Cedric F. Garland’s research while affiliated with University of California, San Diego and other places

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Publications (211)


Estimated crude incidence rates of CRC in 0–14 years of age by UVB estimates, 2018
Estimated crude incidence rates of CRC in 15–29 years of age by UVB estimates, 2018
Estimated crude incidence rates of CRC in 30–44 years of age by UVB estimates, 2018
Estimated crude incidence rates of CRC in 45–59 years of age by UVB estimates, 2018
Estimated crude incidence rates of CRC in 60–74 years of age by UVB estimates, 2018

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Could age increase the strength of inverse association between ultraviolet B exposure and colorectal cancer?
  • Article
  • Full-text available

July 2021

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50 Reads

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8 Citations

BMC Public Health

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Cedric F Garland

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Background Vitamin D has been identified as a potential protective factor in the development of colorectal cancer (CRC). We expect to see a stronger association of ultraviolet B (UVB) exposure and CRC crude rates with increasing age since chronic vitamin D deficiency leads to sustained molecular changes that increase cancer risk. The DINOMIT (disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition) model postulates various stages of cancer development due to vitamin D deficiency and the associated latency period. The purpose of this study is to examine this age-dependent inverse relationship globally. Methods In this ecological study, a series of linear and polynomial regression tests were performed between country-specific UVB estimates adjusted for cloud cover and crude incidence rates of CRC for different age groups. Multiple linear regression was used to investigate the association between crude incidence rates of colorectal cancer and UVB estimate adjusting for urbanization, skin pigmentation, smoking, animal consumption, per capita GDP, and life expectancy. Statistical analysis was followed by geospatial visualization by producing choropleth maps. Results The inverse relationship between UVB exposure and CRC crude rates was stronger in older age groups at the country level. Quadratic curve fitting was preferred, and these models were statistically significant for all age groups. The inverse association between crude incidence rates of CRC and UVB exposure was statistically significant for age groups above 45 years, after controlling for covariates. Conclusion The age-dependent inverse association between UVB exposure and incidence of colorectal cancer exhibits a greater effect size among older age groups in global analyses. Studying the effect of chronic vitamin D deficiency on colorectal cancer etiology will help in understanding the necessity for population-wide screening programs for vitamin D deficiency, especially in regions with inadequate UVB exposure. Further studies are required to assess the need for adequate public health programs such as selective supplementation and food fortification.

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UVB estimate in association with crude incidence rate of CRC using linear regression
UVB estimate in association with crude incidence rate of CRC using polynomial regression
Could age increase the strength of inverse association between ultraviolet B exposure and colorectal cancer?

November 2020

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31 Reads

Background: Vitamin D has been identified as a potential protective factor the development of colorectal cancer (CRC). We expect to see a stronger association of ultraviolet B (UVB) exposure and CRC crude rates with increasing age since chronic vitamin D deficiency leads to sustained molecular changes that increase cancer risk. The DINOMIT (disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition) model postulates various stages of cancer development due to vitamin D deficiency and the associated latency period. The purpose of this study is to examine this age-dependent inverse relationship globally. Methods: In this ecological study, a series of linear and polynomial regression tests were performed between country specific UVB estimates adjusted for cloud cover and crude incidence rates of CRC for different age groups. Multiple linear regression was used to investigate the association between crude incidence rates of colorectal cancer and UVB estimate adjusting for urbanization, skin pigmentation, smoking, animal consumption, per capita GDP, and life expectancy. Statistical analysis was followed by geospatial visualization by producing choropleth maps. Results: The inverse relationship between UVB exposure and CRC crude rates was stronger in older age groups at the country level. Quadratic curve fitting was preferred, and these models were statistically significant for all age groups. The inverse association between crude incidence rates of CRC and UVB exposure was statistically significant for age groups above 45 years, after controlling for covariates. Conclusion: The age-dependent inverse association between UVB exposure and incidence of colorectal cancer exhibits a greater effect size among older age groups in global analyses. Studying the effect of chronic vitamin D deficiency on colorectal cancer etiology will help in understanding the necessity for population wide screening programs for vitamin D deficiency, especially in regions with inadequate UVB exposure. Further studies are required to assess the need for adequate public health programs such as selective supplementation and food fortification.


