Vitamin A and Endometrial Cancer

 Kyle J. Norton

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 A is a general term of Vitamin A Retinol, retinal, beta-carotene, alpha-carotene, gamma-carotene, and beta-cryptoxanthin best known for its functions for vision health and antioxidant scavenger and essential for growth and differentiation of a number of cells and tissues.
Recommended intakes of vitamin A, according to  the Institute of Medicine of the National Academies (formerly National Academy of Sciences) is 600 µg daily as extremely high doses (>9000 mg) can be toxicity as causes of dry, scaly skin, fatigue, nausea, loss of appetite, bone and joint pains, headaches, etc.
Epidemiological studies, linking vitamin A in reduced risk of endometrial cancer have been inclusive.
1. Retinols
 The Istituto di Ricerche Farmacologiche Mario Negr study in dietary intake of carotenoids and retinol showed no association of retinols in reduced risk of endometrial cancer(5). In the Ishikawa endometrial cancer cell line, Retinoic acid is a metabolite of Retinol inhibited cell proliferation and the expression of RAR(retinoic acid receptor) alpha, RAR beta, and RAR gamma in the Ishikawa endometrial cancer cell line(6). the University Feinberg School of Medicine study in assessing the roles of RA and the RA agonist (AM580) in the growth of endometrial cancer cells, found that both RA and AM580 markedly inhibited endometrial cancer cell proliferation(7). Fenofibrate, an agonist of PPAR-alpha, potentiated by retinoic acid inhibited G1/S phase progression of endometrial cells through the cell cycle arrest(8). In endometrial carcinoma cells line (RL 95-2), RAs exerted its inhibitory effect on the growth of RL 95-2 cells through the estrogen pathway in estrogen-responsive endometrial cancer cells(9) or by interfering with the epidermal growth factor receptor (EGF-R) signaling pathway(10).

2. Carotenoids(beta-carotene, alpha-carotene, gamma-carotene and beta-cryptoxanthin)
Carotenoids, plant pigments, converted to vitamin A after intake, play an important role in prevention and treatment of some diseases through it antioxidant effects. The Brigham and Women's Hospital and Harvard Medical School, in the study of antioxidants intake and risk of endometrial cancer, found no association between intakes of vitamins A, C, E or carotenoids from foods or supplements and cancer risk(11). In a dose-response meta-analysis, intakes of beta-carotene is associated to an inverse risk of endometrial cancer(12). the Medical University of Białystok study in the study suggested that endometrioid adenocarcinoma may be associated to certain enzymatic defects in carotenoid metabolism in the course of the neoplastic process or some metabolic modifications(13). The population-based case-control study in Shanghai, China of 1,204 newly diagnosed endometrial cancer cases and 1,212 age frequency-matched controls, indicated that dietary macronutrients with endometrial cancer associated to cancer risk may depend on the sources, dietary retinol, beta-carotene may decrease the risk of endometrial cancer(14)(15)

Taking altogether, without going into reviews, vitamin A may be associated to reduced risk and treatment of endometrial cancer through inhibition of cell cycle progression, modification of cells differentiated mechanisms. Overdoses can lead to toxic symptoms. Please make sure you follow the guideline of the Institute of Medicine of the National Academies.

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References
(1) Conference on "Multidisciplinary approaches to nutritional problems". Symposium on "Nutrition and health". Cruciferous vegetable intake and the risk of human cancer: epidemiological evidence BY Kim MK, Park JH(PubMed)
(2) Epidemiological studies on brassica vegetables and cancer risk by Verhoeven DT, Goldbohm RA, van Poppel G, Verhagen H, van den Brandt PA(PubMed)
(3) Brassica vegetables and cancer prevention. Epidemiology and mechanisms by van Poppel G, Verhoeven DT, Verhagen H, Goldbohm RA.(PubMed)
(4) Fruits and vegetables and endometrial cancer risk: a systematic literature review and meta-analysis by Bandera EV, Kushi LH, Moore DF, Gifkins DM, McCullough ML(PubMed)
(5) Dietary intake of carotenoids and retinol and endometrial cancer risk in an Italian case-control study by Pelucchi C¹, Dal Maso L, Montella M, Parpinel M, Negri E, Talamini R, Giudice A, Franceschi S, La Vecchia C.(PubMed)
(6) Expression of retinoic acid receptors in human endometrial carcinoma by Tanabe K¹, Utsunomiya H, Tamura M, Niikura H, Takano T, Yoshinaga K, Nagase S, Suzuki T, Ito K, Matsumoto M, Hayashi S, Yaegashi N(PubMed)
(7) Retinoic acid inhibits endometrial cancer cell growth via multiple genomic mechanisms by Cheng YH¹, Utsunomiya H, Pavone ME, Yin P, Bulun SE(PubMed)
(8) In vitro and in vivo effects of the PPAR-alpha agonists fenofibrate and retinoic acid in endometrial cancer by Saidi SA¹, Holland CM, Charnock-Jones DS, Smith SK(PubMed)
(9) Divergent effects of retinoic acids on the expression of ERalpha and 17beta-hydroxysteroid dehydrogenase type 2 in endometrial carcinoma cells (RL 95-2) by Li XH¹, Li H, Xiao ZJ, Piao YS.(PubMed)
(10) Retinoic acid affects the EGF-R signaling pathway during differentiation induction of human endometrial adenocarcinoma cells by Carter CA¹, Shaw BL(PubMed)
(11) Antioxidant intake and risk of endometrial cancer: results from the Nurses' Health Study by Cui X¹, Rosner B, Willett WC, Hankinson SE(PubMed)
(12) Antioxidant vitamins and the risk of endometrial cancer: a dose-response meta-analysis by Bandera EV¹, Gifkins DM, Moore DF, McCullough ML, Kushi LH.(PubMed)
(13) Dietary carotenoids in normal and pathological tissues of corpus uteri by Czeczuga-Semeniuk E¹, Wołczyński S(PubMed)
(14) Nutritional factors in relation to endometrial cancer: a report from a population-based case-control study in Shanghai, China by Xu WH¹, Dai Q, Xiang YB, Zhao GM, Ruan ZX, Cheng JR, Zheng W, Shu XO.(PubMed)
(15) Intake of selected micronutrients and the risk of endometrial carcinoma by Negri E¹, La Vecchia C, Franceschi S, Levi F, Parazzini F.(PubMed)