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Published in: Journal of Ovarian Research 1/2013

Open Access 01-12-2013 | Research

Vitamin D and VDR gene polymorphism (FokI) in epithelial ovarian cancer in Indian population

Authors: Sudhesna Mohapatra, Alpana Saxena, Gauri Gandhi, Bidhan Chandra Koner, Prakash Chandra Ray

Published in: Journal of Ovarian Research | Issue 1/2013

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Abstract

Introduction

Vitamin D deficiency and vitamin D receptor (VDR) gene polymorphism, FokI, is reported to increase the risk of many cancers. Role of vitamin D and its receptor polymorphisms in ovarian cancer has not been clearly defined.

Objective

To study the levels of serum vitamin D and occurrence of vitamin D receptor gene polymorphism (FokI) in cases of ovarian cancer.

Material and methods

FokI genotyping was done by PCR-RFLP technique and vitamin D levels were estimated by chemiluminescence immunoassay.

Results

Serum vitamin D levels were significantly (p < 0.03) lower in ovarian cancer cases as compared to controls. The homozygous (TT) and heterozygous (CT) genotype predispose to the development of ovarian cancer in Indian population (OR: 2.37, 95% CI: 1.04-5.44) as compared to the homozygous (CC) genotype. Vitamin D deficiency and VDR gene polymorphism (FokI) act non-synergistically (p value < 0.4).

