Prospective Study of Predictors of Vitamin D Status and Cancer Incidence and Mortality in Men

Giovannucci, Edward; Liu, Yan; Rimm, Eric B.; Hollis, Bruce W.; Fuchs, Charles S.; Stampfer, Meir J.; Willett, Walter C.

doi:10.1093/jnci/djj101

Cited by 935 publications

(846 citation statements)

References 44 publications

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“…Epidemiological studies suggest an increased risk of and mortality from cancer in northern latitudes with reduced UVB exposure, an association possibly mediated by vitamin D (107) . Furthermore, prospective cohorts have demonstrated an inverse association between 25(OH)D and cancers of the colon, breast and prostate (108)(109)(110)(111) with one intervention study reporting a reduced risk of cancer by 60 % (112) with levels >80 nmol/l. Ananthakrishnan et al (12) looked at data from 2809 patients with IBD and a median plasma 25(OH)D level of 65 nmol/l.…”

Section: Vitamin D and Cancer In Crohn's Diseasementioning

confidence: 99%

Optimal vitamin D levels in Crohn's disease: a review

Raftery

O’Sullivan

2014

Proc. Nutr. Soc.

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Vitamin D deficiency is common among patients with Crohn's disease. Serum 25-hydroxyvitamin D (25(OH)D) is the best measure of an individual's vitamin D status and current cut-off ranges for sufficiency are debatable. Several factors contribute to vitamin D deficiency in Crohn's disease. These include inadequate exposure to sunlight, inadequate dietary intake, impaired conversion of vitamin D to its active metabolite, increased catabolism, increased excretion and genetic variants in vitamin D hydroxylation and transport. The effects of low 25(OH)D on outcomes other than bone health are understudied in Crohn's disease. The aim of the present review is to discuss the potential roles of vitamin D and the possible levels required to achieve them. Emerging evidence suggests that vitamin D may have roles in innate and adaptive immunity, in the immune-pathogenesis of Crohn's disease, prevention of Crohn's disease-related hospitalisations and surgery, in reducing disease severity and in colon cancer prevention. The present literature appears to suggest that 25(OH)D concentrations of ≥75 nmol/l may be required for non-skeletal effects; however, further research on optimal levels is required.

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Section: Vitamin D and Cancer In Crohn's Diseasementioning

confidence: 99%

Optimal vitamin D levels in Crohn's disease: a review

Raftery

O’Sullivan

2014

Proc. Nutr. Soc.

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“…Previous studies on Nurses' Health Study and Health Professionals Follow-up Study have described baseline characteristics of cohort participants and incident colorectal cancer cases, and confirmed that our colorectal cancer cases were well representative as a population-based sample. 28,29 We collected paraffin-embedded tissue blocks from hospitals where cohort participants had undergone resections of primary colorectal cancers. We obtained specimens (hematoxylin and eosin (H&E)-stained slides, unstained slides and/or paraffin blocks) from 648 cases (retrieval rate 76%) in the Health Professionals Follow-up Study and 662 cases (retrieval rate 58%) in the Nurses' Health Study.…”

Section: Study Groupmentioning

confidence: 99%

CpG island methylator phenotype-low (CIMP-low) colorectal cancer shows not only few methylated CIMP-high-specific CpG islands, but also low-level methylation at individual loci

