Skip to main content
NCBI home page
Meta Gene logoLink to Meta Gene
. 2013 Dec 21;2:41–49. doi: 10.1016/j.mgene.2013.09.008

Current evidence on the four polymorphisms of VDR and breast cancer risk in Caucasian women☆

Baohong Yang a,1, Shuzhen Liu a,1, Xueling Yang b, Yue Wang c, Xianzhi Zhao d, Dejie Zheng a, Jianfeng Gao a, Kaili Chen e, Yanfang Gao a, Liang Liu a, Haipeng Ren a, Wenhui Wang a, Yuanling Qi a, Guohua Yu a,⁎
PMCID: PMC4287799  PMID: 25606388

Abstract

There have been a few epidemiological studies reporting VDR polymorphisms including Fok1, Bsm1, Apa1 and Taq1with breast cancer incidence and therefore risk. The results however are controversial, often due to smaller sample size. Concerning most of the studies were performed on Caucasian women, we conducted this comprehensive meta-analysis encompassing 38,151 cases and 47,546 controls (Fok1: 13,152 cases, 17,443 controls; Bsm1: 14,755 cases, 18,633 controls; Apa1: 3080 cases, 3412 controls; Taq1: 7164 cases, 8068 controls) to better understand roles of the polymorphisms in breast cancer development among Caucasian population. We did not find any association of the most controversial genotype Fok1 with breast cancer risk in Caucasian women (ff vs. FF: OR = 1.05, 95% CI = 0.95–1.22, P = 0.32 for heterogeneity; ff vs. Ff: OR = 1.05, 95% CI = 0.94–1.17, P = 0.40; ff vs. Ff + FF: OR = 1.07, 95% CI = 0.95–1.14, P = 0.37 and ff + Ff vs. FF: OR = 1.04, 95% CI = 0.99–1.09, P = 0.23). For Bsm1, Apa1 and Taq1, no significant association was also not found in the homozygote comparison, heterozygote comparison, recessive and dominant models respectively. In conclusion, the current analysis suggested that the four polymorphisms (Fok1, Bsm1, Apa1 and Taq1) of VDR may be not associated with breast cancer risk in Caucasian women.

Keywords: VDR, Polymorphism, Breast cancer risk, Meta-analysis

Highlights

  • •

    We added some new studies.

  • •

    The polymorphisms of VDR gene do not contribute to breast cancer susceptibility.

  • •

    This analysis is conducted in Caucasian women.

Introduction

Vitamin D was originally discovered by Edward Mellanby in 1919 (Mellanby, 1919, Mellanby, 2009). Over the past years, studies indicated that vitamin D not only has an important function in bones, but it also significantly affects cell proliferation and differentiation. In cancer cells, the active metabolite of vitamin D, 1,25-dihydroxycholecalciferol (1,25(OH)2D3) can suppress cell proliferation (Thorne and Campbell, 2008). Many studies suggested that serum concentrations of vitamin D metabolites have been inversely associated with risk for breast cancer development (Bertone-Johnson et al., 2005, Shin et al., 2002).

The effects of vitamin D for the most part are correlated with nuclear vitamin D receptor (VDR). It has been well established that the active hormone 1,25(OH)2D3 can induce a cascade of gene regulation and signaling molecules by binding to VDR (Welsh, 2011). However a series of polymorphisms in VDR gene have been reported. They include Bsm1, Apa1, Taq1 restriction sites, variable PolyA length and Fok1 restriction site (Köstner et al., 2009). Of these polymorphic sites Bsm1 and Apa1 are substitutions on intron 8 whereas Taq1 brings about substitution of cytosine to thymine on exon 9. The Fork1 restriction enzyme identifies a polymorphic site in exon 2 at the 50 end of the VDR gene.

Over the years, most of the molecular epidemiological studies were performed on Caucasian women to assess the associations of different VDR polymorphisms with breast cancer risk (Abbas et al., 2008, Anderson et al., 2011, Buyru et al., 2003, Chen et al., 2005b, Curran et al., 1999, Dalessandri et al., 2011, Dunning et al., 1999, Engel et al., 2012, Gapska et al., 2009, Guy et al., 2004, Hefler et al., 2004, Ingles et al., 2000, Lowe et al., 2005, Lundin et al., 1999, McCullough et al., 2007, McKay et al., 2009, Rollison et al., 2011, Ruggiero et al., 1998, Sillanpaa et al., 2004, Sinotte et al., 2008, Trabert et al., 2007). However, the results are inconsistent, which might be caused by the limitation of individual studies. Therefore we performed this meta-analysis which combines data from all published literatures to get a more precise evaluation of the association in Caucasian women.

Methods

Search strategy

In this meta-analysis, a comprehensive literature research of the US National Library of Medicine's PubMed database, ISI Web of Knowledge, Medline, Embase and Google Scholar Search (update to December, 2012) was conducted using the search terms including “breast cancer”, “vitamin D receptor (VDR)”, “polymorphism”, “Fok1”, “Apa1”, “Bsm1”, “Taq1”, and the combined phrases in order to obtain all genetic studies on the relationship of the polymorphisms with breast cancer in Caucasian women. We also used a hand search of references of original studies or reviewed articles on this topic to identify additional studies.

Data extraction

Data extraction was carried out independently by two investigators. For each eligible study, the following information was recorded: the first author's name, the year of publication, country of origin, genotyping methods, racial descent of the study population, number of cases and controls with different genotypes.

