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Breast Cancer Research
Published in: Breast Cancer Research 2/2012

Open Access 01-04-2012 | Research article

Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study

Authors: Song Yao, Gary Zirpoli, Dana H Bovbjerg, Lina Jandorf, Chi Chen Hong, Hua Zhao, Lara E Sucheston, Li Tang, Michelle Roberts, Gregory Ciupak, Warren Davis, Helena Hwang, Candace S Johnson, Donald L Trump, Susan E McCann, Foluso Ademuyiwa, Karen S Pawlish, Elisa V Bandera, Christine B Ambrosone

Published in: Breast Cancer Research | Issue 2/2012

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Abstract

Introduction

American women of African ancestry (AA) are more likely than European Americans (EA) to have estrogen receptor (ER)-negative breast cancer. 25-hydroxyvitamin D (25OHD) is low in AAs, and was associated with ER-negative tumors in EAs. We hypothesized that racial differences in 25OHD levels, as well as in inherited genetic variations, may contribute, in part, to the differences in tumor characteristics.

Methods

In a case (n = 928)-control (n = 843) study of breast cancer in AA and EA women, we measured serum 25OHD levels in controls and tested associations between risk and tag single nucleotide polymorphisms (SNPs) in VDR, CYP24A1 and CYP27B1, particularly by ER status.

Results

More AAs had severe vitamin D deficiency (< 10 ng/ml) than EAs (34.3% vs 5.9%), with lowest levels among those with the highest African ancestry. Associations for SNPs differed by race. Among AAs, VDR SNP rs2239186, associated with higher serum levels of 25OHD, decreased risk after correction for multiple testing (OR = 0.53, 95% CI = 0.31-0.79, p by permutation = 0.03), but had no effect in EAs. The majority of associations were for ER-negative breast cancer, with seven differential associations between AA and EA women for CYP24A1 (p for interaction < 0.10). SNP rs27622941 was associated with a > twofold increased risk of ER-negative breast cancer among AAs (OR = 2.62, 95% CI = 1.38-4.98), but had no effect in EAs. rs2209314 decreased risk among EAs (OR = 0.38, 95% CI = 0.20-0.73), with no associations in AAs. The increased risk of ER-negative breast cancer in AAs compared to EAs was reduced and became non-significant (OR = 1.20, 95% CI = 0.80-1.79) after adjusting for these two CYP24A1 SNPs.

