Assessment the effect of vitamin D supplementation on plasma vitamin D levels, inflammation, and oxidative stress biomarkers based on vitamin D receptor genetic variation in breast cancer survivors: a protocol for clinical trial

Abstract Background Both human genes and environmental exposures, due to complex interplay, play important role in the cancer etiology. Vitamin D is associated with a reduced risk of incidence and mortality of several human cancers. This study will aim to investigate the possible effects of individual polymorphisms in vitamin D receptor (VDR) as well as effects of VDR haplotypes on response to vitamin D supplementation in breast cancer survivors. Methods This is an interventional study in which the effects of vitamin D supplementation on plasma vitamin D levels, inflammatory and antioxidant biomarkers and factors associated with cell proliferation, differentiation, damage, and apoptosis will be investigated stratified by variations in VDR genotype. The present study will be conducted on breast cancer survivors referred to the Shohadaye Tajrish hospital and its associated clinics. One hundred ninety-eight breast cancer survivors will receive 4000 IU of vitamin D3 daily for 12 weeks. VDR Fok1, ApaI, TaqI, BsmI, and Cdx-2 genotype will be determined at the end of the study and responses to vitamin D supplements (inflammatory, antioxidant, cell proliferation, differentiation, damage, and apoptosis biomarkers) will be compared between the three subgroups of each VDR polymorphism as well as different VDR haplotype categories. Discussion Genetic variation is a fundamental factor influencing individuals’ divergent responses to diet, nutritional status, metabolic response, and diet-related health disorders. Furthermore, studies of gene and environment interactions will provide a precise and accurate assessments of individuals’ dietary requirements by considering both the genetic and environmental aspects simultaneously. The results of the current study, to some extent, will highlight the discrepancies existing in the findings of different studies regarding vitamin D, VDR, and cancer by considering both the genetic and environmental aspects simultaneously. If responses to vitamin D supplementation could be modified by VDR SNPs, determining the distribution of VDR polymorphisms in both breast cancer survivors and healthy populations will provide a new insight into the vitamin D requirements of individuals to prevent cancer and its related mortality based on their genotypes. Trial registration This trial has been registered on Iranian Registry of Clinical Trials (IRCT) under the identification code: IRCT2017091736244N1, registration date: 2017-11-10, http://www.irct.ir/trial/27153

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Prospective change in 25-OH vitamin D levels over long-term follow-up and health outcomes in breast cancer survivors.

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.15_suppl.6111 ◽

2010 ◽

Vol 28 (15_suppl) ◽

pp. 6111-6111

Author(s):

S. K. Taylor ◽

M. Ennis ◽

N. S. Hood ◽

M. Graham ◽

K. I. Pritchard ◽

...

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Health Outcomes ◽

Cancer Survivors ◽

Breast Cancer Survivors ◽

Vitamin D Levels ◽

Long Term Follow Up ◽

25 Oh Vitamin D

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Clinically sufficient vitamin D levels at breast cancer diagnosis and survival outcomes in a prospective cohort of 3,995 patients after a median follow-up of 10 years.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.10510 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 10510-10510

Author(s):

Song Yao ◽

Haiyang Sheng ◽

Marilyn L. Kwan ◽

Qianqian Zhu ◽

Janise M. Roh ◽

...

