Circulating Vitamin D and Colorectal Cancer Risk: An International Pooling Project of 17 Cohorts

McCullough, Marjorie L.; Zoltick, Emilie S.; Weinstein, Stephanie J.; Fedirko, Veronika; Wang, Molin; Cook, Nancy R.; Eliassen, A. Heather; Zeleniuch‐Jacquotte, Anne; Agnoli, Claudia; Albanês, Demetrius; Barnett, Matthew J; Buring, Julie E.; Campbell, Peter T.; Clendenen, Tess V.; Freedman, Neal D.; Gapstur, Susan M.; Giovannucci, Edward; Goodman, Gary; Haiman, Christopher A.; Ho, Gloria Y.F.; Horst, Ronald L.; Hou, Tao; Huang, Wen‐Yi; Jenab, Mazda; Jones, Michael E.; Joshu, Corinne E.; Krogh, Vittorio; Lee, I-Min; Lee, Jung Eun; Männistö, Satu; Marchand, Loı̈c Le; Mondul, Alison M.; Neuhouser, Marian L.; Platz, Elizabeth A.; Purdue, Mark P.; Riboli, Elio; Robsahm, Trude Eid; Rohan, Thomas E.; Sasazuki, Shizuka; Schoemaker, Minouk J.; Sieri, Sabina; Stampfer, Meir J.; Swerdlow, Anthony; Thomson, Cynthia A.; Tretli, Steinar; Tsugane, S; Ursin, Giske; Visvanathan, Kala; White, Kami; Wu, Kana; Yaun, Shiaw-Shyuan; Zhang, Xuehong; Willett, Walter C.; Gail, M; Ziegler, Regina G.; Smith‐Warner, Stephanie A.

doi:10.1093/jnci/djy087

Cited by 216 publications

(182 citation statements)

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“…However, individuals in the CopD study cohort were younger, and therefore the results are not directly comparable. Also, a large case–control study based on pooling of 17 cohorts showed a protective effect of higher vitamin D levels with regards to the risk of colon‐rectosigmoidal cancers in women. We do not find incident colon‐rectosigmoidal cancers to be associated with the level of vitamin D, neither in women only.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D levels and cancer incidence in 217,244 individuals from primary health care in Denmark

Vojdeman

Madsen

Frederiksen

et al. 2019

Intl Journal of Cancer

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Vitamin D has been linked to cancer development in both pre‐clinical and epidemiological studies. Our study examines the association between serum levels of vitamin D and cancer incidence in the Capital Region of Denmark. Individuals who had vitamin D analyzed at The Copenhagen General Practitioners Laboratory between April 2004 and January 2010 were linked to Danish registries with end of follow‐up date at Dec 31st 2014, excluding individuals with pre‐existing cancer. Cox regression models adjusted for age in one‐year intervals, sex, month of sampling, and Charlson Comorbidity Index were applied. The study population of 217,244 individuals had a median vitamin D level of 46 nmol/L (IQR 27–67 nmol/L). Non‐melanoma skin cancer was the most frequent form of cancer, followed by breast‐, lung‐, and prostate cancers. No associations were found between increments of 10 nmol/L vitamin D and incidence of breast, colorectal, urinary, ovary or corpus uteri cancer. However, higher levels of vitamin D were associated with higher incidence of non‐melanoma (HR 1.09 [1.09–1.1]) and melanoma skin cancer (HR 1.1 [1.08–1.13]) as well as prostate (HR 1.05 [1.03–1.07]) and hematological cancers (HR 1.03 [1.01–1.06]), but with lower incidence of lung cancer (HR 0.95 [0.93–0.97]). In our study, vitamin D levels are not associated with the incidence of several major cancer types, but higher levels are significantly associated with a higher incidence of skin, prostate, and hematological cancers as well as a lower incidence of lung cancer. These results do not support an overall protective effect against cancer by vitamin D.

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Section: Discussionmentioning

confidence: 99%

Vitamin D levels and cancer incidence in 217,244 individuals from primary health care in Denmark

Vojdeman

Madsen

Frederiksen

et al. 2019

Intl Journal of Cancer

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“…Appropriate serum 25(OH)D levels for disease prevention were different in observational studies, and the ideal level has not been examined for Graves' disease. For example, the risk of colorectal cancer was lowest in individuals with vitamin D levels >30 ng/mL 24 , and for cardiovascular diseases, the optimal vitamin D level ranged from 20 to 25 ng/mL 6 . Thus, further interventions are needed to identify the optimal vitamin D status for improving clinical outcomes of Graves' disease.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D supplementation does not prevent the recurrence of Graves’ disease