Conclusions

These data suggest that genetic variants in the vitamin D pathway may be related to the higher prevalence of ER-negative breast cancer in AA women.
Appendix
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Literature
1.
Amend K, Hicks D, Ambrosone CB: Breast cancer in African-American women: differences in tumor biology from European-American women. Cancer Res. 2006, 66: 8327-8330. 10.1158/0008-5472.CAN-06-1927.CrossRefPubMed
2.
Ooi LL, Zhou H, Kalak R, Zheng Y, Conigrave AD, Seibel MJ, Dunstan CR: Vitamin D deficiency promotes human breast cancer growth in a murine model of bone metastasis. Cancer Res. 2010, 70: 1835-1844. 10.1158/0008-5472.CAN-09-3194.CrossRefPubMed
3.
Fumagalli M, Sironi M, Pozzoli U, Ferrer-Admettla A, Pattini L, Nielsen R: Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution. PLoS Genet. 2011, 7: e100235-CrossRef
4.
Yuen AW, Jablonski NG: Vitamin D: in the evolution of human skin colour. Med Hypotheses. 2010, 74: 39-44. 10.1016/j.mehy.2009.08.007.CrossRefPubMed
5.
Jablonski NG: The evolution of human skin and skin color. Ann Rev Anthropol. 2004, 33: 585-623. 10.1146/annurev.anthro.33.070203.143955.CrossRef
6.
Chaplin G, Jablonski NG: Vitamin D and the evolution of human depigmentation. Am J Phys Anthropol. 2009, 139: 451-461. 10.1002/ajpa.21079.CrossRefPubMed
7.
Clemens TL, Adams JS, Henderson SL, Holick MF: Increased skin pigment reduces the capacity of skin to synthesise vitamin D3. Lancet. 1982, 1: 74-76.CrossRefPubMed
8.
Nesby-O'Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC, Allen C, Doughertly C, Gunter EW, Bowman BA: Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr. 2002, 76: 187-192.PubMed
9.
Ginde AA, Liu MC, Camargo CA: Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med. 2009, 169: 626-632. 10.1001/archinternmed.2008.604.CrossRefPubMedPubMedCentral
10.
Wejse C, Olesen R, Rabna P, Kaestel P, Gustafson P, Aaby P, Andersen PL, Glerup H, Sodemann M: Serum 25-hydroxyvitamin D in a West African population of tuberculosis patients and unmatched healthy controls. Am J Clin Nutr. 2007, 86: 1376-1383.PubMed
11.
Deeb KK, Trump DL, Johnson CS: Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer. 2007, 7: 684-700. 10.1038/nrc2196.CrossRefPubMed
12.
Nejentsev S, Godfrey L, Snook H, Rance H, Nutland S, Walker NM, Lam AC, Guja C, Ionescu-Tirgoviste C, Undlien DE, Ronningen KS, Tuomilehto-Wolf E, Tuomilehto J, Newport MJ, Clayton DG, Todd JA: Comparative high-resolution analysis of linkage disequilibrium and tag single nucleotide polymorphisms between populations in the vitamin D receptor gene. Hum Mol Genet. 2004, 13: 1633-1639. 10.1093/hmg/ddh169.CrossRefPubMed
13.
Zinser G, Packman K, Welsh J: Vitamin D(3) receptor ablation alters mammary gland morphogenesis. Development. 2002, 129: 3067-3076.PubMed
14.
Welsh J: Vitamin D and breast cancer: insights from animal models. Am J Clin Nutr. 2004, 80: 1721S-1724S.PubMed
15.
Welsh J: Vitamin D and prevention of breast cancer. Acta Pharmacol Sin. 2007, 28: 1373-1382. 10.1111/j.1745-7254.2007.00700.x.CrossRefPubMed
16.
International Agency for Research on Cancer: Vitamin D and cancer. IACR Working Group Reports. 2008, Lyon, France: International Agency for Research on Cancer, 5:
17.
Chlebowski RT, Johnson KC, Kooperberg C, Pettinger M, Wactawski-Wende J, Rohan T, Rossouw J, Lane D, O'Sullivan MJ, Yasmeen S, Hiatt RA, Shikany JM, Vitolins M, Khandekar J, Hubbell FA: Calcium plus vitamin D supplementation and the risk of breast cancer. J Natl Cancer Inst. 2008, 100: 1581-1591. 10.1093/jnci/djn360.CrossRefPubMedPubMedCentral
18.
Zinser GM, Suckow M, Welsh J: Vitamin D receptor (VDR) ablation alters carcinogen-induced tumorigenesis in mammary gland, epidermis and lymphoid tissues. J Steroid Biochem Mol Biol. 2005, 97: 153-164. 10.1016/j.jsbmb.2005.06.024.CrossRefPubMed
