Abstract
Breast cancer (BC) is a common cancer among women, especially in developing countries. Circulating serum 25-hydroxyvitamin D [25(OH)D] is the key factor that regulates tissue synthesis of the active form 1,25-dihydroxyvitamin D [1,25(OH)2D]. 1,25(OH)2D has anticarcinogenic properties against breast cancer via binding to vitamin D receptors (VDRs). One of the common VDRs gene polymorphism which is located at the 3′ end of VDR gene is the Bsm-I gene polymorphism (rs1544410). Certain VDRs polymorphisms are associated with obesity and show relation to breast cancer risk. The current study was conducted on 60 breast cancer females and 30 healthy control subjects of matched age. Total serum 25(OH) vitamin D was measured using enzyme-linked immunosorbent assay (ELISA) technique. Vitamin D receptor VDR–Bsm1 gene polymorphism was assessed by PCR/RFLP method. Levels of 25(OH) vitamin D were significantly decreased in total, overweight, and obese BC patients in comparison to control group (p = 0.002, <0.001, <0.001, respectively). Regarding Bsm-1 polymorphism, no significant differences were observed between BC patients and control subjects with no risk to develop BC. Bsm-1 gene polymorphism is not associated with breast cancer risk and this result is not affected by increased BMI. A protective effect is observed for [25(OH)D] and ionized calcium levels against BC development.
Similar content being viewed by others
References
Abd-Elsalam EA, Ismaeil NA, Abd-Alsalam HS (2015) Vitamin D receptor gene polymorphisms and breast cancer risk among postmenopausal Egyptian women. Tumor Biol 36(8):6425–6431
Bae JM, Kim EH (2015) Hormone replacement therapy and risk of breast cancer in Korean women: a quantitative systematic review. J Prev Med Public Health 48(5):225–230
Bikle DD (2010) Vitamin. D and the skin Journal of bone and mineral metabolism 28(2):117–130
Cross BM, Breitwieser GE, Reinhardt TA, Rao R (2014) Cellular calcium dynamics in lactation and breast cancer: from physiology to pathology. Am J Phys Cell Phys 306(6):C515–C526
Du Y, Hu L, Kong F, Pan Y (2014) Lack of association between vitamin D receptor gene BsmI polymorphism and breast cancer risk: an updated meta-analysis involving 23,020 subjects. Tumor Biol 35(3):2087–2093
El Moneim NA, Hewala TI, Rashad M, El-Sayed Y, Abu-Samra N, Anwar M (2015) The role of serum 25-hydroxyvitamin D, ionized calcium and phosphorus in breast cancer females: a case-control study. Int J Basic Appl Sci 4(2):228–237
Fedirko V, Torres-Mejía G, Ortega-Olvera C, Biessy C, Angeles-Llerenas A, Lazcano-Ponce E, Saldaña-Quiroz VA, Romieu I (2012) Serum 25-hydroxyvitamin D and risk of breast cancer: results of a large population-based case–control study in Mexican women. Cancer Causes Control 23(7):1149–1162
Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, MacIntyre MF et al (2015) The global burden of cancer 2013. JAMA Oncol 1(4):505–527
Hauner D, Hauner H (2014) Metabolic syndrome and breast cancer: is there a link? Breast Care 9(4):277–281
Khan MI, Bielecka ZF, Najm MZ, Bartnik E, Czarnecki JS, Czarnecka AM, Szczylik C (2014) Vitamin D receptor gene polymorphisms in breast and renal cancer: current state and future approaches (review). Int J Oncol 44(2):349–363
Li X, Huo X, Li W, Yang Q, Wang Y, Kang X (2014) The role of the rs1544410 polymorphism of vitamin D receptor gene in breast cancer susceptibility. Cell Biochem Biophys 70(3):1951–1956
Mahfoudh W, Bouaouina N, Ahmed SB, Gabbouj S, Shan J, Mathew R, Uhrhammer N, Bignon YJ, Troudi W, Elgaaied AB, Hassen E, Chouchane L (2012) Hereditary breast cancer in middle eastern and north African (MENA) populations: identification of novel, recurrent and founder BRCA1 mutations in the Tunisian population. Mol Biol Rep 39(2):1037–1046
Martínez ME, Pond E, Wertheim BC, Nodora JN, Jacobs ET, Bondy M, Daneri-Navarro A et al (2013) Association between parity and obesity in Mexican and Mexican–American women: findings from the Ella Binational breast cancer study. J Immigr Minor Health 15(2):234–243
Misotti AM, Gnagnarella P (2013) Vitamin supplement consumption and breast cancer risk: a review. Ecancermedicalscience 7:365
Morton ML, Thompson CL (2013) Decreasing 25-hydroxy-vitamin D levels account for portion of effect of increasing body mass index on breast cancer mortality. Mol Nutr Food Res 57(2):260–266
