Association between blood circulating vitamin D and colorectal cancer risk in Asian countries: a systematic review and dose-response meta-analysis

Zhang, Lin; Zou, Huachun; Zhao, Yang; Hu, Chunlei; Atanda, Adejare; Qin, Xuzhen; Jia, Peng; Jiang, Yu; Qi, Zhihong

doi:10.1136/bmjopen-2019-030513

Cited by 37 publications

(27 citation statements)

References 67 publications

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“…We found 35 meta‐analyses that investigated relationships between vitamin D status, as measured by circulating 25OHD and cancer outcomes: 29 on cancer incidence, ( 5,6,11,14,29–53 ) 3 on cancer mortality, (10,54,55 ) and 3 on both ( 13,56,57 ) (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Vitamin D and Clinical Cancer Outcomes: A Review of Meta‐Analyses

2020

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The relationship between vitamin D status or supplementation and cancer outcomes has been examined in several meta-analyses. To address remaining knowledge gaps, we conducted a systematic overview and critical appraisal of pertinent meta-analyses. For meta-analyses of trials, we assessed their quality using AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews), strength of associations using umbrella review methodology and credibility of evidence using GRADE (Grading of Recommendations, Assessment, Development and Evaluation) criteria. Meta-analyses of observational studies reported inverse associations of 25-hydroxyvitamin D with risk of cancer incidence and cancer mortality and, particularly for colorectal cancer, fulfilled some of Bradford-Hill's causation criteria. In meta-analyses of trials, vitamin D supplementation did not affect cancer incidence. However, we found credible evidence that vitamin D supplementation reduced total cancer mortality risk, with 5 out of 6 meta-analyses reporting a relative risk (RR) reduction of up to 16%: RR=0.84 (95% confidence interval: 0.74-0.95). The strength of the association, however, was classified as weak. This was true among meta-analyses of high, moderate and lower quality (AMSTAR-2-rated). Trials did not include large numbers of vitamin D-deficient participants, many tested relatively low doses and lacked sufficiently powered data on sitespecific cancers. In conclusion, meta-analyses show that, while observational evidence indicates that low vitamin D status is associated with a higher risk of cancer outcomes, randomized trials demonstrate that vitamin D supplementation reduces total cancer mortality but not cancer incidence. However, trials with larger proportions of vitamin D-insufficient This article is protected by copyright. All rights reserved. participants and longer durations of follow-up, plus adequately powered data on site-specific common cancers, would provide further insight into the evidence base.

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Section: Resultsmentioning

confidence: 99%

Vitamin D and Clinical Cancer Outcomes: A Review of Meta‐Analyses

2020

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“…Holiday sun exposure before melanoma diagnosis has been reported to be associated with lower thickness and the exposure after melanoma diagnosis was also associated with reduce melanoma recurrence 101 . Furthermore, increasing evidence has been suggested that circulating levels of vitamin D may play a protective role against several types of cancer such a bladder 102 and colorectal 103 . Also, a recent pooled analysis of two randomized controlled trials (RCTs) and a prospective cohort found that higher 25(OH)D levels were inversely associated with breast cancer risk with levels ≥ 60 ng/ml ((≥ 150 nmol/L) being most protective 104 .…”

Section: Discussionmentioning

confidence: 99%

25-Hydroxyvitamin D status, vitamin D intake, and skin cancer risk: a systematic review and dose–response meta-analysis of prospective studies

Mahamat‐Saleh

Aune

Schlesinger

2020

Sci Rep

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Sun exposure is a major environmental risk factor for skin cancers and is also an important source of vitamin D. However, while experimental evidence suggests that vitamin D may have a protective effect on skin cancer risk, epidemiologic studies investigating the influence of 25-hydroxyvitamin D (25(OH)D) level and/or vitamin D intake on skin cancer risk are conflicting. A systematic review and dose-response meta-analyses of prospective studies was conducted to clarify these associations. Relevant studies were identified by searching the PubMed database up to 30th August 2019. Random effects dose-response meta-analyses were used to estimate summary relative risks (SRRs) and 95% confidence intervals (CIs). Overall, thirteen prospective studies were included. Circulating level of 25(OH)D was associated with higher risks of melanoma (SRR (95% CI) per 30 nmol = 1.42 (1.17-1.72)) and keratinocyte cancer (KC) (SRR (95% CI) per 30 nmol/L = 1.30 (1.13-1.49)). The SRR (95% CI) per 30 nmol/L increase in 25(OH) D level was 1.41 (1.19-1.67), and 1.57 (0.64-3.86), for basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), respectively. However, while we found that vitamin D intake (from diet, supplemental and total) was not associated with risks of melanoma and SCC, vitamin D intake was associated with slightly increased BCC risk, albeit with no heterogeneity across skin cancer type. This meta-analysis suggests positive associations between circulating 25(OH) D level and risk of melanoma and KC, however, this finding is most likely confounded by sun exposure. We found no associations between vitamin D intake skin cancers, except positive associations with BCC risk. Skin cancers are the most common type of malignancies in Caucasian populations 1 and their incidence has risen worldwide over the past decades 2-4. Melanoma is the most lethal form of skin cancer 5 , with highest incidence rates observed in Australia and New Zealand, followed by Northern America and Europe, and the lowest rates in Asian and African populations 1. Although keratinocyte cancers (KCs), namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), have low mortality rate, they have relevant impact on quality of life and healthcare costs 6,7. The incidence of skin cancer has been expected to increase over the coming decades due to the increasing intensity of ultraviolet (UV) radiation received at the Earth's surface, which is caused by ozone depletion and global warming 8. Established risk factors for skin cancer include sun exposure 9, which is currently the only factor on which prevention can be based, pigmentary traits 10, and family history of skin cancer 11. However, some dietary factors, such as an antioxidant and anti-inflammatory-rich diet, have been suggested to

