Vitamin D and Ovarian Cancer

Posted by Chantel Martiromo

Ovarian cancer is defined as a condition of  abnormal ovarian cells growth of ovaries.  It is one of most common cancer in US, according to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States will be diagnosed with ovarian cancer and 13,850 deaths.
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.

1. Serum of vitamin D and genes mutation
Suggestion of epidemiological studies, linking people who live in higher attitude or carry vitamin D receptor VDR rs2228570 and ApaI polymorphism are associated to the incidence of ovarian cancer and related motility rate(1)(2)(3)(4). These may be due to vitamin D deficiency and genes mutation. According to Uniwersytet Mikołaja Kopernika w Toruniu, [1.25(OH)2D3, the active form of vitamin D showed to inhibit cancer cell growth, induced cancer cell maturation, apoptosis, and decreased angiogenesis. People with lower levels of  serum 25-hydroxyvitamin D (25[OH]D) are associated to risk of ovarian cancer development(6)(7), lower overall survival rate and severe deficiency in more aggressive course of ovarian cancer(5). But the Vanderbilt University School of Medicine, in association between circulating 25(OH)D and ovarian cancer risk, in logistic regression models used to estimate odds ratios and 95% confidence intervals among 516 cases and 770 matched controls, do not support an overall association between circulating 25(OH)D and ovarian cancer risk, except possibly among overweight women(8).

The efficacy
Epidemiological studies focusing in vitamin D in reduced risk of ovarian cancer have been inclusive. The study of Brigham and Women's Hospital and Harvard Medical School, in a total of 1,225 incident epithelial ovarian cancer cases (NHS: 970, NHSII: 255) over 4,628,648 person-years of follow-up, indicated no evidence to support intake of vitamin D from food or supplements or predicted 25(OH)D levels are associated to risk of ovarian cancer(9) neither Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D(10), nor vitamin D supplementation(11).  But according to Dr. Holick MF., Improved vitamin D status is associated to decreased risk for developing several deadly cancers including colon, breast, pancreatic and ovarian cancers(12) and Uniwersytet Mikołaja Kopernika w Toruniu, Vitamin D3 supplementation in moderate doses, many be benefits in decreased risk of developing cancer, including ovarian cancer(13). Some researchers suggested that 1,25-Dihydroxyvitamin D3 suppressed telomerase (a an essential enzyme that counteracts the telomere attrition accompanying DNA replication during cell division) expression and decreased in malignant human ovarian tumors as well as human ovarian cancer cell lines through microRNA(short (20-24 nt) non-coding RNAs are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs.)-498(14)(15). In ovarian epithelial cancers (OCa), 1,25-dihydroxyvitamin D(3) (1,25(OH)(2) VD)(3) induced OCa cell apoptosis through down-regulating telomerase(16). Adding to above findings, The study by University of Hawaii Cancer Center suggested that lifetime vitamin D exposure may be inversely associated with risk of ovarian carcinoma(17).

