Serum Vitamin D and Risk of Breast Cancer within Five Years

O’Brien, Katie M.; Sandler, Dale P.; Taylor, Jack A.; Weinberg, Clarice R.

doi:10.1289/ehp943

Cited by 63 publications

(69 citation statements)

References 55 publications

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“…As discussed previously, the main strengths of our study include prospective collection of serum specimens, detailed covariate information, use of LC/MS to measure 25(OH)D levels (including 3-epi-25(OH)D 3 ), our use of a cohort with higher than average breast cancer risk, and data from a highly motivated and committed cohort of women (19). Most other studies of this topic have relied on either 25(OH)D levels in samples collected after cases’ diagnoses, which may have been altered by the disease or disease-related behavioral changes, or on prospectively collected 25(OH)D levels that might have reflected levels from a time period not relevant to breast cancer risk.…”

Section: Discussionmentioning

confidence: 99%

“…As described previously (19), we used liquid chromatography-mass spectrometry to measure each of three vitamin D metabolites – 25(OH)D 3 , 25(OH)D 2 , and 3-epi-25(OH)D 3 . The concentration sum of these metabolites was used to estimate overall available serum vitamin D. 25(OH)D 3 was the most prevalent metabolite, making up approximately 83% of the total.…”

Section: Methodsmentioning

confidence: 99%

“…In a recent prospective observational study of vitamin D and incident breast cancer, we reported that women with 25(OH)D levels in the highest quartile (>38.0 ng/mL) had a reduced risk of breast cancer over the subsequent 5 years, relative to women with 25(OH)D levels in the lowest quartile (≤24.6 ng/mL; adjusted HR=0.79; CI: 0.63–0.98) (19). The association may be limited to post-menopausal women.…”

Section: Introductionmentioning

confidence: 99%

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Single-Nucleotide Polymorphisms in Vitamin D–Related Genes May Modify Vitamin D–Breast Cancer Associations

O’Brien

Sandler

Kinyamu

et al. 2017

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background We previously observed that high serum 25-hydroxyvitamin D [25(OH)D] (>38.0 ng/mL) was inversely associated with breast cancer. Here, we examined effect modification by single nucleotide polymorphisms (SNPs) in vitamin D-related genes. Methods The Sister Study enrolled 50,884 US women who had a sister with breast cancer, but who had never had breast cancer themselves. Using a case-cohort design, we compared 1,524 women who developed breast cancer within 5 years to 1,810 randomly selected participants. We estimated ratios of hazards ratios (RHRs) for the 25(OH)D-breast cancer association per copy of the minor allele using Cox proportional hazards models. We considered 82 SNPs in 7 vitamin D-related genes (CYP24A1, CYP27B1, CYP2R1, GC, DHCR7/NADSYN1, RXRA, and VDR). We also tested gene-based interactions with 25(OH)D. Results The SNP with the smallest interaction p-value was rs4328262 in VDR (p=0.0008); the 25(OH)D hazard ratio (HR) was 0.92 (95% confidence interval [CI]: 0.68–1.24) among those homozygous for the common allele, and the minor allele was estimated to decrease the HR by 33% per copy (RHR=0.67, 95% confidence interval [CI]=0.53–0.85). Five other VDR SNPs showed evidence of interaction at p<0.05, as did one SNP in CYP2R1 and one in RXRA. As a group, the 82 SNPs showed evidence of multiplicative interaction with 25(OH)D (p=0.04). In gene-based tests, only VDR showed strong evidence of interaction (p=0.04). Conclusions SNPs in vitamin D-related genes may modify the association between serum 25(OH)D and breast cancer. Impact This work strengthens the evidence for protective effects of vitamin D.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Single-Nucleotide Polymorphisms in Vitamin D–Related Genes May Modify Vitamin D–Breast Cancer Associations

O’Brien

Sandler

Kinyamu

et al. 2017

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…The results indicate a positive correlation between longer exposure to the sun and reduced breast cancer mortality [86,87], whereas the collected data indicate mixed results when it comes to the effects of diet or supplementation [88,89]. The higher circulating level of 25(OH)D (i.e., above 38.0 ng/mL) in blood reduced the risk of cancer development over the next five years (HR = 0.79; CI: 0.63-0.98) [90]. Epidemiological studies indicated a positive effect for women with postmenopausal cancers.…”