Insufficient Sun Exposure Has Become a Real Public Health Problem

July 2020

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1,116 Reads

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128 Citations

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Bruce K. Armstrong

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This article aims to alert the medical community and public health authorities to accumulating evidence on health benefits from sun exposure, which suggests that insufficient sun exposure is a significant public health problem. Studies in the past decade indicate that insufficient sun exposure may be responsible for 340,000 deaths in the United States and 480,000 deaths in Europe per year, and an increased incidence of breast cancer, colorectal cancer, hypertension, cardiovascular disease, metabolic syndrome, multiple sclerosis, Alzheimer’s disease, autism, asthma, type 1 diabetes and myopia. Vitamin D has long been considered the principal mediator of beneficial effects of sun exposure. However, oral vitamin D supplementation has not been convincingly shown to prevent the above conditions; thus, serum 25(OH)D as an indicator of vitamin D status may be a proxy for and not a mediator of beneficial effects of sun exposure. New candidate mechanisms include the release of nitric oxide from the skin and direct effects of ultraviolet radiation (UVR) on peripheral blood cells. Collectively, this evidence indicates it would be wise for people living outside the tropics to ensure they expose their skin sufficiently to the sun. To minimize the harms of excessive sun exposure, great care must be taken to avoid sunburn, and sun exposure during high ambient UVR seasons should be obtained incrementally at not more than 5–30 min a day (depending on skin type and UV index), in season-appropriate clothing and with eyes closed or protected by sunglasses that filter UVR.


Changes in the Dietary Inflammatory Index Over Time and Cancer Development Within Rural Post-Menopausal Women

June 2020

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24 Reads

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2 Citations

Current Developments in Nutrition

Objectives The objective of this study was to determine the extent to which diets with a higher inflammatory potential, as measured by the Dietary Inflammatory Index (DII), are associated with cancer development in a cohort of rural post-menopausal women. Methods This study was a secondary analysis of participants of a randomized control trial evaluating the effect of vitamin D and calcium supplementation on cancer development in rural, post-menopausal women in Nebraska. From this cohort, diets were evaluated via a 2005 Block Food Frequency Questionnaire (FFQ) at baseline and four years later (Visit 9). DII scores were calculated at both time points for each participant, including an unadjusted and energy-adjusted DII score. The relationship with DII scores and cancer development were evaluated using a chi-squared test and logistic regression, controlling for pertinent confounders. The difference in DII scores at baseline and Visit 9 for participants who developed cancer and non-cancer participants was examined via a repeated measure ANOVA test. Results There were 1977 participants with baseline and Visit 9 DII scores available for analysis. There was a significant difference in DII scores between baseline and Visit 9, with a significantly larger change in DII scores in the participants who developed cancer (p = 0.0194), shifting to higher pro-inflammatory scores at Visit 9. Cancer status was not associated with baseline DII scores, nor was DII score a predictor of cancer status, when controlling for confounders. Conclusions These findings illustrate how dietary patterns in persons diagnosed with cancer had significant changes over time, increasing inflammatory diet potential. This increase in inflammatory potential in cancer patients may impact outcomes like treatment success, overall survival, and cancer recurrence, creating a need for more research to further analyze the impact of cancer diagnoses on diet changes, and if these changes are detrimental to cancer survivor outcomes. Funding Sources None.


Figure 2 Estimated Crude incidence rates of CRC in 15-29 years of age by UVB estimates, 2018.
Figure 3 Estimated Crude incidence rates of CRC in 30-44 years of age by UVB estimates, 2018.
Figure 5 Estimated Crude incidence rates of CRC in 60-74 years of age by UVB estimates, 2018.
Correlation between colorectal cancer crude incidence rate and ultraviolet B estimate for every
Could age increase the strength of inverse association between ultraviolet B exposure and colorectal cancer?