Taking altogether, serum levels of vitamin D and vitamin D may be associated to reduced risk and treatment of  ovarian cancer, through regulation of genes and suppression telomerase expression. 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
(a) Fruit and vegetable consumption and risk of epithelial ovarian cancer: the European Prospective Investigation into Cancer and Nutrition by Schulz M¹, Lahmann PH, Boeing H, Hoffmann K, Allen N, Key TJ, Bingham S, Wirfält E, Berglund G, Lundin E, Hallmans G, Lukanova A, Martínez Garcia C, González CA, Tormo MJ, Quirós JR, Ardanaz E, Larrañaga N, Lund E, Gram IT, Skeie G, Peeters PH, van Gils CH, Bueno-de-Mesquita HB, Büchner FL, Pasanisi P, Galasso R, Palli D, Tumino R, Vineis P, Trichopoulou A, Kalapothaki V, Trichopoulos D, Chang-Claude J, Linseisen J, Boutron-Ruault MC, Touillaud M, Clavel-Chapelon F, Olsen A, Tjønneland A, Overvad K, Tetsche M, Jenab M, Norat T, Kaaks R, Riboli E.(PubMed)
(b) Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies by Koushik A¹, Hunter DJ, Spiegelman D, Anderson KE, Arslan AA, Beeson WL, van den Brandt PA, Buring JE, Cerhan JR, Colditz GA, Fraser GE, Freudenheim JL, Genkinger JM, Goldbohm RA, Hankinson SE, Koenig KL, Larsson SC, Leitzmann M, McCullough ML, Miller AB, Patel A, Rohan TE, Schatzkin A, Smit E, Willett WC, Wolk A, Zhang SM, Smith-Warner SA(PubMed).
(c) Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk by Riboli E¹, Norat T.(PubMed)
(d) Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis by Fairfield KM¹, Hankinson SE, Rosner BA, Hunter DJ, Colditz GA, Willett WC.(PubMed)
(1) Vitamin D receptor is a novel drug target for ovarian cancer treatment by Zhang X¹, Nicosia SV, Bai W.(PubMed)
(2) Systematic review and meta-analysis on vitamin D receptor polymorphisms and cancer risk by Xu Y¹, He B, Pan Y, Deng Q, Sun H, Li R, Gao T, Song G, Wang S.(PubMed)
(3) Vitamin D receptor rs2228570 polymorphism and invasive ovarian carcinoma risk: pooled analysis in five studies within the Ovarian Cancer Association Consortium by Lurie G¹, Wilkens LR, Thompson PJ, Carney ME, Palmieri RT, Pharoah PD, Song H, Hogdall E, Kjaer SK, DiCioccio RA, McGuire V, Whittemore AS, Gayther SA, Gentry-Maharaj A, Menon U, Ramus SJ, Goodman MT; Ovarian Cancer Association Consortium.(PubMed)
(4) Vitamin D receptor FokI, BsmI, ApaI, and TaqI polymorphisms and susceptibility to ovarian cancer: a meta-analysis by Song GG¹, Lee YH.(PubMed)
(5) [The role of vitamin D in the carcinogenesis of breast and ovarian cancer].

[Article in Polish by Walentowicz-Sadłecka M¹, Sadłecki P, Walentowicz P, Grabiec M.(PubMed)

(6) Casting light on 25-hydroxyvitamin D deficiency in ovarian cancer: a study from the NHANES by Bakhru A¹, Mallinger JB, Buckanovich RJ, Griggs JJ.(PubMed)
(7) Serum 25-hydroxyvitamin D and the risk of ovarian cancer by Toriola AT¹, Surcel HM, Agborsangaya C, Grankvist K, Tuohimaa P, Toniolo P, Lukanova A, Pukkala E, Lehtinen M.(PubMed)

(8) Circulating 25-hydroxyvitamin D and risk of epithelial ovarian cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers by Zheng W¹, Danforth KN, Tworoger SS, Goodman MT, Arslan AA, Patel AV, McCullough ML, Weinstein SJ, Kolonel LN, Purdue MP, Shu XO, Snyder K, Steplowski E, Visvanathan K, Yu K, Zeleniuch-Jacquotte A, Gao YT, Hankinson SE, Harvey C, Hayes RB, Henderson BE, Horst RL, Helzlsouer KJ.(PubMed)
(9) Surrogates of long-term vitamin d exposure and ovarian cancer risk in two prospective cohort studies by Prescott J¹, Bertrand KA, Poole EM, Rosner BA, Tworoger SS.(PubMed)
(10) Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of incident ovarian cancer by Tworoger SS¹, Lee IM, Buring JE, Rosner B, Hollis BW, Hankinson SE.(PubMed)
(11) The association of vitamin D supplementation with the risk of cancer in postmenopausal women by Redaniel MT¹, Gardner MP, Martin RM, Jeffreys M.(PubMed)
(12) Vitamin D, sunlight and cancer connection by Holick MF.(PubMed)
(13) [The role of vitamin D in the carcinogenesis of breast and ovarian cancer].

[Article in Polish] by Walentowicz-Sadłecka M¹, Sadłecki P, Walentowicz P, Grabiec M.(PubMed)

(14) MIR498 microRNA 498 [ Homo sapiens (human) ](PubMed)

(15) 1,25-Dihydroxyvitamin D3 suppresses telomerase expression and human cancer growth through microRNA-498 by Kasiappan R¹, Shen Z, Tse AK, Jinwal U, Tang J, Lungchukiet P, Sun Y, Kruk P, Nicosia SV, Zhang X, Bai W.(PubMed) 

(16) Induction of ovarian cancer cell apoptosis by 1,25-dihydroxyvitamin D3 through the down-regulation of telomerase by Jiang F¹, Bao J, Li P, Nicosia SV, Bai W.(PubMed) 

(17) Cataract and ovarian carcinoma: is the vitamin D hypothesis alive? by Lurie G¹, Matsuno RK, Wilkens LR, Thompson PJ, Ollberding NJ, Carney ME, Goodman MT.(PubMed)