19.
Neuhouser ML, Sorensen B, Hollis BW, Ambs A, Ulrich CM, McTiernan A, Bernstein L, Wayne S, Gilliland F, Baumgartner K, Baumgartner R, Ballard-Barbash R: Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors. Am J Clin Nutr. 2008, 88: 133-139.PubMedPubMedCentral
20.
Abbas S, Chang-Claude J, Linseisen J: Plasma 25-hydroxyvitamin D and premenopausal breast cancer risk in a German case-control study. Int J Cancer. 2009, 124: 250-255. 10.1002/ijc.23904.CrossRefPubMed
21.
Abbas S, Linseisen J, Chang-Claude J: Dietary vitamin D and calcium intake and premenopausal breast cancer risk in a German case-control study. Nutr Cancer. 2007, 59: 54-61. 10.1080/01635580701390223.CrossRefPubMed
22.
Yao S, Sucheston LE, Millen AE, Johnson CS, Trump DL, Nesline MK, Davis W, Hong CC, McCann SE, Hwang H, Kulkarni S, Edge SB, O'Connor TL, Ambrosone CB: Pretreatment serum concentrations of 25-hydroxyvitamin D and breast cancer prognostic characteristics: a case-control and a case-series study. PLoS One. 2011, 6: e17251-10.1371/journal.pone.0017251.CrossRefPubMedPubMedCentral
23.
Ambrosone CB, Ciupak GL, Bandera EV, Jandorf L, Bovbjerg DH, Zirpoli G, Pawlish K, Godbold J, Furberg H, Fatone A, Valdimarsdottir H, Yao S, Li Y, Hwang H, Davis W, Roberts M, Sucheston L, Demissie K, Amend KL, Tartter P, Reilly J, Pace BW, Rohan T, Sparano J, Raptis G, Castaldi M, Estabrook A, Feldman S, Weltz C, Kemeny M: Conducting molecular epidemiological research in the age of HIPAA: a multi-institutional case-control study of breast cancer in African-American and European-American women. J Oncol. 2009, 2009: 871250-CrossRefPubMedPubMedCentral
24.
The International HapMap Consortium: The International HapMap Project. Nature. 2003, 426: 789-796. 10.1038/nature02168.CrossRef
25.
26.
Xu Z, Kaplan NL, Taylor JA: TAGster: efficient selection of LD tag SNPs in single or multiple populations. Bioinformatics. 2007, 23: 3254-3255. 10.1093/bioinformatics/btm426.CrossRefPubMedPubMedCentral
27.
Tsai HJ, Choudhry S, Naqvi M, Rodriguez-Cintron W, Burchard EG, Ziv E: Comparison of three methods to estimate genetic ancestry and control for stratification in genetic association studies among admixed populations. Hum Genet. 2005, 118: 424-433. 10.1007/s00439-005-0067-z.CrossRefPubMed
28.
Pritchard JK, Stephens M, Donnelly P: Inference of population structure using multilocus genotype data. Genetics. 2000, 155: 945-959.PubMedPubMedCentral
29.
Luna A, Nicodemus KK: snp.plotter: an R-based SNP/haplotype association and linkage disequilibrium plotting package. Bioinformatics. 2007, 23: 774-776. 10.1093/bioinformatics/btl657.CrossRefPubMed
30.
Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ, Altshuler D: The structure of haplotype blocks in the human genome. Science. 2002, 296: 2225-2229. 10.1126/science.1069424.CrossRefPubMed
31.
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC: PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007, 81: 559-575. 10.1086/519795.CrossRefPubMedPubMedCentral
32.
Zhang W, Duan S, Kistner EO, Bleibel WK, Huang RS, Clark TA, Chen TX, Schweitzer AC, Blume JE, Cox NJ, Dolan ME: Evaluation of genetic variation contributing to differences in gene expression between populations. Am J Hum Genet. 2008, 82: 631-640. 10.1016/j.ajhg.2007.12.015.CrossRefPubMedPubMedCentral
33.
Signorello LB, Williams SM, Zheng W, Smith JR, Long J, Cai Q, Hargreaves MK, Hollis BW, Blot WJ: Blood vitamin d levels in relation to genetic estimation of African ancestry. Cancer Epidemiol Biomarkers Prev. 2010, 19: 2325-2331. 10.1158/1055-9965.EPI-10-0482.CrossRefPubMedPubMedCentral
34.
Curran JE, Vaughan T, Lea RA, Weinstein SR, Morrison NA, Griffiths LR: Association of A vitamin D receptor polymorphism with sporadic breast cancer development. Int J Cancer. 1999, 83: 723-726. 10.1002/(SICI)1097-0215(19991210)83:6<723::AID-IJC4>3.0.CO;2-3.CrossRefPubMed
