Circulating 25-Hydroxyvitamin D Concentration and Risk of Breast, Prostate, and Colorectal Cancers: The Melbourne Collaborative Cohort Study

Heath, Alicia K.; Hodge, Allison; Ebeling, Peter R.; Eyles, Darryl W.; Kvaskoff, David; Buchanan, Daniel D.; Giles, Graham G.; Williamson, Elizabeth; English, Dallas R.

doi:10.1158/1055-9965.epi-18-1155

Cited by 25 publications

(18 citation statements)

References 42 publications

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“…The highly similar effect of calcitriol on colon tumor and rectal tumor organoids is consistent with the finding that colon and rectal cancers, excluding hypermutated cancers, have similar patterns of genetic alterations [ 65 ]. Moreover, our finding also agrees with the proposed protective effect of vitamin D on both colon and rectal cancers [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

Section: Discussionsupporting

confidence: 92%

“…The gut physiology is profoundly affected by the action of vitamin D [ 17 ], and observational studies have established a link between vitamin D deficiency and an elevated risk and poor prognosis of CRC, suggesting that colon and rectal cancer patients might preferentially benefit from an adequate vitamin D status [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. Data from recent interventional clinical studies indicate that the addition of vitamin D to standard chemotherapy improves the progression-free survival of metastatic CRC patients [ 29 ]; however, another randomized trial showed no preventive effect on adenoma recurrence [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

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Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue

Costales-Carrera

Fernández‐Barral

Bustamante-Madrid

et al. 2020

Cancers

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Colon and rectal tumors, often referred to as colorectal cancer, show different gene expression patterns in studies that analyze whole tissue biopsies containing a mix of tumor and non-tumor cells. To better characterize colon and rectal tumors, we investigated the gene expression profile of organoids generated from endoscopic biopsies of rectal tumors and adjacent normal colon and rectum mucosa from therapy-naive rectal cancer patients. We also studied the effect of vitamin D on these organoid types. Gene profiling was performed by RNA-sequencing. Organoids from a normal colon and rectum had a shared gene expression profile that profoundly differed from that of rectal tumor organoids. We identified a group of genes of the biosynthetic machinery as rectal tumor organoid-specific, including those encoding the RNA polymerase II subunits POLR2H and POLR2J. The active vitamin D metabolite 1α,25-dihydroxyvitamin D3/calcitriol upregulated stemness-related genes (LGR5, LRIG1, SMOC2, and MSI1) in normal rectum organoids, while it downregulated differentiation marker genes (TFF2 and MUC2). Normal colon and rectum organoids share similar gene expression patterns and respond similarly to calcitriol. Rectal tumor organoids display distinct and heterogeneous gene expression profiles, with differences with respect to those of colon tumor organoids, and respond differently to calcitriol than normal rectum organoids.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue

Costales-Carrera

Fernández‐Barral

Bustamante-Madrid

et al. 2020

Cancers

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“…Evidence over the past decades supports that vitamin D has a beneficial effect on colorectal cancer (CRC) development and outcome [ 1 – 4 ]. The primary circulating form of vitamin D, 25-hydroxyvitamin D [25(OH) D], is mainly dependent on the exposure to ultraviolet B solar radiation, and levels are therefore depleted during the winter season at high latitudes unless the dietary supplementation is adequate [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Sex disparities in vitamin D status and the impact on systemic inflammation and survival in rectal cancer