Conclusion

Low blood levels of vitamin D and VDR receptor polymorphism (FokI) might be a risk factor for the development of ovarian cancer. Other novel ligands of vitamin D receptor might be responsible for the non-synergistic effect.
Appendix
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Literature
1.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin 2005,55(2):74–108. 10.3322/canjclin.55.2.74PubMedCrossRef Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin 2005,55(2):74–108. 10.3322/canjclin.55.2.74PubMedCrossRef
3.
go back to reference Grant WB: Lower vitamin-D production from solar ultraviolet-B irradiance may explain some differences in cancer survival rates. J Nat Med Assoc 2006,98(3):357–364. Grant WB: Lower vitamin-D production from solar ultraviolet-B irradiance may explain some differences in cancer survival rates. J Nat Med Assoc 2006,98(3):357–364.
4.
go back to reference Jenab M, Bueno-De-Mesquita HB, Ferrari P, Van Duijnhoven FJ, Norat T, Pischon T, Jansen EH, Slimani N, Byrnes G, Rinaldi S, Tjønneland A, Olsen A, Overvad K, Boutron-Ruault MC, Clavel-Chapelon F, Morois S, Kaaks R, Linseisen J, Boeing H, Bergmann MM, Trichopoulou A, Misirli G, Trichopoulos D, Berrino F, Vineis P, Panico S, Palli D, Tumino R, Ros M, Van Gils CH: Diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations: a nested case–control study. BMJ 2010, 340: B5500. 10.1136/bmj.b5500PubMedCentralPubMedCrossRef Jenab M, Bueno-De-Mesquita HB, Ferrari P, Van Duijnhoven FJ, Norat T, Pischon T, Jansen EH, Slimani N, Byrnes G, Rinaldi S, Tjønneland A, Olsen A, Overvad K, Boutron-Ruault MC, Clavel-Chapelon F, Morois S, Kaaks R, Linseisen J, Boeing H, Bergmann MM, Trichopoulou A, Misirli G, Trichopoulos D, Berrino F, Vineis P, Panico S, Palli D, Tumino R, Ros M, Van Gils CH: Diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations: a nested case–control study. BMJ 2010, 340: B5500. 10.1136/bmj.b5500PubMedCentralPubMedCrossRef
5.
go back to reference Arslan AA, Clendenen TV, Koenig KL, Hultdin J, Enquist K, Agren A, Lukanova A, Sjodin H, Zeleniuch-Jacquotte A, Shore R, Hallmans G, Toniolo P, Lundin E: Circulating vitamin D and risk of epithelial ovarian cancer. J Oncol 2009, 2009: 672492.PubMedCentralPubMedCrossRef Arslan AA, Clendenen TV, Koenig KL, Hultdin J, Enquist K, Agren A, Lukanova A, Sjodin H, Zeleniuch-Jacquotte A, Shore R, Hallmans G, Toniolo P, Lundin E: Circulating vitamin D and risk of epithelial ovarian cancer. J Oncol 2009, 2009: 672492.PubMedCentralPubMedCrossRef
6.
go back to reference Tworoger SS, Lee IM, Buring JE, Rosner B, Hollis BW, Hankinson SE: Plasma 25-hydroxyvitamin D and 1,25-Dihydroxyvitamin D and risk of incident ovarian cancer. Cancer Epidemiol Biomarkers Prev 2007, 16: 783–788. 10.1158/1055-9965.EPI-06-0981PubMedCrossRef Tworoger SS, Lee IM, Buring JE, Rosner B, Hollis BW, Hankinson SE: Plasma 25-hydroxyvitamin D and 1,25-Dihydroxyvitamin D and risk of incident ovarian cancer. Cancer Epidemiol Biomarkers Prev 2007, 16: 783–788. 10.1158/1055-9965.EPI-06-0981PubMedCrossRef
7.
go back to reference Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP: Genetics and biology of vitamin D receptor polymorphisms. Gene 2004,338(2):143–156. 10.1016/j.gene.2004.05.014PubMedCrossRef Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP: Genetics and biology of vitamin D receptor polymorphisms. Gene 2004,338(2):143–156. 10.1016/j.gene.2004.05.014PubMedCrossRef
8.
go back to reference Raimondi S, Johansson H, Maisonneuve P, Gandini S: Review and meta-analysis on vitamin D receptor polymorphisms and cancer risk. Carcinogenesis 2009,30(7):1170–1180. 10.1093/carcin/bgp103PubMedCrossRef Raimondi S, Johansson H, Maisonneuve P, Gandini S: Review and meta-analysis on vitamin D receptor polymorphisms and cancer risk. Carcinogenesis 2009,30(7):1170–1180. 10.1093/carcin/bgp103PubMedCrossRef
9.