January 2020

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49 Reads

Background Vitamin D has been identified as a potential protective factor the development of colorectal cancer (CRC). We expect to see a stronger association of ultraviolet B (UVB) exposure and CRC crude rates with increasing age since chronic vitamin D deficiency leads to sustained molecular changes that increase cancer risk. The DINOMIT (disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition) model postulates various stages of cancer development due to vitamin D deficiency and the associated latency period. The purpose of this study is to examine this age-dependent inverse relationship globally. Methods In this ecological study, a series of linear and polynomial regression tests were performed between country specific UVB estimates adjusted for cloud cover and crude incidence rates of CRC for different age groups. Multiple linear regression was used to investigate the association between crude incidence rates of colorectal cancer and UVB estimate adjusting for urbanization, skin pigmentation, smoking, animal consumption, per capita GDP, and life expectancy. Statistical analysis was followed by geospatial visualization by producing choropleth maps. Results The inverse relationship between UVB exposure and CRC crude rates was stronger in older age groups at the country level. Quadratic curve fitting was preferred, and these models were statistically significant for all age groups. The inverse association between crude incidence rates of CRC and UVB exposure was statistically significant for age groups above 45 years, after controlling for covariates. Conclusion The age-dependent inverse association between UVB exposure and incidence of colorectal cancer exhibits a greater effect size among older age groups in global analyses. Studying the effect of chronic vitamin D deficiency on colorectal cancer etiology will help in understanding the necessity for population wide screening programs for vitamin D deficiency, especially in regions with inadequate UVB exposure. The study supports the need for adequate public health programs such as selective supplementation and food fortification.


Correlation between colorectal cancer crude incidence rate and ultraviolet B estimate for every age group
UVB estimate in association with crude incidence rate of CRC using polynomial regression
UVB estimate in association with crude incidence rate of CRC using linear regression
Could age increase the strength of inverse association between ultraviolet B exposure and colorectal cancer?

January 2020

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29 Reads

Background: Vitamin D has been identified as a potential protective factor the development of colorectal cancer (CRC). We expect to see a stronger association of ultraviolet B (UVB) exposure and CRC crude rates with increasing age since chronic vitamin D deficiency leads to sustained molecular changes that increase cancer risk. The DINOMIT (disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition) model postulates various stages of cancer development due to vitamin D deficiency and the associated latency period. The purpose of this study is to examine this age-dependent inverse relationship globally. Methods: In this ecological study, a series of linear and polynomial regression tests were performed between country specific UVB estimates adjusted for cloud cover and crude incidence rates of CRC for different age groups. Multiple linear regression was used to investigate the association between crude incidence rates of colorectal cancer and UVB estimate adjusting for urbanization, skin pigmentation, smoking, animal consumption, per capita GDP, and life expectancy. Statistical analysis was followed by geospatial visualization by producing choropleth maps. Results: The inverse relationship between UVB exposure and CRC crude rates was stronger in older age groups at the country level. Quadratic curve fitting was preferred, and these models were statistically significant for all age groups. The inverse association between crude incidence rates of CRC and UVB exposure was statistically significant for age groups above 45 years, after controlling for covariates. Conclusion: The age-dependent inverse association between UVB exposure and incidence of colorectal cancer exhibits a greater effect size among older age groups in global analyses. Studying the effect of chronic vitamin D deficiency on colorectal cancer etiology will help in understanding the necessity for population wide screening programs for vitamin D deficiency, especially in regions with inadequate UVB exposure. Further studies are required to assess the need for adequate public health programs such as selective supplementation and food fortification.


UVB estimate in association with crude incidence rate of CRC using linear
UVB estimate in association with crude incidence rate of CRC using polynomial
Could age increase the strength of inverse association between ultraviolet B exposure and colorectal cancer?