35.
Sillanpaa P, Hirvonen A, Kataja V, Eskelinen M, Kosma VM, Uusitupa M, Vainio H, Mitrunen K: Vitamin D receptor gene polymorphism as an important modifier of positive family history related breast cancer risk. Pharmacogenetics. 2004, 14: 239-245. 10.1097/00008571-200404000-00003.CrossRefPubMed
36.
Hou MF, Tien YC, Lin GT, Chen CJ, Liu CS, Lin SY, Huang TJ: Association of vitamin D receptor gene polymorphism with sporadic breast cancer in Taiwanese patients. Breast Cancer Res Treat. 2002, 74: 1-7. 10.1023/A:1016048900049.CrossRefPubMed
37.
Arai H, Miyamoto KI, Yoshida M, Yamamoto H, Taketani Y, Morita K, Kubota M, Yoshida S, Ikeda M, Watabe F, Kanemasa Y, Takeda E: The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene. J Bone Miner Res. 2001, 16: 1256-1264. 10.1359/jbmr.2001.16.7.1256.CrossRefPubMed
38.
Fang Y, van Meurs JB, Bergink AP, Hofman A, van Duijn CM, van Leeuwen JP, Pols HA, Uitterlinden AG: Cdx-2 polymorphism in the promoter region of the human vitamin D receptor gene determines susceptibility to fracture in the elderly. J Bone Miner Res. 2003, 18: 1632-1641. 10.1359/jbmr.2003.18.9.1632.CrossRefPubMed
39.
Abbas S, Nieters A, Linseisen J, Slanger T, Kropp S, Mutschelknauss EJ, Flesch-Janys D, Chang-Claude J: Vitamin D receptor gene polymorphisms and haplotypes and postmenopausal breast cancer risk. Breast Cancer Res. 2008, 10: R31-10.1186/bcr1994.CrossRefPubMedPubMedCentral
40.
John EM, Schwartz GG, Koo J, Wang W, Ingles SA: Sun exposure, vitamin D receptor gene polymorphisms, and breast cancer risk in a multiethnic population. Am J Epidemiol. 2007, 166: 1409-1419. 10.1093/aje/kwm259.CrossRefPubMed
41.
VandeVord PJ, Wooley PH, Darga LL, Severson RK, Wu B, Nelson DA: Genetic determinants of bone mass do not relate with breast cancer risk in US white and African-American women. Breast Cancer Res Treat. 2006, 100: 103-107. 10.1007/s10549-006-9228-6.CrossRefPubMed
42.
Trabert B, Malone KE, Daling JR, Doody DR, Bernstein L, Ursin G, Marchbanks PA, Strom BL, Humphrey MC, Ostrander EA: Vitamin D receptor polymorphisms and breast cancer risk in a large population-based case-control study of Caucasian and African-American women. Breast Cancer Res. 2007, 9: R84-10.1186/bcr1833.CrossRefPubMedPubMedCentral
43.
Poynter JN, Jacobs ET, Figueiredo JC, Lee WH, Conti DV, Campbell PT, Levine AJ, Limburg P, Le Marchand L, Cotterchio M, Newcomb PA, Potter JD, Jenkins MA, Hopper JL, Duggan DJ, Baron JA, Haile RW: Genetic variation in the vitamin D receptor (VDR) and the vitamin D-binding protein (GC) and risk for colorectal cancer: results from the Colon Cancer Family Registry. Cancer Epidemiol Biomarkers Prev. 2010, 19: 525-536. 10.1158/1055-9965.EPI-09-0662.CrossRefPubMedPubMedCentral
44.
Kahles H, Morahan G, Todd JA, Badenhoop K: Association analyses of the vitamin D receptor gene in 1654 families with type I diabetes. Genes Immun. 2009, 10 (Suppl 1): S60-63.CrossRefPubMedPubMedCentral
45.
Townsend K, Banwell CM, Guy M, Colston KW, Mansi JL, Stewart PM, Campbell MJ, Hewison M: Autocrine metabolism of vitamin D in normal and malignant breast tissue. Clin Cancer Res. 2005, 11: 3579-3586. 10.1158/1078-0432.CCR-04-2359.CrossRefPubMed
Metadata
Title
Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study
Authors
Song Yao
Gary Zirpoli
Dana H Bovbjerg
Lina Jandorf
Chi Chen Hong
Hua Zhao
Lara E Sucheston
Li Tang
Michelle Roberts
Gregory Ciupak
Warren Davis
Helena Hwang
Candace S Johnson
Donald L Trump
Susan E McCann
Foluso Ademuyiwa
Karen S Pawlish
Elisa V Bandera
Christine B Ambrosone
Publication date
01-04-2012
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 2/2012
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3162

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