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Prospective Cohort ◽

Breast Cancer Survivors ◽

Breast Cancer Diagnosis ◽

Vitamin D Supplementation ◽

Stage Disease ◽

Vitamin D Levels ◽

Sufficient Vitamin

10510 Background: There have been suggestive findings for better cancer survival with vitamin D supplementation in the recent VITAL trial. The findings are consistent with meta-analyses based on earlier randomized trials testing daily supplement vitamin D intake. As there is no ongoing or planned randomized trial of vitamin D supplementation in sight for women after breast cancer diagnosis, we evaluated relationships between serum levels of vitamin D and breast cancer outcomes in a large prospective cohort of breast cancer survivors. Methods: We measured 25-hydroxyvitamin D (25OHD) levels in serum samples collected at the time of diagnosis from 3,995 women with incident breast cancer enrolled in the Pathways Study, a large prospective cohort established in 2006 at Kaiser Permanente Northern California with active follow-up (FU). Potential determinants of 25OHD levels, including a polygenic score, were examined. Vitamin D levels were categorized based on clinical cutoffs as deficient ( < 20 ng/ml), insufficient (20 to < 30 ng/ml), or sufficient (≥30 ng/ml). These levels were then evaluated in relation to overall survival (OS), breast cancer-specific survival (BCSS), recurrence-free survival (RFS), and invasive disease-free survival (IDFS). Cox proportional hazards models were adjusted for non-clinical, clinical, and treatment factors and were further stratified by stage, estrogen receptor (ER) status, and body mass index (BMI). Results: Vitamin D supplement use, lower BMI, and self-reported white race were the strongest determinants of higher 25OHD levels. The polygenic score was significantly associated with 25OHD levels but explained only 0.3% of the variance. The median FU was 9.6 years (range: 0.3-13). Compared to those with deficient vitamin D levels, patients with sufficient levels had significantly better survival outcomes, which remained after controlling for various covariates (OS: HR [95% CI] = 0.73 [0.58-0.91]; BCSS: HR = 0.78 [0.56-1.09]; RFS: HR = 0.79 [0.65-0.97]; IDFS: HR = 0.82 [0.68-0.99]). Associations were similar by ER status, but stronger among patients with more advanced stage disease and those with under-weight or normal BMI. Black patients had the lowest 25OHD levels, which contributed to their poorer survival compared to white patients. Adding 25OHD levels to the Cox model of OS lowered the HR associated with Black vs. white race from 2.03 (1.57-2.62) to 1.79 (1.37-2.32). Conclusions: Sufficient vitamin D levels at the time of diagnosis were associated with improved breast cancer prognosis. Consistent with results from randomized trials, our findings from a large observational cohort of breast cancer survivors with long FU provide the strongest evidence to date for maintaining sufficient vitamin D levels in breast cancer patients, including among Black women and those with more advanced stage disease.

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Serum and Gene Expression Profile of Cytokines Following Combination of Yoga Training and Vitamin D Supplementation in Breast Cancer Survivors

10.21203/rs.3.rs-612814/v1 ◽

2021 ◽

Author(s):

Mehdi Naderi ◽

Hajar Kordestani ◽

Zahra Sahebi ◽

Vahid Khedmati-zareh ◽

Sadegh Amani-Shalamzari ◽

...

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Cancer Survivors ◽

Breast Cancer Survivors ◽

Handgrip Strength ◽

Interleukin 10 ◽

Vitamin D Supplementation ◽

High Dose ◽

Fat Percentage ◽

Tnf Α

Abstract Background This study aimed to examine the effect of a combination of yoga training with high vitamin D dose supplementation on expression and systemic levels of inflammatory cytokines and psychophysical status of breast cancer survivors. Methods Thirty volunteered breast cancer survivors (48 ± 8 yrs.) were randomly allocated to a high dose (4000 IU) of vitamin D supplementation (HD) group (n = 10), yoga with a high dose of vitamin D (YHD) group (n = 10), and yoga with a low dose (2000 IU) of vitamin D (YLD) group (n = 10). Participants performed the Hatha yoga style for 12 weeks, twice a week. Blood samples, quality of life (Qol) questionnaire, and physical performance tests were taken before and after the intervention Results Body fat percentage (ηp2 = 0.36), handgrip strength (ηp2 = 0.41), and Qol indicators include global health (ηp2 = 0.54), functional scales (ηp2 = 0.49), and symptoms scales (ηp2 = 0.50) were significantly improved in the both YHD and YLD groups compared to the HD group (p < 0.05). Also, interleukin-10 (IL-10) levels were markedly increased in the Y-HVD group compared to the Y-LVD and HVD groups. Moreover, there were significant decreases in tumor necrosis factor-α (TNF-α) and interleukin-6 levels in the Y-HVD group after the intervention. The anti-inflammatory index (IL-10/TNF-α) was significantly increased in both the yoga groups (P < 0.05). Conclusion Yoga promotes physical and psychological fitness and, in combination with a high dose of vitamin D, improves the cytokine profile, which can effectively manage the side effects associated with cancer.