et al. 2008

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The CpG island methylator phenotype (CIMP or CIMP-high) with widespread promoter methylation is a distinct phenotype in colorectal cancer. However, the concept of CIMP-low with less extensive CpG island methylation is still evolving. Our aim is to examine whether density of methylation in individual CpG islands was different between CIMP-low and CIMP-high tumors. Utilizing MethyLight technology and 889 population-based colorectal cancers, we quantified DNA methylation (methylation index, percentage of methylated reference) at 14 CpG islands, including 8 CIMP-high-specific loci (CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1). Methylation positivity in each locus was defined as methylation index44. Low-level methylation (methylation index40, o20) in each CIMP-high-specific locus was significantly more common in 340 CIMP-low tumors (1/8-5/8 methylation-positive loci) than 133 CIMP-high tumors (Z6/8 methylation-positive loci) and 416 CIMP-0 tumors (0/8 methylation-positive loci) (Pr0.002). In the other six loci (CHFR, HIC1, IGFBP3, MGMT, MINT31 and WRN), which were not highly specific for CIMP-high, low-level methylation, was not persistently more prevalent in CIMP-low tumors. In conclusion, compared to CIMP-high and CIMP-0 tumors, CIMP-low colorectal cancers show not only few methylated CIMP-high-specific CpG islands, but also more frequent low-level methylation at individual loci. Our data may provide supporting evidence for a difference in pathogenesis of DNA methylation between CIMP-low and CIMP-high tumors. Modern Pathology (2008) 21, 245-255; doi:10.1038/modpathol.3800982; published online 18 January 2008 Keywords: colon cancer; CpG island methylator phenotype; DNA methylation; promoter; MethyLight; CIMP-low Epigenetic aberrations are important mechanisms in human carcinogenesis. 1 A number of tumor suppressor genes are silenced by promoter methylation in colorectal cancers. 1,2 A subset of colorectal cancers have been shown to exhibit widespread promoter methylation, which is referred to as the CpG island methylator phenotype (CIMP). 1,3 CIMPhigh colorectal tumors have a distinct clinical, pathologic and molecular profile, such as associations with proximal tumor location, female sex, poor tumor differentiation, inactive WNT/b-catenin (CTNNB1) and high BRAF and low TP53 mutation rates, 4-6 independent of microsatellite instability status. 7-10 Although controversial, CIMP may have prognostic implications in colorectal cancer. [11][12][13][14] In contrast to CIMP-high in colorectal cancer, the concept of CIMP-low (with less widespread CIMPspecific promoter methylation) is still emerging. 15,16 While CIMP-high colorectal cancer is associated with female sex and BRAF mutation, CIMP-low is associated with KRAS mutation. 17 Thus, CIMP-low cannot be explained by a simple mixture of CIMPhigh and CIMP-0 (CIMP-negative). 17 We have also demonstrated a possible link between CIMP-low, microsatellite instability-low, MGMT methylation and KRAS mutation in colorectal cancer. 18 18q loss of heterozy...

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“…Some 17 studies reported inverse associations between pre-diagnostic vitamin D concentrations and all-18 cancer mortality [12], mortality from colorectal cancer [23,24], prostate cancer [25], and some 19 studies have shown inverse associations between vitamin D concentration at cancer diagnosis and 20 survival [26,27], but not all studies fully support an inverse association [22,23,28]. A cohort analysis 21 that relied on vitamin D status indicators only, estimated that cancer mortality might decrease by 22 29% with an increase in 25(OH)D concentration of 25 nmol/L [29]. Other studies looked at cancer 23 incidence instead of mortality.…”

Section: Introductionmentioning

confidence: 99%

“…Two 10 studies have previously reported moderate [Pearson r = 0.45; [31]] to high [Pearson r = 0.70; [29]] 11 correlations between vitamin D measurements three years apart. In the InCHIANTI study [31], 12 participants with vitamin D levels above and below the median at both blood draws taken three 13 years apart had the lowest and highest rates of mortality, respectively.…”

Section: Introductionmentioning

confidence: 99%

Inverse association between circulating vitamin D and mortality – Dependent on sex and cause of death?

Rohrmann

Braun

Bopp

et al. 2013

Nutrition, Metabolism and Cardiovascular Diseases

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Prospective Study of Predictors of Vitamin D Status and Cancer Incidence and Mortality in Men

Abstract: Low levels of vitamin D may be associated with increased cancer incidence and mortality in men, particularly for digestive-system cancers. The vitamin D supplementation necessary to achieve a 25(OH)D increment of 25 nmol/L may be at least 1500 IU/day.

Cited by 935 publications

References 44 publications

Optimal vitamin D levels in Crohn's disease: a review

Optimal vitamin D levels in Crohn's disease: a review

CpG island methylator phenotype-low (CIMP-low) colorectal cancer shows not only few methylated CIMP-high-specific CpG islands, but also low-level methylation at individual loci

Inverse association between circulating vitamin D and mortality – Dependent on sex and cause of death?

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