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Prediagnostic Plasma 25-Hydroxyvitamin D and Pancreatic Cancer Survival.

ABSTRACT: PURPOSE:Although vitamin D inhibits pancreatic cancer proliferation in laboratory models, the association of plasma 25-hydroxyvitamin D [25(OH)D] with patient survival is largely unexplored. PATIENTS AND METHODS:We analyzed survival among 493 patients from five prospective US cohorts who were diagnosed with pancreatic cancer from 1984 to 2008. We estimated hazard ratios (HRs) for death by plasma level of 25(OH)D (insufficient, < 20 ng/mL; relative insufficiency, 20 to < 30 ng/mL; sufficient ? 30 ng/mL) by using Cox proportional hazards regression models adjusted for age, cohort, race and ethnicity, smoking, diagnosis year, stage, and blood collection month. We also evaluated 30 tagging single-nucleotide polymorphisms in the vitamin D receptor gene, requiring P < .002 (0.05 divided by 30 genotyped variants) for statistical significance. RESULTS:Mean prediagnostic plasma level of 25(OH)D was 24.6 ng/mL, and 165 patients (33%) were vitamin D insufficient. Compared with patients with insufficient levels, multivariable-adjusted HRs for death were 0.79 (95% CI, 0.48 to 1.29) for patients with relative insufficiency and 0.66 (95% CI, 0.49 to 0.90) for patients with sufficient levels (P trend = .01). These results were unchanged after further adjustment for body mass index and history of diabetes (P trend = .02). The association was strongest among patients with blood collected within 5 years of diagnosis, with an HR of 0.58 (95% CI, 0.35 to 0.98) comparing patients with sufficient to patients with insufficient 25(OH)D levels. No single-nucleotide polymorphism at the vitamin D receptor gene met our corrected significance threshold of P < .002; rs7299460 was most strongly associated with survival (HR per minor allele, 0.80; 95% CI, 0.68 to 0.95; P = .01). CONCLUSION:We observed longer overall survival in patients with pancreatic cancer who had sufficient prediagnostic plasma levels of 25(OH)D.

SUBMITTER: Yuan C

PROVIDER: S-EPMC5012662 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Prediagnostic Plasma 25-Hydroxyvitamin D and Pancreatic Cancer Survival.

Yuan Chen C Qian Zhi Rong ZR Babic Ana A Morales-Oyarvide Vicente V Rubinson Douglas A DA Kraft Peter P Ng Kimmie K Bao Ying Y Giovannucci Edward L EL Ogino Shuji S Stampfer Meir J MJ Gaziano John Michael JM Sesso Howard D HD Buring Julie E JE Cochrane Barbara B BB Chlebowski Rowan T RT Snetselaar Linda G LG Manson JoAnn E JE Fuchs Charles S CS Wolpin Brian M BM

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20160620 24

<h4>Purpose</h4>Although vitamin D inhibits pancreatic cancer proliferation in laboratory models, the association of plasma 25-hydroxyvitamin D [25(OH)D] with patient survival is largely unexplored.<h4>Patients and methods</h4>We analyzed survival among 493 patients from five prospective US cohorts who were diagnosed with pancreatic cancer from 1984 to 2008. We estimated hazard ratios (HRs) for death by plasma level of 25(OH)D (insufficient, < 20 ng/mL; relative insufficiency, 20 to < 30 ng/mL; ...[more]