Cho

Chung

2020

Sci Rep

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Recent literature has reported a higher prevalence of vitamin D deficiency among people with Graves' disease. No study has examined the effect of vitamin D supplementation on the clinical outcomes of Graves' disease. We aimed to evaluate whether daily vitamin D supplementation reduces Graves' disease recurrence. We enrolled 210 subjects with Graves' disease and vitamin D deficiency and followed them for at least one year after anti-thyroid drug (ATD) discontinuation. Among 210 individuals, 60 (29%) were amenable to taking vitamin D supplements, resulting in sufficient vitamin D levels (from 10.6 to 25.7 ng/mL), whereas the mean vitamin D level was 11.6 ng/mL in the 150 patients who did not take vitamin D supplements. The recurrence rate was similar in both groups (38% vs. 49%, P = 0.086). However, recurrence occurred earlier in the latter group (7 months vs. 5 months, P = 0.016). In the multivariate analysis, vitamin D levels and TSH-binding inhibitory immunoglobulin (TBII) titers at ATD discontinuation remained significant factors for recurrence. Vitamin D levels and TBII titers at ATD discontinuation exhibited a weak negative correlation (R = −0.143, P = 0.041). Vitamin D supplementation might have a protective effect against Graves' disease recurrence with a borderline significant recurrence rate reduction. Autoimmune thyroid diseases (AITDs), including Graves' disease and Hashimoto's thyroiditis, are the most common organ-specific autoimmune disorders 1. AITDs are caused by various environmental triggers, such as iodine, drugs, radiation, and infection in genetically predisposed individuals 2. AITDs are characterized by T-cell-mediated autoimmune diseases, and Graves' disease is primarily related to hyperactive humoural responses that lead to the production of stimulatory autoantibodies for the thyroid stimulating hormone (TSH) receptor 1. Vitamin D regulates bone metabolism and the homeostasis of calcium and phosphorus. The active form of vitamin D binds to the nuclear vitamin D receptor (VDR) and controls the expression of over 200 genes responsible for the regulation of cell proliferation, differentiation, and apoptosis in most tissues and cells, including immune cells 3. Non-skeletal actions of vitamin D have been studied over the past few decades, and evidence suggests that there is a relationship between vitamin D deficiency and various diseases, such as autoimmune diseases 4 , cardiovascular disease 5,6 , and cancer 5,7. Recent studies have reported that low vitamin D levels are prevalent in patients with Graves' disease. Kivity et al. observed a higher prevalence of vitamin D deficiency (defined as 25-hydroxyvitamin(OH)D < 10 ng/mL) in 22 Graves' disease patients compared with 98 healthy controls (64% vs. 30%, P < 0.01) 8. Yasuda et al. reported reduced levels of vitamin D in 26 Graves' disease patients compared to the levels in 46 controls (25(OH)D 3 levels of 14.4 ng/mL vs. 17.1 ng/mL, P < 0.05) 9. Two meta-analyses implicated vitamin D deficiency as a risk factor for Graves' disease 4,10 , although...

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“…Equal amounts of protein were separated by SDS-polyacrylamide gel electrophoresis and were transferred to nitrocellulose membranes. The non-specific sites were blocked with 5% bovine serum albumin (34) in TBST (50 mM Tris, 150 mM NaCl, and 0.05% Tween 20 adjusted to pH 7.6 with HCl), and the membranes were then incubated with dilutions of the primary antibodies as recommended by the manufacturers. The primary antibodies included the following: anti-p62 (1:1,000, AP2183B, ABGENT, San Diego, CA,USA); anti-LC3B (1:1,000, 2775), anti-SAPK/JNK (1:1,000, 9258), antiphospho-SAPK/JNK (Thr183/Tyr185, 1:1,000, 9251), anti-cjun (60A8, 1:1,000, 9165), anti-phospho-c-jun (S63, 1:1,000, 9261) (Cell Signaling, Beverly, MA, USA); anti-BECN1/Beclin-1 (1:1,000, SC-10086), anti-c-myc (PE10, 1:1,000, SC-40), anti-HA-probe (F-7, 1:1,000, SC-7392) (Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA); anti-β-actin (1:2,000, A5441, Sigma-Aldrich, Milwaukee, WI, USA); anti-ubiquitin (1:1,000, UG9511, ENZO, Farmingdale, NY, USA); and anti-AvrA [1:1,000, custommade, as reported in our previous studies (35)].…”

Section: Immunoblotting and Antibodiesmentioning

confidence: 99%

Salmonella Enteritidis Effector AvrA Suppresses Autophagy by Reducing Beclin-1 Protein

et al. 2020

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Autophagy is a cellular process to clear pathogens. Salmonella enterica serovar Enteritidis (S.E) has emerged as one of the most important food-borne pathogens. However, major studies still focus on Salmonella enterica serovar Typhimurium. Here, we reported that AvrA, a S. Enteritidis effector, inhibited autophagy to promote bacterial survival in the host. We found that AvrA regulates the conversion of LC3 I into LC3 II and the enrichment of lysosomes. Beclin-1, a key molecular regulator of autophagy, was decreased after AvrA expressed strain colonization. In S.E-AvrA − -infected cells, we found the increases of protein levels of p-JNK and p-c-Jun and the transcription level of AP-1. AvrA-reduction of Beclin-1 protein expression is through the JNK pathway. The JNK inhibitor abolished the AvrA-reduced Beclin-1 protein expression. Moreover, we identified that the AvrA mutation C186A abolished its regulation of Beclin-1 expression. In addition AvrA protein was found interacted with Beclin-1. In organoids and infected mice, we explored the physiologically related effects and mechanism of AvrA in reducing Beclin-1 through the JNK pathway, thus attenuating autophagic responses. This finding not only indicates an important role of S. Enteritidis effector in reducing host protein as a strategy to suppress autophagy, but also suggests manipulating autophagy as a new strategy to treat infectious diseases.

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Circulating Vitamin D and Colorectal Cancer Risk: An International Pooling Project of 17 Cohorts

Cited by 216 publications

References 50 publications

Vitamin D levels and cancer incidence in 217,244 individuals from primary health care in Denmark

Vitamin D levels and cancer incidence in 217,244 individuals from primary health care in Denmark

Vitamin D supplementation does not prevent the recurrence of Graves’ disease

Salmonella Enteritidis Effector AvrA Suppresses Autophagy by Reducing Beclin-1 Protein

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