Section: Breast Cancermentioning

confidence: 99%

“…The polymorphisms that were selected for this study appeared in earlier papers as factors influencing the occurrence of breast cancer [92]. The polymorphism rs10877012 in another study was taken into account, as only polymorphisms with MAF below two percent were excluded; a study within this polymorphism showed an interaction with 25(OH)D levels in relation to breast cancer development [90]. As the authors point out, this gene may play a role in the prevention of cancer in individual cases, depending on the amount of UV-B radiation and the content of vitamin D in the diet [85].…”

Section: Breast Cancermentioning

confidence: 99%

Single Nucleotide Polymorphisms in 25-Hydroxyvitamin D3 1-Alpha-Hydroxylase (CYP27B1) Gene: The Risk of Malignant Tumors and Other Chronic Diseases

et al. 2020

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Vitamin D is widely known for its roles in the promotion of apoptosis and differentiation, with simultaneous inhibition of proliferation, inflammation, angiogenesis, invasion, and metastasis. Modern literature lacks complete information on polymorphisms in CYP27B1, the only enzyme capable of vitamin D activation. This review presents gathered data that relate to genetic variants in CYP27B1 gene in correlation to multiple diseases, mostly concerning colorectal, prostate, breast, lung, and pancreatic cancers, as well as on other pathologies, such as non-Hodgkin's lymphoma, oral lichen planus, or multiple sclerosis.

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Vitamin D concentrations and breast cancer incidence among Black/African American and non‐Black Hispanic/Latina women

O’Brien

Harmon

Jackson

et al. 2022

Cancer

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Background Vitamin D may protect against breast cancer. Although Black/African American women and Hispanic/Latina women have lower circulating vitamin D levels than non‐Hispanic White women, few studies have examined the association between vitamin D and breast cancer within these racial/ethnic groups. Methods The vitamin D–breast cancer association was evaluated using a case‐cohort sample of self‐identified Black/African American and non‐Black Hispanic/Latina women participating in the US‐wide Sister Study cohort. Circulating 25‐hydroxyvitamin D (25(OH)D) and 24,25‐dihydroxyvitamin D (24,25(OH)2D) were measured using liquid chromatography‐tandem mass spectrometry in blood samples collected at the baseline from 415 women (290 Black/African American women and 125 non‐Black Hispanic/Latina women) who developed breast cancer. These were compared to concentrations in 1545 women (1084 Black/African American women and 461 Hispanic/Latina women) randomly selected from the cohort. Multivariable‐adjusted Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Over a mean follow‐up of 9.2 years, women with circulating 25(OH)D concentrations above the clinical cut point for deficiency (20.0 ng/mL) had lower breast cancer rates than women with concentrations ≤ 20 ng/mL (HR, 0.79; 95% CI, 0.61‐1.02). The inverse association was strongest among Hispanic/Latina women (HR, 0.52; 95% CI, 0.29‐0.93), with a weaker association observed among Black/African American women (HR, 0.89; 95% CI, 0.68‐1.18; P for heterogeneity = 0.13). There were no clear differences by menopausal status, follow‐up time, estrogen receptor status, or invasiveness. Neither 24,25(OH)2D nor the 24,25(OH)2D to 25(OH)D ratio were independently associated with breast cancer risk. Conclusions This prospective study supports the hypothesis that vitamin D may be protective against breast cancer incidence in women, including non‐Black Hispanic/Latina and Black/African American women. LAY SUMMARY Vitamin D may protect against breast cancer. Although women of color have lower average vitamin D levels than non‐Hispanic White women, few studies have considered the role of race/ethnicity. In a sample of self‐identified Black/African American and Hispanic/Latina women, we observed that vitamin D concentrations measured in blood were inversely associated with breast cancer, particularly among Latinas. These findings indicate that vitamin D may protect women against breast cancer, including those in racial/ethnic groups with low average circulating levels.

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Serum Vitamin D and Risk of Breast Cancer within Five Years

Cited by 63 publications

References 55 publications

Single-Nucleotide Polymorphisms in Vitamin D–Related Genes May Modify Vitamin D–Breast Cancer Associations

Single-Nucleotide Polymorphisms in Vitamin D–Related Genes May Modify Vitamin D–Breast Cancer Associations

Single Nucleotide Polymorphisms in 25-Hydroxyvitamin D3 1-Alpha-Hydroxylase (CYP27B1) Gene: The Risk of Malignant Tumors and Other Chronic Diseases

Vitamin D concentrations and breast cancer incidence among Black/African American and non‐Black Hispanic/Latina women

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