Vitamin D and Endometrial Cancer

Kyle J. Norton(Draft Article)
Epidemiological studies foscusing in the level of circulating 25-hydroxyvitamin D (25(OH)D and dietary vitamin D in reduced risk of endometrial cancer have been inconclusive.
The incidence of endometrial cancer among white women are higher in comparison of black women. According to the statistic, the risk of endometrial cancer among women is 1 in 7000. Every year, about 40,000 women in US are diagnosed with the disease. Women who carry certain mutation genes, such as BRCA1 or the BRCA2 are associated to increased risk of endometrial cancer.
Depending to the stage and grade of the cancer, chemotherapy such as Doxorubicin, Cisplatin. Paclitaxel, Carboplatin, Topotecan may be necessary after surgery with certain side effects. Although epidemiological studies focusing the effective of vegetables and fruits in reduced risk and treatment of endometrial cancer with inconclusive results(1)(2)(3)(4), certain Vitamins, through clinical studies have found to be effective in reduced risk and treatment of endometrial cancer with little or no side effect.

Vitamin D is a fat-soluble secosteroids found in small amount in few foods, including salmon, mackerel, sardines and tuna. The vitamin plays an important role in modulation of cellular proliferation, apoptosis induction, tumor growth suppression and promotion in absorption of minerals, including calcium, iron, magnesium, phosphate and zinc.

 A nested case-control study, including 830 cases and 992 controls from 7 cohorts showed that there was no association between 25(OH)D concentration and disease risk, after adjustment for body mass index(1). The analysis of the effect of 25(OH)D and total dietary vitamin D intake used the Cox proportional hazards model, also indiacted no protection against the development of endometrial cancer with intake of vitamin D(1a) and  in an obese animal model, inhibited obesity-induced increase in endometrial lesions but not endometrial cancer risk(1b). But the study of The Cancer Registry of Norway, Institute of Population-based Cancer Research, indicated that a serum level of 25-OHD around 50 nmol/L appears to be a threshold level, lower serum levels of 25-OHD may be associated to cancer due to several mechanisms. including Vitamin D supplementation could retard the disease process or prolong survival time(2)(3). Other in the study of the effects of progesterone, calcitriol, and their combination on immortalized human endometrial epithelial cells and endometrial cancer cells, showed a sgnificant increased levels of circulating 25-hydroxyvitamin D (25(OH)D and  inhibition of cell proliferation through caspase-3 activation and induction of G0-G1 cell-cycle arrest with associated downregulation of cyclins D1 and D3 and p27 induction(4). In the differentiation of serum 25-hydroxyvitamin D (25(OH)D) concentrations with incidence and/or mortality rates for about 20 types of cancer and improved survival rates for eight types of cancer, suggested that  both measurements of serum 25(OH)D concentrations and increasing serum 25(OH)D concentrations  should be considered of those diagnosed with cancer, of that may improved survival rates and reduced disparities(5). The expression of SEMA3B, SEMA3F(secreted proteins that regulate angiogenesis, tumor growth, and metastasis), are found to be lower in women with endometrial cancer, due tothe the loss of SEMAs in contribution to the malignant phenotype of endometrial cancer cells,  72 hours treatment with conbination of progesterone (P4) and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]  showed a a significant upregulation of SEMA3B and SEMA3F and inhibited growth of cancer cells by increasing caspase-3 activity(6).

Taking altogether, without going into reviews, vitamin D and high levels of circulating 25-hydroxyvitamin D (25(OH)D may be associated to reduced risk and treatment of endometrial cancerthrough certain mechanisms such as cell cycle arrest, upregaulation induced apoptic and anti proliferative expessions. Over doses of vitamin D supplement may cause excessive calcium absorption, calcification, Urinary stones etc. please make sure to follow the guideline of the Institute of Medicine of the National Academies.
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References
(1) Circulating 25-hydroxyvitamin D and risk of endometrial cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers by Zeleniuch-Jacquotte A¹, Gallicchio L, Hartmuller V, Helzlsouer KJ, McCullough ML, Setiawan VW, Shu XO, Weinstein SJ, Weiss JM, Arslan AA, De Vivo I, Gao YT, Hayes RB, Henderson BE, Horst RL, Koenig KL, Patel AV, Purdue MP, Snyder K, Steplowski E, Yu K, Zheng W, Hankinson SE.(PubMed)
(1a) Prospective analysis of vitamin D and endometrial cancer risk by Liu JJ¹, Bertrand KA, Karageorgi S, Giovannucci E, Hankinson SE, Rosner B, Maxwell L, Rodriguez G, De Vivo I.(PubMed)
(1b) Dietary vitamin D exposure prevents obesity-induced increase in endometrial cancer in Pten+/- mice by Yu W¹, Cline M, Maxwell LG, Berrigan D, Rodriguez G, Warri A, Hilakivi-Clarke L.(Pubmed)
(2) The Inverse Relationship between 25-Hydroxyvitamin D and Cancer Survival: Discussion of Causation by Robsahm TE¹, Schwartz GG, Tretli S.(PubMed)
(3) Seasonal vitamin D changes and the impact on health risk assessment by Rosecrans R¹, Dohnal JC(PubMed)
(4) Progesterone enhances calcitriol antitumor activity by upregulating vitamin D receptor expression and promoting apoptosis in endometrial cancer cells by Lee LR¹, Teng PN, Nguyen H, Hood BL, Kavandi L, Wang G, Turbov JM, Thaete LG, Hamilton CA, Maxwell GL, Rodriguez GC, Conrads TP, Syed V.(PubMed)
(5) Differences in vitamin D status may account for unexplained disparities in cancer survival rates between African and white Americans by Grant WB, Peiris AN.(PubMed)
(6) Progesterone and 1,25-dihydroxyvitamin D₃ inhibit endometrial cancer cell growth by upregulating semaphorin 3B and semaphorin 3F by Nguyen H¹, Ivanova VS, Kavandi L, Rodriguez GC, Maxwell GL, Syed V.(PubMed)