go back to reference Köstner K, Denzer N, Müller CS, Klein R, Tilgen W, Reichrath J: The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer: a review of the literature. Anticancer Res 2009,29(9):3511–3536.PubMed Köstner K, Denzer N, Müller CS, Klein R, Tilgen W, Reichrath J: The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer: a review of the literature. Anticancer Res 2009,29(9):3511–3536.PubMed
10.
go back to reference Lurie G, Wilkens LR, Thompson PJ, McDuffie KE, Carney ME, Terada KY, Goodman MT: Vitamin D receptor gene polymorphisms and epithelial ovarian cancer risk. Cancer Epidemiol Biomarkers Prev 2007,16(12):2566–2571. 10.1158/1055-9965.EPI-07-0753PubMedCrossRef Lurie G, Wilkens LR, Thompson PJ, McDuffie KE, Carney ME, Terada KY, Goodman MT: Vitamin D receptor gene polymorphisms and epithelial ovarian cancer risk. Cancer Epidemiol Biomarkers Prev 2007,16(12):2566–2571. 10.1158/1055-9965.EPI-07-0753PubMedCrossRef
11.
go back to reference Clendenen TV, Arslan AA, Koenig KL, Enquist K, Wirgin I, Agren A, Lukanova A, Sjodin H, Zeleniuch-Jacquotte A, Shore RE, Hallmans G, Toniolo P, Lundin E: Vitamin D receptor polymorphisms and risk of epithelial ovarian cancer. Cancer Lett 2008,260(1–2):209–215.PubMedCentralPubMedCrossRef Clendenen TV, Arslan AA, Koenig KL, Enquist K, Wirgin I, Agren A, Lukanova A, Sjodin H, Zeleniuch-Jacquotte A, Shore RE, Hallmans G, Toniolo P, Lundin E: Vitamin D receptor polymorphisms and risk of epithelial ovarian cancer. Cancer Lett 2008,260(1–2):209–215.PubMedCentralPubMedCrossRef
12.
go back to reference Tworoger SS, Gates MA, Lee IM, Buring JE, Titus-Ernstoff L, Cramer D, Hankinson SE: Polymorphisms in the vitamin D receptor and risk of ovarian cancer in four studies. Cancer Res 2009,69(5):1885–1891. 10.1158/0008-5472.CAN-08-3515PubMedCentralPubMedCrossRef Tworoger SS, Gates MA, Lee IM, Buring JE, Titus-Ernstoff L, Cramer D, Hankinson SE: Polymorphisms in the vitamin D receptor and risk of ovarian cancer in four studies. Cancer Res 2009,69(5):1885–1891. 10.1158/0008-5472.CAN-08-3515PubMedCentralPubMedCrossRef
13.
go back to reference Lurie G, 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: Vitamin D receptor rs2228570 polymorphism and invasive ovarian carcinoma risk: Pooled analysis in five studies within the Ovarian Cancer Association Consortium. Int J Cancer 2010,128(4):936–943.CrossRef Lurie G, 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: Vitamin D receptor rs2228570 polymorphism and invasive ovarian carcinoma risk: Pooled analysis in five studies within the Ovarian Cancer Association Consortium. Int J Cancer 2010,128(4):936–943.CrossRef
14.
go back to reference Harris SS, Eccleshall TR, Gross C, DawsonHughes B, Feldman D: The VDR start codon polymorphism (Fok-I) and bone mineral density in premenopausal American Black and White women. J Bone Miner Res 1997, 12: 1043–1048. 10.1359/jbmr.1997.12.7.1043PubMedCrossRef Harris SS, Eccleshall TR, Gross C, DawsonHughes B, Feldman D: The VDR start codon polymorphism (Fok-I) and bone mineral density in premenopausal American Black and White women. J Bone Miner Res 1997, 12: 1043–1048. 10.1359/jbmr.1997.12.7.1043PubMedCrossRef
15.
go back to reference Cortina-Borja M, Smith AD, Combarros O, Lehmann DJ: The synergy factor: a statistic to measure interactions in complex diseases. BMC Res Notes 2009, 2: 105. 10.1186/1756-0500-2-105PubMedCentralPubMedCrossRef Cortina-Borja M, Smith AD, Combarros O, Lehmann DJ: The synergy factor: a statistic to measure interactions in complex diseases. BMC Res Notes 2009, 2: 105. 10.1186/1756-0500-2-105PubMedCentralPubMedCrossRef
16.
go back to reference Webb AR, Engelsen O: Calculated ultraviolet exposure levels for a healthy vitamin D status. Photochem Photobiol 2006, 82: 1697–1703.PubMedCrossRef Webb AR, Engelsen O: Calculated ultraviolet exposure levels for a healthy vitamin D status. Photochem Photobiol 2006, 82: 1697–1703.PubMedCrossRef