et al. 2021

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Background We reported previously that rectal cancer patients given curative-intent chemotherapy, radiation, and surgery for non-metastatic disease had enhanced risk of metastatic progression and death if circulating levels of 25-hydroxyvitamin D [25(OH) D] were low. Here we investigated whether the association between the vitamin D status and prognosis pertains to the general, unselected population of rectal cancer patients. Methods Serum 25(OH) D at the time of diagnosis was assessed in 129 patients, enrolled 2013–2017 and representing the entire range of rectal cancer stages, and analyzed with respect to season, sex, systemic inflammation, and survival. Results In the population-based cohort residing at latitude 60°N, 25(OH) D varied according to season in men only, who were overrepresented among the vitamin D-deficient (< 50 nmol/L) patients. Consistent with our previous findings, the individuals presenting with T4 disease had significantly reduced 25(OH) D levels. Low vitamin D was associated with systemic inflammation, albeit with distinct modes of presentation. While men with low vitamin D showed circulating markers typical for the systemic inflammatory response (e.g., elevated erythrocyte sedimentation rate), the corresponding female patients had elevated serum levels of interleukin-6 and the chemokine (C-X-C motif) ligand 7. Despite disparities in vitamin D status and the potential effects on disease attributes, significantly shortened cancer-specific survival was observed in vitamin D-deficient patients irrespective of sex. Conclusion This unselected rectal cancer cohort confirmed the interconnection of low vitamin D, more advanced disease presentation, and poor survival, and further suggested it may be conditional on disparate modes of adverse systemic inflammation in men and women. Trial registration ClinicalTrials.govNCT01816607; registration date: 22 March 2013.

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“…Observational studies have identified several risk factors associated with an increased incidence of colorectal cancer including lifestyle factors (eg, obesity, physical inactivity, smoking and heavy alcohol use) and non-modifiable factors (eg, ageing, personal and family history of colorectal cancer or adenoma) 3. Other observational studies conducted in Western countries suggest blood circulating 25-hydroxyvitamin D (25(OH)D) (vitamin D) has a protective role in the development of colorectal cancer 4–8. Some meta-analyses have consistently reported that there was an inverse association between plasma vitamin D concentration in the blood and incidence of, and mortality from, colorectal cancer 9–15…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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ObjectivesTo assess the association between blood circulating vitamin D levels and colorectal cancer risk in the Asian population.DesignThis is a systematic review and dose-response meta-analysis of observational studies that investigated the relationship between blood circulating vitamin D levels and colorectal cancer risk in the Asian population.Data sourcesRelevant studies were identified through a literature search in Medline, Embase and Web of Science from 1st January 1980 to 31st January 2019. Eligibility criteria: original studies published in peer-reviewed journals investigating the association between blood circulating vitamin D levels and the risk of colorectal cancer and/or adenoma in Asian countries.Data extraction and synthesisTwo authors independently extracted data and assessed the quality of included studies. Study-specific ORs were pooled using a random-effects model. A dose-response meta-analysis was performed with generalised least squares regression. We applied the Newcastle-Ottawa Scale quality assessment to evaluate the quality of the selected studies.ResultsThe eight included studies encompassed a total of 2916 cases and 6678 controls. The pooled ORs of colorectal cancer for the highest versus lowest categories of blood circulating vitamin D levels was 0.75 (95% CI 0.58 to 0.97) up to 36.5 ng/mL in the Asian population. There was heterogeneity among the studies (I2=53.9%,Pheterogeneity=0.034). The dose-response meta-analysis indicated a significant linear relationship (Pnon-linearity=0.11). An increment of 16 ng/mL in blood circulating vitamin D level corresponded to an OR of 0.79 (95% CI 0.64 to 0.97).ConclusionsThe results of this meta‐analysis indicate that blood circulating vitamin D level is associated with decreased risk of colorectal cancer in Asian countries. The dose-response meta-analysis shows that the strength of this association among the Asian population is similar to that among the Western population. Our study suggests that the Asian population should improve nutritional status and maintain a higher level of blood circulating vitamin D.

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Circulating 25-Hydroxyvitamin D Concentration and Risk of Breast, Prostate, and Colorectal Cancers: The Melbourne Collaborative Cohort Study

Cited by 25 publications

References 42 publications

Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue

Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue

Sex disparities in vitamin D status and the impact on systemic inflammation and survival in rectal cancer

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

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