January 2020

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40 Reads

Background: Vitamin D has been identified as a potential protective factor the development of colorectal cancer (CRC). We expect to see a stronger association of ultraviolet B (UVB) exposure and CRC crude rates with increasing age since chronic vitamin D deficiency leads to sustained molecular changes that increase cancer risk. The DINOMIT (disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition) model postulates various stages of cancer development due to vitamin D deficiency and the associated latency period. The purpose of this study is to examine this age-dependent inverse relationship globally. Methods: In this ecological study, a series of linear and polynomial regression tests were performed between country specific UVB estimates adjusted for cloud cover and crude incidence rates of CRC for different age groups. Multiple linear regression was used to investigate the association between crude incidence rates of colorectal cancer and UVB estimate adjusting for urbanization, skin pigmentation, smoking, animal consumption, per capita GDP, and life expectancy. Statistical analysis was followed by geospatial visualization by producing choropleth maps. Results: The inverse relationship between UVB exposure and CRC crude rates was stronger in older age groups at the country level. Quadratic curve fitting was preferred, and these models were statistically significant for all age groups. The inverse association between crude incidence rates of CRC and UVB exposure was statistically significant for age groups above 45 years, after controlling for covariates. Conclusion: The age-dependent inverse association between UVB exposure and incidence of colorectal cancer exhibits a greater effect size among older age groups in global analyses. Studying the effect of chronic vitamin D deficiency on colorectal cancer etiology will help in understanding the necessity for population wide screening programs for vitamin D deficiency, especially in regions with inadequate UVB exposure. Further studies are required to assess the need for adequate public health programs such as selective supplementation and food fortification.


Abstract P6-10-02: Not presented

February 2019

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20 Reads

This abstract was not presented at the conference. Citation Format: McDonnell SL, Baggerly CA, French CB, Baggerly LL, Garland CF, Gorham ED, Lappe JM. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-10-02.



Frequency distribution and breast cancer incidence rates by 25(OH)D concentration, pooled cohort (N = 5038)
The bars represent the number of participants by groupings of 10 ng/ml (left y-axis), white dots represent the 25(OH)D concentration for each breast cancer case, black dots represent breast cancer incidence rates per 100,000 person-years for each 25(OH)D group (plotted at the median value for each group: 16, 25, 32, 39, 47, 57, and 70 ng/ml) (right y-axis). Vertical error bars represent the 95% confidence intervals.
Kaplan-Meier plot comparing the proportion of breast cancer-free participants by 25(OH)D concentration, pooled cohort (N = 5038)
Participants were allowed to move between strata of 25(OH)D according to changes in 25(OH)D concentration over the course of the observation periods. Four-year cumulative breast cancer-free proportion was 99.3% among participants with 25(OH)D concentrations ≥60 ng/ml compared to 96.8% for those with 25(OH)D concentrations <20 ng/ml (the proportion with breast cancer was 78% lower for ≥60 ng/ml vs <20 ng/ml, P = 0.02).
Association between serum 25(OH)D (as a continuous variable) and risk of breast cancer adjusted for age, BMI, smoking status, calcium supplement intake, and study of origin in the range of ≤100 ng/ml, pooled cohort (N = 5308)
Solid black line represents the estimated hazard ratio for the Cox regression model with restricted cubic splines with three knots; dashed lines represent the 95% confidence interval of the estimate.
Characteristics of the pooled, 2007 Lappe, 2017 Lappe, and GrassrootsHealth cohorts
Association between serum 25(OH)D and risk of breast cancer, pooled cohort (N = 5038)
Breast cancer risk markedly lower with serum 25-hydroxyvitamin D concentrations ≥60 vs <20 ng/ml (150 vs 50 nmol/L): Pooled analysis of two randomized trials and a prospective cohort