PMID: 27325858

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Project description:Laboratory studies suggest that vitamin D may inhibit pancreatic cancer cell growth. However, epidemiologic studies of vitamin D and pancreatic cancer risk have been conflicting.To determine whether prediagnostic levels of plasma 25-hydroxyvitamin D (25[OH]D; IDS Inc.; enzyme immunoassay) were associated with risk of pancreatic cancer, we conducted a pooled analysis of nested case-control studies with 451 cases and 1,167 controls from five cohorts through 2008. Median follow-up among controls was 14.1 years in Health Professionals Follow-Up Study (HPFS), 18.3 years in Nurses' Health Study (NHS), 25.3 years in Physicians' Health Study (PHS), 12.2 years in Women's Health Initiative-Observational Study (WHI), and 14.4 years in Women's Health Study (WHS). Logistic regression was used to compare the odds of pancreatic cancer by plasma level of 25(OH)D.Mean plasma 25(OH)D was lower in cases versus controls (61.3 vs. 64.5 nmol/L, P = 0.005). In logistic regression models, plasma 25(OH)D was inversely associated with odds of pancreatic cancer. Participants in quintiles two through five had multivariable-adjusted ORs (95% confidence intervals) of 0.79 (0.56-1.10), 0.75 (0.53-1.06), 0.68 (0.48-0.97), and 0.67 (0.46-0.97; P(trend) = 0.03), respectively, compared with the bottom quintile. Compared with those with insufficient levels [25[OH]D, <50 nmol/L], ORs were 0.75 (0.58-0.98) for subjects with relative insufficiency [25[OH]D, 50 to <75 nmol/L] and 0.71 (0.52-0.97) for those with sufficient levels [25[OH]D, ? 75 nmol/L]. No increased risk was noted in subjects with 25(OH)D ?100 nmol/L, as suggested in a prior study. In subgroup analyses, ORs for the top versus bottom quartile of 25(OH)D were 0.72 (0.48-1.08) for women, 0.73 (0.40-1.31) for men, and 0.73 (0.51-1.03) for Whites.Among participants in five large prospective cohorts, higher plasma levels of 25(OH)D were associated with a lower risk for pancreatic cancer.Low circulating 25(OH)D may predispose individuals to the development of pancreatic cancer.

Project description:BackgroundAlthough vitamin D inhibits breast tumor growth in experimental settings, the findings from population-based studies remain inconclusive. Our goals were to investigate the association between prediagnostic plasma 25-hydroxyvitamin D [25(OH)D] concentration and breast cancer recurrence in prospective epidemiologic studies and to explore the molecular underpinnings linking 25(OH)D to slower progression of breast cancer in the Nurses' Health Studies (NHS, N = 659).MethodsPlasma 25(OH)D was measured with a high-affinity protein-binding assay and a radioimmunoassay. We profiled transcriptome-wide gene expression in breast tumors using microarrays. Hazard ratios (HR) of breast cancer recurrence were estimated from covariate-adjusted Cox regressions. We examined differential gene expression in association with 25(OH)D and employed pathway analysis. We derived a gene expression score for 25(OH)D, and assessed associations between the score and cancer recurrence.ResultsAlthough 25(OH)D was not associated with breast cancer recurrence overall [HR = 0.97; 95% confidence interval (CI), 0.88-1.08], the association varied by estrogen-receptor (ER) status (P interaction = 0.005). Importantly, among ER-positive stage I to III cancers, every 5 ng/mL increase in 25(OH)D was associated with a 13% lower risk of recurrence (HR = 0.87; 95% CI, 0.76-0.99). A null association was observed for ER-negative cancers (HR = 1.07; 95% CI, 0.91-1.27). Pathway analysis identified multiple gene sets that were significantly (FDR < 5%) downregulated in ER-positive tumors of women with high 25(OH)D (≥30 ng/mL), compared with those with low levels (<30 ng/mL). These gene sets are primarily involved in tumor proliferation, migration, and inflammation. 25(OH)D score derived from these gene sets was marginally associated with reduced risk of recurrence in ER-positive diseases (HR = 0.77; 95% CI, 0.59-1.01) in the NHS studies; however no association was noted in METABRIC, suggesting that further refinement is need to improve the generalizability of the score.ConclusionsOur findings support an intriguing line of research for studies to better understand the mechanisms underlying the role of vitamin D in breast tumor progression, particularly for the ER-positive subtype.ImpactVitamin D may present a personal-level secondary-prevention strategy for ER-positive breast cancer.

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Prediagnostic Plasma 25-Hydroxyvitamin D and Pancreatic Cancer Survival.

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Prediagnostic Plasma 25-Hydroxyvitamin D and Pancreatic Cancer Survival.

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