17.
go back to reference Grant WB: An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer 2002, 94: 1867–1875. 10.1002/cncr.10427PubMedCrossRef Grant WB: An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer 2002, 94: 1867–1875. 10.1002/cncr.10427PubMedCrossRef
18.
go back to reference Lefkowitz ES, Garland CF: Sunlight, vitamin D, and ovarian cancer mortality rates in U.S. women. Int J Epidemiol 1994, 23: 1133–1136. 10.1093/ije/23.6.1133PubMedCrossRef Lefkowitz ES, Garland CF: Sunlight, vitamin D, and ovarian cancer mortality rates in U.S. women. Int J Epidemiol 1994, 23: 1133–1136. 10.1093/ije/23.6.1133PubMedCrossRef
19.
go back to reference Freedman D, Dosemeci M, McGlynn K: Sunlight and mortality from breast, ovarian, colon, prostate, and non-melanoma skin cancer: a composite death certificate based case–control study. Occup Environ Med 2002, 59: 257–262. 10.1136/oem.59.4.257PubMedCentralPubMedCrossRef Freedman D, Dosemeci M, McGlynn K: Sunlight and mortality from breast, ovarian, colon, prostate, and non-melanoma skin cancer: a composite death certificate based case–control study. Occup Environ Med 2002, 59: 257–262. 10.1136/oem.59.4.257PubMedCentralPubMedCrossRef
20.
go back to reference Grant WB: Does solar ultraviolet irradiation affect cancer mortality rates in China? Asian Pacific J Cancer Prev 2007, 8: 236–242. Grant WB: Does solar ultraviolet irradiation affect cancer mortality rates in China? Asian Pacific J Cancer Prev 2007, 8: 236–242.
21.
go back to reference Mohr SB, Gorham ED, Grant WB, Garland FC: Role of Ultraviolet B Irradiance and Vitamin D in Prevention of Ovarian Cancer. Am J Prev Med 2006,31(6):512–514. 10.1016/j.amepre.2006.08.018PubMedCrossRef Mohr SB, Gorham ED, Grant WB, Garland FC: Role of Ultraviolet B Irradiance and Vitamin D in Prevention of Ovarian Cancer. Am J Prev Med 2006,31(6):512–514. 10.1016/j.amepre.2006.08.018PubMedCrossRef
22.
go back to reference Harinarayan CV, Ramalakshmi T, Prasad UV, Sudhakar D, Srinivasarao PV, Sarma KV, Kumar EG: High prevalence of low dietary calcium, high phytate consumption, and vitamin D deficiency in healthy south Indians. Am J Clin Nutr 2007, 85: 1062–1067.PubMed Harinarayan CV, Ramalakshmi T, Prasad UV, Sudhakar D, Srinivasarao PV, Sarma KV, Kumar EG: High prevalence of low dietary calcium, high phytate consumption, and vitamin D deficiency in healthy south Indians. Am J Clin Nutr 2007, 85: 1062–1067.PubMed
23.
go back to reference Goswami R, Kochupillai N, Gupta N, Goswami D, Singh N, Dudha A: Presence of 25(OH)D deficiency in rural north Indian village despite abundant sunshine. J Assoc Physicians India 2008, 56: 755–757.PubMed Goswami R, Kochupillai N, Gupta N, Goswami D, Singh N, Dudha A: Presence of 25(OH)D deficiency in rural north Indian village despite abundant sunshine. J Assoc Physicians India 2008, 56: 755–757.PubMed
24.
go back to reference Duque G, El Abdaimi K, Macoritto M, Miller MM, Kremer R: Estrogens (E2) regulate expression and response of 1,25-dihydroxyvitamin D3 receptors in bone cells: changes with aging and hormone deprivation. Biochem Biophys Res Commun 2002,299(3):446–454. 10.1016/S0006-291X(02)02657-8PubMedCrossRef Duque G, El Abdaimi K, Macoritto M, Miller MM, Kremer R: Estrogens (E2) regulate expression and response of 1,25-dihydroxyvitamin D3 receptors in bone cells: changes with aging and hormone deprivation. Biochem Biophys Res Commun 2002,299(3):446–454. 10.1016/S0006-291X(02)02657-8PubMedCrossRef
25.
go back to reference Whitfield GK, Remus LS, Jurutka PW, Zitzer H, Oza AK, Dang HT, Haussler CA, Galligan MA, Thatcher ML, Encinas Dominguez C, Haussler MR: Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Mol Cell Endocrinol 2001, 177: 145–159. 10.1016/S0303-7207(01)00406-3PubMedCrossRef Whitfield GK, Remus LS, Jurutka PW, Zitzer H, Oza AK, Dang HT, Haussler CA, Galligan MA, Thatcher ML, Encinas Dominguez C, Haussler MR: Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Mol Cell Endocrinol 2001, 177: 145–159. 10.1016/S0303-7207(01)00406-3PubMedCrossRef