June 2018

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339 Reads

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121 Citations

Background While numerous epidemiologic studies have found an association between higher serum 25-hydroxyvitamin D [25(OH)D] concentrations and lower breast cancer risk, few have assessed this association for concentrations >40 ng/ml. Objective To investigate the relationship between 25(OH)D concentration and breast cancer risk across a broad range of 25(OH)D concentrations among women aged 55 years and older. Methods Analyses used pooled data from two randomized clinical trials (N = 1129, N = 2196) and a prospective cohort (N = 1713) to examine a broad range of 25(OH)D concentrations. The outcome was diagnosis of breast cancer during the observation periods (median: 4.0 years). Three analyses were conducted: 1) Incidence rates were compared according to 25(OH)D concentration from <20 to ≥60 ng/ml (<50 to ≥150 nmol/L), 2) Kaplan-Meier plots were developed and 3) multivariate Cox regression was used to examine the association between 25(OH)D and breast cancer risk using multiple 25(OH)D measurements. Results Within the pooled cohort (N = 5038), 77 women were diagnosed with breast cancer (age-adjusted incidence: 512 cases per 100,000 person-years). Results were similar for the three analyses. First, comparing incidence rates, there was an 82% lower incidence rate of breast cancer for women with 25(OH)D concentrations ≥60 vs <20 ng/ml (Rate Ratio = 0.18, P = 0.006). Second, Kaplan-Meier curves for concentrations of <20, 20–39, 40–59 and ≥60 ng/ml were significantly different (P = 0.02), with the highest proportion breast cancer-free in the ≥60 ng/ml group (99.3%) and the lowest proportion breast cancer-free in the <20 ng/ml group (96.8%). The proportion with breast cancer was 78% lower for ≥60 vs <20 ng/ml (P = 0.02). Third, multivariate Cox regression revealed that women with 25(OH)D concentrations ≥60 ng/ml had an 80% lower risk of breast cancer than women with concentrations <20 ng/ml (HR = 0.20, P = 0.03), adjusting for age, BMI, smoking status, calcium supplement intake, and study of origin. Conclusions Higher 25(OH)D concentrations were associated with a dose-response decrease in breast cancer risk with concentrations ≥60 ng/ml being most protective.


Citations (61)


... Moreover, the activated VDR opposes a key downstream effect of β-catenin by promoting proteasomal degradation of c-Myc (Salehi et al., 2019;Zuo et al. 2020). Consistent with a protective effect of vitamin D in CRC, regions with greater exposure to UV light tend to have lower risk for this cancer (Haidari et al., 2019;Purushothaman et al., 2021). Epidemiological studies examining the association between plasma levels of calcidiol (25-hydroxyvitamin D) and subsequent risk for colonic adenomas or CRC suggest that low, borderline-deficient levels correlate with increased risk, but that a threshold is reached (at 100 nmol/L) such that high levels do not appear to be more protective than moderate levels considered adequate (McCullough et al. 2019). ...

Reference:

Targeting beta-catenin signaling for prevention of colorectal cancer – Nutraceutical, drug, and dietary options
Could age increase the strength of inverse association between ultraviolet B exposure and colorectal cancer?

BMC Public Health

... Due to its production during sun exposure, vitamin D is often referred to as the "sunshine vitamin" [7]. Ultraviolet radiation (UVR) in the 295-400 nm wavelength range is a significant contributor to vitamin D production [8]. However, it is important to note that excessive exposure to UVR can have carcinogenic effects [9]. ...

Insufficient Sun Exposure Has Become a Real Public Health Problem

... The inflammatory potential of the diet, as estimated by the E-DII, has been consistently associated with disease outcomes and mortality (6)(7)(8)(9)(10)(11)(12) . However, there are only few studies that have contributed additional evidence by examining longitudinal changes in the inflammatory potential of diet (13,14,(24)(25)(26) . In the Women's Health Initiative Observational Study where FFQ were repeated among postmenopausal women (aged 50-79 years at baseline), mean E-DII score decreased modestly from -1·14 at baseline to -1·50 at Year 3 representing a transition towards an anti-inflammatory diet (24) . ...