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“…Colorectal cancer, particularly in late stages, is associated with vitamin D deficiency [56,[66][67][68][69], also related to 1α-hydroxylase downregulated expression, which is strongly correlated with cancer severity [95] whereas higher circulating levels of 25(OH)D are associated with a decreased risk of colorectal cancer in both Asian (OR: 0.75; 95% CI: 0.58 to 0.97; p = 0.034) [70] and Western populations (p = 0.041) [71].…”

Section: Vitamin D and Cancer: Epidemiological Evidencementioning

confidence: 99%

“…Several observational studies have shown that circulating levels of 25(OH)D, used as surrogate marker for the evaluation of vitamin D status, may be associated with cancer risk [ 5 , 6 , 56 , 57 , 58 , 59 ] and prognosis [ 6 , 60 , 61 , 62 , 63 , 64 , 65 ]. A strong association between low 25(OH)D circulating levels and colorectal [ 6 , 56 , 60 , 61 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ], prostate [ 59 , 62 , 63 , 73 , 74 , 75 , 76 , 77 , 78 , 79 ] and breast [ 52 , 58 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 ] cancer risk has been reported.…”

Section: Vitamin D and Cancer: Epidemiological Evidencementioning

confidence: 99%

Vitamin D-Induced Molecular Mechanisms to Potentiate Cancer Therapy and to Reverse Drug-Resistance in Cancer Cells

et al. 2020

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Increasing interest in studying the role of vitamin D in cancer has been provided by the scientific literature during the last years, although mixed results have been reported. Vitamin D deficiency has been largely associated with various types of solid and non-solid human cancers, and the almost ubiquitous expression of vitamin D receptor (VDR) has always led to suppose a crucial role of vitamin D in cancer. However, the association between vitamin D levels and the risk of solid cancers, such as colorectal, prostate and breast cancer, shows several conflicting results that raise questions about the use of vitamin D supplements in cancer patients. Moreover, studies on vitamin D supplementation do not always show improvements in tumor progression and mortality risk, particularly for prostate and breast cancer. Conversely, several molecular studies are in agreement about the role of vitamin D in inhibiting tumor cell proliferation, growth and invasiveness, cell cycle arrest and inflammatory signaling, through which vitamin D may also regulate cancer microenvironment through the activation of different molecular pathways. More recently, a role in the regulation of cancer stem cells proliferation and short non-coding microRNA (miRNAs) expression has emerged, conferring to vitamin D a more crucial role in cancer development and progression. Interestingly, it has been shown that vitamin D is able not only to potentiate the effects of traditional cancer therapy but can even contribute to overcome the molecular mechanisms of drug resistance—often triggering tumor-spreading. At this regard, vitamin D can act at various levels through the regulation of growth of cancer stem cells and the epithelial–mesenchymal transition (EMT), as well as through the modulation of miRNA gene expression. The current review reconsiders epidemiological and molecular literature concerning the role of vitamin D in cancer risk and tumor development and progression, as well as the action of vitamin D supplementation in potentiating the effects of drug therapy and overcoming the mechanisms of resistance often triggered during cancer therapies, by critically addressing strengths and weaknesses of available data from 2010 to 2020.

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Association between blood circulating vitamin D and colorectal cancer risk in Asian countries: a systematic review and dose-response meta-analysis

Cited by 37 publications

References 67 publications

Vitamin D and Clinical Cancer Outcomes: A Review of Meta‐Analyses

Vitamin D and Clinical Cancer Outcomes: A Review of Meta‐Analyses

25-Hydroxyvitamin D status, vitamin D intake, and skin cancer risk: a systematic review and dose–response meta-analysis of prospective studies

Vitamin D-Induced Molecular Mechanisms to Potentiate Cancer Therapy and to Reverse Drug-Resistance in Cancer Cells

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