26.
go back to reference Zmuda JM, Cauley JA, Ferrell RE: Molecular epidemiology of vitamin D receptor gene variants. Epidemiol Rev 2000,22(2):203–217. 10.1093/oxfordjournals.epirev.a018033PubMedCrossRef Zmuda JM, Cauley JA, Ferrell RE: Molecular epidemiology of vitamin D receptor gene variants. Epidemiol Rev 2000,22(2):203–217. 10.1093/oxfordjournals.epirev.a018033PubMedCrossRef
27.
go back to reference Arai H, Miyamoto K, Taketani Y, Yamamoto H, Iemori Y, Morita K, Tonai T, Nishisho T, Mori S, Takeda E: A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women. J Bone Miner Res 1997, 12: 915–921. 10.1359/jbmr.1997.12.6.915PubMedCrossRef Arai H, Miyamoto K, Taketani Y, Yamamoto H, Iemori Y, Morita K, Tonai T, Nishisho T, Mori S, Takeda E: A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women. J Bone Miner Res 1997, 12: 915–921. 10.1359/jbmr.1997.12.6.915PubMedCrossRef
28.
go back to reference Alimirah F, Peng X, Murillo G, Mehta RG: Functional significance of vitamin D receptor FokI polymorphism in human breast cancer cells. PLoS One 2011,6(1):e16024. 10.1371/journal.pone.0016024PubMedCentralPubMedCrossRef Alimirah F, Peng X, Murillo G, Mehta RG: Functional significance of vitamin D receptor FokI polymorphism in human breast cancer cells. PLoS One 2011,6(1):e16024. 10.1371/journal.pone.0016024PubMedCentralPubMedCrossRef
29.
go back to reference Bartik L, Whitfield GK, Kaczmarska M, Lowmiller CL, Moffet EW, Furmick JK, Hernandez Z, Haussler CA, Haussler MR, Jurutka PW: Curcumin: a novel nutritionally derived ligand of the vitamin D receptor with implications for colon cancer chemoprevention. J Nutr Biochem 2010,21(12):1153–1161. 10.1016/j.jnutbio.2009.09.012PubMedCentralPubMedCrossRef Bartik L, Whitfield GK, Kaczmarska M, Lowmiller CL, Moffet EW, Furmick JK, Hernandez Z, Haussler CA, Haussler MR, Jurutka PW: Curcumin: a novel nutritionally derived ligand of the vitamin D receptor with implications for colon cancer chemoprevention. J Nutr Biochem 2010,21(12):1153–1161. 10.1016/j.jnutbio.2009.09.012PubMedCentralPubMedCrossRef
30.
go back to reference Egan JB, Thompson PA, Vitanov MV, Bartik L, Jacobs ET, Haussler MR, Gerner EW, Jurutka PW: Vitamin D receptor ligands, adenomatous polyposis coli, and the vitamin D receptor FokI polymorphism collectively modulate beta-catenin activity in colon cancer cells. Mol Carcinog 2010,49(4):337–352.PubMedCentralPubMed Egan JB, Thompson PA, Vitanov MV, Bartik L, Jacobs ET, Haussler MR, Gerner EW, Jurutka PW: Vitamin D receptor ligands, adenomatous polyposis coli, and the vitamin D receptor FokI polymorphism collectively modulate beta-catenin activity in colon cancer cells. Mol Carcinog 2010,49(4):337–352.PubMedCentralPubMed
31.
go back to reference Rachez C, Suldan Z, Ward J: A novel protein complex that interacts with the vitamin D3 receptor in a ligand-dependent manner and enhances vitamin D receptor transactivation in a cell-free system. Genes Dev 1998, 12: 1787–1800. 10.1101/gad.12.12.1787PubMedCentralPubMedCrossRef Rachez C, Suldan Z, Ward J: A novel protein complex that interacts with the vitamin D3 receptor in a ligand-dependent manner and enhances vitamin D receptor transactivation in a cell-free system. Genes Dev 1998, 12: 1787–1800. 10.1101/gad.12.12.1787PubMedCentralPubMedCrossRef
Metadata
Title
Vitamin D and VDR gene polymorphism (FokI) in epithelial ovarian cancer in Indian population
Authors
Sudhesna Mohapatra
Alpana Saxena
Gauri Gandhi
Bidhan Chandra Koner
Prakash Chandra Ray
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2013
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/1757-2215-6-37

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