Changes in the Dietary Inflammatory Index Over Time and Cancer Development Within Rural Post-Menopausal Women

Current Developments in Nutrition

... The review finding of the relationship of vitamin D inadequacy with breast malignant growth is steady with the findings of an observational Mediterranean review, where lacking values were related to highgrade breast malignant growth. Another new pooled cohort exhibited that vitamin D values >60ng/ml brought down the gamble of breast malignant growth by eighty per cent contrasted with ladies with values of < 20 ng/ml 18 . ...

Correction: Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study

... However, in the JPHC case-cohort study, premenopausal women in the third quartile of plasma 25(OH)D levels exhibited a lower risk of breast cancer compared with those in the first quartile, while no association was observed among postmenopausal women [21]. Furthermore, a pooled analysis of two RCTs and a prospective cohort of women (with a baseline median 25(OH)D level of 85 nmol/L) found a significant reduction in breast cancer risk for women with 25(OH)D levels > 150 nmol/L compared with those with < 50 nmol/L [52]. In our study, we observed no significant association between vitamin D levels and breast cancer risk, either overall or in subgroup analyses by menopausal status; however, this lack of significance may be due to limited statistical power, particularly for women with 25(OH)D levels above 100 nmol/L, highlighting the need for further investigation. ...

Breast cancer risk markedly lower with serum 25-hydroxyvitamin D concentrations ≥60 vs <20 ng/ml (150 vs 50 nmol/L): Pooled analysis of two randomized trials and a prospective cohort

... Studies have shown that for every 10 ng/mL (25 nmol/L) increase in 25(OH)D concentration, there is a significant risk reduction, with a hazard ratio (HR) of 0.64 (CI = 0.48-0.86) [79]. ...

Plasma 25-hydroxyvitamin D concentration and risk of type 2 diabetes and pre-diabetes: 12-year cohort study

... We did not detect this difference according to race in the smaller group of men. [40] In both women (Pearson's correlation coefficient =0.846, p<0.001) [41] and men ( =0.712, p<0.001), plasma E1 and E2 levels were highly correlated. ...

Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men

... Vitamin D3 (cholecalciferol) is an essential component of human body that regulates calcium metabolism, growth and maturation, deficiency of which leads to the development of osteoporosis, diabetes and hypertension (Norman 2008). Several reports demonstrate its antiproliferative activity against cancer cells (Gorham et al. 2007, Chung et al. 2009, Lappe et al. 2017). D3 plays a significant role in inflammation and immune response (Baeke et al. 2010;Nnoaham and Clarke 2008). ...

Vitamin D Supplementation and Cancer Risk
  • Citing Article
  • July 2017

JAMA The Journal of the American Medical Association

... However, the literature on the relationship between vitamin D levels and kidney stone risk is inconclusive [12]. Some studies have indicated that elevated vitamin D levels may be associated with an increased risk of kidney stones [13][14][15][16], while others have not observed a significant association [17,18]. This inconsistency may be attributed to various factors, including study design, sample selection, and data analysis methods. ...

Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial
  • Citing Article
  • March 2017

JAMA The Journal of the American Medical Association

... Association between serum 25-hydroxyvitamin D concentration and the risk of colorectal cancer errors in the processing or classification of 25(OH)D concentrations [23], small sample sizes, specific study populations, and potential confounding factors could all impact the results, limiting their generalizability and robustness. A prospective study of elderly men aged 70-88 years found no correlation between serum 25(OH)D concentrations and CRC risk, which could be due to their relatively low winter serum 25(OH)D concentrations (mean of 18 ng/ml) compared to the levels typically observed in younger and middle-aged individuals [24]. ...

Dose-response of serum 25-hydroxyvitamin D in association with risk of colorectal cancer: A meta-analysis
  • Citing Article
  • December 2016

The Journal of Steroid Biochemistry and Molecular Biology