursor 25-hydroxyvitamin D [25(OH)D]) may reduce breast cancer risk. We examined subsequent breast cancer risk related to serum levels of these metabolites. In a cohort of women ages 55 to 74 years, who donated blood at baseline (1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001) in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we identified 1,005 incident breast cancer cases during follow-up through 2005 (mean time between blood draw and diagnosis, 3.9 years). Noncases (n = 1,005) were frequency matched to the cases based on age and year of entry. Sample weights that accounted for unequal probabilities of selecting cases and noncases were applied to make inferences that reflected the entire Prostate, Lung, Colorectal, and Ovarian cohort. Using Cox proportional hazards modeling, we computed breast cancer relative risks (RR) and 95% confidence intervals (95% CI) by quintile for each metabolite. The RR of breast cancer for the highest quintile of 25(OH)D concentration versus the lowest was 1.04 (95% CI, 0.75-1.45; P trend = 0.81). Similarly, the breast cancer RR for the highest quintile of 1,25(OH) 2 D compared with the lowest was 1.23 (95% CI, 0.91-1.68; P trend = 0.14). Excluding the first 2 years of follow-up did not materially alter these estimates. There was also no evidence of inverse risk in older women (z60 years) versus younger women (<60 years). In this prospective study of postmenopausal women, we did not observe an inverse association between circulating 25(OH)D or 1,25(OH) 2 D and breast cancer risk, although we cannot exclude an association in younger women or with long-term or earlier exposure. (Cancer Epidemiol Biomarkers Prev 2008;17(4):889 -94)

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Prediagnostic Serum Vitamin D and Breast Cancer

Cited by 65 publications

References 20 publications

Plasma 25‐hydroxyvitamin D and premenopausal breast cancer risk in a German case‐control study

Plasma 25‐hydroxyvitamin D and premenopausal breast cancer risk in a German case‐control study

Altered Nuclear Receptor Corepressor Expression Attenuates Vitamin D Receptor Signaling in Breast Cancer Cells

Serum Levels of Vitamin D Metabolites and Breast Cancer Risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

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