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Vitamin D levels in Swiss breast cancer survivors

The Breast ◽

10.1016/s0960-9776(17)30182-0 ◽

2017 ◽

Vol 32 ◽

pp. S51 ◽

Cited By ~ 1

Author(s):

M. Baumann ◽

S. Dani ◽

D. Dietrich ◽

A. Hochstrasser ◽

M.T. Mark ◽

...

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Cancer Survivors ◽

Breast Cancer Survivors ◽

Vitamin D Levels

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174P Better survival associated with successful vitamin D supplementation in non-metastatic breast cancer survivors

Annals of Oncology ◽

10.1016/j.annonc.2021.08.455 ◽

2021 ◽

Vol 32 ◽

pp. S435

Author(s):

E. Isbilen ◽

T. Kus ◽

H. Yesil Cinkir ◽

G. Aktas ◽

A. Buyukbebeci

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Metastatic Breast Cancer ◽

Cancer Survivors ◽

Breast Cancer Survivors ◽

Metastatic Breast ◽

Vitamin D Supplementation

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Vitamin D levels in Swiss breast cancer survivors

Swiss Medical Weekly ◽

10.4414/smw.2018.14576 ◽

2018 ◽

Vol 148 (34) ◽

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Cancer Survivors ◽

Breast Cancer Survivors ◽

Vitamin D Levels

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The high dose of vitamin D supplementation combined with yoga training improve the leukocytes cell survival-related gene expression in breast cancer survivors

Nutrition & Metabolism ◽

10.1186/s12986-021-00607-7 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Vahid Khedmati Zare ◽

Maedeh Javadi ◽

Sadegh Amani-shalamzari ◽

Mojtaba Kaviani

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Vitamin D ◽

Cancer Survivors ◽

Cell Survival ◽

Breast Cancer Survivors ◽

Vitamin D Supplementation ◽

High Dose ◽

Related Gene ◽

Fat Percentage

Abstract Background This study aimed to examine the effect of yoga training combined with vitamin D supplementation on the expression of survival-related genes in leukocytes and psycho-physical status in breast cancer survivors. Methods Thirty breast cancer survivor women (age, 48 ± 8 yrs) were randomly assigned into three groups: high dose (4000 IU) of vitamin D supplementation (HD) (n = 10); yoga training with a high dose of vitamin D (Y + HD); (n = 10); yoga training with a low dose (2000 IU) of vitamin D (Y + LD) (n = 10). Participants performed the Hatha yoga style twice a week. Blood samples and a battery of psychological and physical tests were taken before and after the completion of interventions. Expression of p53, NF-κB, Bcl2, and Bax genes was measured in leukocytes. Results Body fat percentage (ηp2 = 0.36), shoulder flexibility (ηp2 = 0.38), Rockport walk tests (ηp2 = 0.49), and anxiety (ηp2 = 0.52) were significantly improved in both the Y + HD and Y + LD groups compared to the HD group (p < 0.05). P53 was significantly over-expressed in the Y + HD group while Bcl2 upregulated in both the Y + HD and Y + LD groups. NF-κB and Bax expression downregulated in all groups but were not statistically significant. Conclusion yoga training combined with low and high doses of VD improved physical fitness and psychological measures while only in combination with a high dose of VD positively modified the leukocytes cell survival-related gene expression.

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