Meta-analysis: Serum vitamin D and breast cancer risk
Introduction
Although vitamin D is obtained from diet and dietary supplements, the main source for vitamin D is its production in the skin under the influence of solar ultraviolet B (UV-B) radiation. In 1980, Garland and Garland1 hypothesised that lower levels of vitamin D resulting from much weaker UV-B radiation at higher latitudes may account for the striking geographical pattern of cancer mortality. Partly stimulated by this article, further research in this area has been conducted in observational studies over the past 20 years.2, 3, 4
A number of ecological studies found vitamin D status to increase with decreasing latitude and to parallel the south to north gradient in the incidence of female breast cancer (BC),5, 6, 7, 8, 9 however, results were not consistent, and even inverse associations have being reported from Europe.10, 11 Most epidemiologic studies addressing the association between vitamin D and BC have assessed dietary vitamin D intake, and results have also been inconsistent.12, 13, 14, 15, 16, 17, 18, 19, 20 In recent years, several studies have addressed the association of BC risk and serum 25(OH)D levels representing an integrated measure for vitamin D from diet, dietary supplements and skin production, which has a relatively long half-life in the circulatory system of about 2–3 weeks. By contrast, serum levels of 1,25(OH)2, the active metabolite of vitamin D has only a short half-life and its physiological control depends on many factors other than UV exposure or diet, such as calcium balance and the parathyroid hormone. Hence, only serum 25(OH)D is considered to be a useful marker reflecting the ‘vitamin D status’.21
Combining two studies identified by searching the Medline database for 1966–2006, Garland and colleagues22 performed a pooled analysis regarding the association between serum 25(OH)D and BC risk. They found a 50% lower risk of BC associated with a serum 25(OH)D level ⩾52 ng/ml, compared to ⩽13 ng/ml. Since then, a rapidly increasing number of studies have addressed the association of 25(OH)D with BC risk. Therefore, we aimed to provide an up-to-date systematic review and meta-analyses of observational epidemiological studies investigating the association between serum 25(OH)D levels and BC risk by using methods for comprehensive trend estimation from summarised dose–response data.23
Section snippets
Identification of studies and study selection
A literature search was conducted to identify longitudinal studies, nested case-control studies or case-control studies assessing the association between serum levels of 25(OH)D and BC incidence or mortality. We searched Ovid (Ovid Technologies Inc., New York, 1950 – 18th September 2009), EMBASE (Elsevier, Amsterdam, the Netherlands, 1980 – 24th September 2009) and ISI Web of Knowledge (Thomson Scientific Technical Support, New York, 1945 – 24th September 2009) databases for relevant articles
Identification of studies
A flow diagram of the search process is given in Fig. 1. Total searches yielded 4264 entries. Following removal of 1208 duplicates, 3056 titles and abstracts were assessed and 122 articles appeared to be potentially relevant for inclusion into the review. One hundred and ten articles were excluded for the following reasons: no original articles but editorials, comments, reviews (N = 84), only vitamin D intake reported (N = 13), associations of 25(OH)D with BC not reported/not derivable from
Discussion
Our review and meta-analysis summarising the results of nine studies on the association between serum 25(OH)D and incident BC show ambiguous evidence: while case-control studies with measurement of serum 25(OH)D levels after diagnosis support the hypothesis that serum 25(OH)D levels are inversely associated with BC risk, a statistically significant inverse association remained unconfirmed in nested case-control studies, with measurement of serum 25(OH)D levels from blood taken at baseline of
Conclusions
Despite its limitations, our review and meta-analysis provide the most comprehensive and updated summary of epidemiological evidence to date on the association between serum 25(OH)D and BC risk. While case-control studies with measurement of serum 25(OH)D levels after diagnosis seem to support the hypothesis that serum 25(OH)D levels are inversely associated with BC risk, a statistically significant inverse association remained unconfirmed in nested case-control studies, with measurement of
Conflict of interest statement
None declared.