Narvaez CJ, Matthews D, LaPorta E, Simmons KM, Beaudin S, Welsh J (2014) The impact of vitamin D in breast cancer: genomics, pathways, metabolism. Front Physiol 5:213
Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C et al (2014) Global, regional and national prevalence of overweight and obesity in children and adults 1980-2013: a systematic analysis. Lancet 384(9945):766–781
Nickels S, Truong T, Hein R, Stevens K, Buck K, Behrens S, Eilber U et al (2013) Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors. PLoS Genet 9(3):e1003284
Rashid MU, Muzaffar M, Khan FA, Kabisch M, Muhammad N, Faiz S, Loya A, Hamann U (2015) Association between the Bsm I polymorphism in the vitamin D receptor Gene and Breast cancer risk: results from a Pakistani case-control study. PLoS One 10(10):e0141562
Rollison DE, Cole AL, Tung KH, Slattery ML, Baumgartner KB, Byers T, Wolff RK, Giuliano AR (2012) Vitamin D intake, vitamin D receptor polymorphisms, and breast cancer risk among women living in the southwestern US. Breast Cancer Res Treat 132(2):683–691
Sambrook J, Fitsch E, Maniatis T (1989) Molecular cloning a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor
Scarmo S, Afanasyeva Y, Lenner P, Koenig KL, Horst RL, Clendenen TV et al (2013) Circulating levels of 25-hydroxyvitamin D and risk of breast cancer: a nested case-control study. Breast Cancer Res 15(1):R15
Schneider AP 2nd, Zainer CM, Kubat CK, Mullen NK, Windisch AK (2014) The breast cancer epidemic: 10 facts. The Linacre Quarterly 81(3):244–277
Shamsi U, Khan S, Usman S, Soomro S, Azam I (2013) A multicenter matched case control study of breast cancer risk factors among women in Karachi, Pakistan. Asian Pac J Cancer Prev 14(1):183–188
Shanmugalingam T, Crawley D, Bosco C, Melvin J, Rohrmann S, Chowdhury S, Holmberg L, Hemelrijck MV (2014) Obesity and cancer: the role of vitamin D. BioMedCentral cancer 14:712–725
Shao T, Klein P, Grossbard ML (2012) Vitamin D and breast cancer. Oncologist 17(1):36–45
Simpson ER, Brown KA (2013) Minireview: obesity and breast cancer: a tale of inflammation and dysregulated metabolism. Mol Endocrinol 27(5):715–725
Tazhibi M, Dehghani M, Babazadeh S, Makkarian F, Tabatabaeian M, Sadeghi M, Rezaei P, Faghihi M (2014) Hormonal and reproductive risk factors associated with breast cancer in Isfahan patients. J Educ Health Promotion 3:69
Vergne Y, Matta J, Morales L, Vargas W, Alvarez-Garriga C, Bayona M (2013) Breast cancer and DNA repair capacity: association with use of multivitamin and calcium supplements. Integrative medicine (Encinitas, Calif) 12(3):38–46
Wang W, Ingles SA, Torres-Mejía G, Stern MC, Stanczyk FZ, Schwartz GG et al (2014) Genetic variants and non-genetic factors predict circulating vitamin D levels in Hispanic and non-Hispanic white women: the breast cancer health disparities study. Int J Mol Epidemiol Genet 5(1):31–46
Xia X, Chen W, Li J, Chen X, Rui R, Liu C et al (2014) Body mass index and risk of breast cancer: a nonlinear dose-response meta-analysis of prospective studies. Scientific Rep 4:7480
Yang B, Liu S, Yang X, Wang Y, Zhao X, Zheng D et al (2014) Current evidence on the four polymorphisms of VDR and breast cancer risk in Caucasian women. Meta gene 2:41–49
Yoldemir T, Yavuz DG, Anik G, Verimli N, Erenus M (2011) Vitamin D receptor gene polymorphisms in a group of postmenopausal Turkish women: association with bone mineral density. Climacteric 14(3):384–391
Zhang K, Song L (2014) Association between vitamin D receptor gene polymorphisms and breast cancer risk: a meta-analysis of 39 studies. PLoS One 9(4):e96125
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
An informed consent was obtained from all individual participants included in the study, and approval of the local ethics committee of Mansoura University was also obtained with reference cod MS/404.
This work was performed by self financial aid.
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Haikal, N.M.A., El-Hussiny, M.AB., Farouk, O. et al. Bsm1 Gene polymorphism of the vitamin D receptor in breast cancer patients: influence of obesity and relevant drugs. Comp Clin Pathol 26, 127–134 (2017). https://doi.org/10.1007/s00580-016-2354-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00580-016-2354-6