Acknowledgement
The work of Lu Yin was supported by a scholarship from the German Research Foundation (Deutsche Forschungsgemeinschaft) within the framework of a PhD program (Graduiertenkolleg 793).
References (43)
Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis
Am J Clin Nutr
(2004)- et al.
Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation
Prev Med
(1990) - et al.
Serum vitamin D concentrations among elderly people in Europe
Lancet
(1995) The use and interpretation of assays for vitamin D and its metabolites
J Nutr
(1990)- et al.
Vitamin D and prevention of breast cancer: pooled analysis
J Steroid Biochem Mol Biol
(2007) - et al.
Meta-analysis in clinical trials
Control Clin Trials
(1986) - et al.
Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population
Eur J Cancer
(2005) - et al.
Do sunlight and vitamin D reduce the likelihood of colon cancer?
Int J Epidemiol
(1980) The epidemiology of vitamin D and cancer incidence and mortality: a review (United States)
Cancer Causes Control
(2005)- et al.
What is the dose–response relationship between vitamin D and cancer risk?
Nutr Rev
(2007)
Sunlight and breast cancer incidence in the USSR
Int J Epidemiol
An ecologic study of dietary and solar ultraviolet-B links to breast carcinoma mortality rates
Cancer
Solar ultraviolet-B exposure and cancer incidence and mortality in the United States, 1993–2002
BMC Cancer
A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial
J Clin Endocrinol Metab
Vitamin D deficiency and cancer of the breast: an unprovocative ecological hypothesis
Can J Public Health
Intake of food groups and associated micronutrients in relation to risk of early-stage breast cancer
Int J Cancer
Dietary intake of selected micronutrients and breast-cancer risk
Int J Cancer
Intake of dairy products, calcium, and vitamin d and risk of breast cancer
J Natl Cancer Inst
Dairy, calcium, and vitamin D intake and postmenopausal breast cancer risk in the cancer prevention study II nutrition cohort
Cancer Epidemiol Biomarkers Prev
Dietary vitamin D and calcium intake and premenopausal breast cancer risk in a German case-control study
Nutr Cancer
Cited by (180)
Non-classical effects of vitamin D: Non-bone effects of vitamin D
2021, Annales d'EndocrinologieLower serum 25-hydroxyvitamin D is associated with colorectal and breast cancer, but not overall cancer risk: a 20-year cohort study
2019, Nutrition ResearchCitation Excerpt :A meta-analysis published in 2010 showed that in case–control studies an increase in serum 25(OH)D levels by 50 nmol/L was related to 41% reduction in the risk for breast cancer [15]. However, the association was not significant in nested case–control studies [15], and a further meta-analysis of nested case–control and cohort studies published in 2014 showed only a weak, non-significant association (HR for the highest vs the lowest 25(OH)D levels: 0.92, 95% CI: 0.83–1.02) [16]. The lack of association in most cohort and nested cast control studies could be due to the limited length of follow-up, and the small number of participants with relatively high vitamin D status.
Vitamin D supplementation for prevention of cancer: The D2d cancer outcomes (D2dCA)study
2019, Contemporary Clinical TrialsVitamin D and breast cancer: A systematic review and meta-analysis of observational studies
2019, Clinical Nutrition ESPENCitation Excerpt :However, epidemiologic evidence for a relationship between plasma 25(OH)D and BC incidence and/or prevalence is limited [7]. Several longitudinal studies on serum 25(OH)D and multiple cancer risks have concluded that 25(OH)D concentrations are inversely associated with colorectal cancer incidence [8–12] but not with prostate cancer or BC incidence [10,13–15]. In relation to BC, vitamin D has mixed results when separated by menopausal status.
Unraveling the complex link between vitamin D levels and cancer: A crucial understanding for designing future supplementation approaches
2023, Brazilian Journal of Pharmaceutical Sciences