Statistical analysis

The strength of relationship between the four polymorphisms of VDR and breast cancer was assessed by using Crude OR with 95% CI. We examined the association using homozygote comparison, heterozygote comparison, dominant genetic model and recessive genetic model of the four polymorphisms. Between-study heterogeneity was evaluated by the χ2-based Q-test and the heterogeneity was considered significant when P < 0.05 (Lau et al., 1997). Fixed-effects model (the Mantel–Haenszel method) was used to pool the data when the P-value of Q-test ≥ 0.05, otherwise, random-effects model (the DerSimonian and Laird method) was selected (DerSimonian and Laird, 1986, Mantel and Haenszel, 1959). These two models provided similar results when between-study heterogeneity was absent. Both funnel plot and Egger's test were used to assess the publication bias (P < 0.05 was considered representative of statistical significance) (Egger et al., 1997). All statistical analyses were performed using STATA11.0 software.

Results

Eligible studies

The main characteristics of all the 21 studies are shown in Table 1. Genotype distribution of the studied polymorphisms among cancer cases and controls of the studies is shown in the supplementary material. The genotyping method contains the classic polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay, DNA sequencing, Affymetrix, TaqMan, MassARRAY system and Allele-specific PCR. All studies were case–control and Caucasian descent. Hospital based controls were carried out in ten studies, while population based controls were carried out in 11 studies. The distribution of genotypes in the controls was all in agreement with Hardy–Weinberg equilibrium except for five studies (Buyru et al., 2003, Hefler et al., 2004, Ruggiero et al., 1998, Sinotte et al., 2008, Trabert et al., 2007).

Table 1.

The main characteristics of all the studies in this meta-analysis.

Author Year Country Ethnicity Source of control Matching criteria Case/control Genotyping methods Studied polymorphism HWE
Curran 1999 Australia Caucasian Population Age 135/110 PCR–RFLP Fok1, Apa1, Taq1 Y
Dunning1 1999 UK Caucasian Hospital Age, residential area 211/268 PCR–RFLP Taq1 Y
Dunning2 1999 UK Caucasian Hospital Age, residential area 740/359 PCR–RFLP Taq1 Y
Lundin 1999 Sweden Caucasian Population Age 111/130 PCR–RFLP Taq1 Y
Ingles 2000 America Caucasian Hospital Residential area 143/300 PCR–RFLP Bsm1 Y
Guy 2004 UK Caucasian Hospital Age 398/427 PCR–RFLP Fok1, Bsm1 Y
Sillanpaa 2004 Finnish Caucasian Hospital Age, residential area 483/482 PCR–RFLP Apa1, Taq1 Y
Hefler 2004 Germany Caucasian Population Age 1699/1963 Microarray system Bsm1 N
Chen 2005 Turkey Caucasian Hospital Age and residential area 1234/1676 TaqMan Fok1 Y
Lowe 2005 UK Caucasian Hospital Age, residential area 179/179 PCR–RFLP Bsm1 Y
McKay 2008 America Caucasian Population Age, hormone status 4657/6578 TaqMan Fok1, Bsm1 Y
Dana E. Rollison 2011 America Caucasian Population Age, regional area 2318/2512 PCR Bsm1, Fokl Y
Ruggiero 1998 Italy European Population Age, residential area 88/167 PCR–RFLP Bsm1 N
Engel 2012 America Caucasian Population Race, regional area 806/1650 MassARRAY system Apa1, Fokl, Taq1 Y
McCullough 2007 America Caucasian Hospital Age, residential area 500/500 TaqMan Fok1, Apa1, Bsm1, Taq1 Y
Trabert 2007 America Caucasian Hospital Age, residential area 1136/965 PCR–RFLP Bsm1 Y
Abbas 2008 Germany Caucasian Population Age 1408/2612 PCR–RFLP Fok1, Taq1 Y
Buyru 2003 Turkey Caucasian Population NA 27/78 PCR–RFLP Bsm1, Taq1 N
Sinotte1 2008 Canada Caucasian Population Regional match 225/463 Allele–specific PCR Fok, Bsm1 Y
Scott 2008 Poland Caucasian Hospital Age, regional match 960/800 RT-PCR Apa1, Fokl Y
Anderson 2011 Canada Caucasian Population Age 6201/6509 MassARRAY system Apa1, Fokl, Bsm1, Taq1 Y
Dalessandri, 2011 America Caucasian Population Age, ethnicity 164/174 Allele-specific PCT Apa1 Y
Sinotte2 2008 Canada Caucasian Population Regional match 622/974 Allele-specific PCR Fok1, Bsm1 Y
Open in a new tab

Meta-analysis

The main results of this meta-analysis and the heterogeneity tests were shown in Table 2. Overall, we did not find any association of all the studied polymorphisms with breast cancer risk in Caucasian women.

Table 2.

The main results of this meta-analysis.

Polymorphisms ORs and 95% CI Pa ORs and 95% CI Pa ORs and 95% CI Pa ORs and 95% CI P
ForkI ff vs. FF
1.05(0.95–1.22)		 0.32 ff vs. Ff
1.05(0.94–1.17)		 0.40 ff vs. Ff + FF
1.07(0.95–1.14)		 0.37 ff + Ff vs. FF
1.04(0.99–1.09)		 0.23



ApaI aa vs. AA
1.00(0.87–1.18)		 0.34 aa vs. Aa
0.87(0.85–1.10)		 0.11 aa vs. Aa + AA
0.88(0.86–1.12)		 0.25 Aa + aa vs. AA
1.08(0.80–1.30)b 		0.01



BsmI bb vs. BB
1.00(0.90–1.11)b 		0.01 bb vs. Bb
1.02(0.9–1.22)		 0.06 bb + Bb vs. BB
1.01(0.95–1.03)b 		0.04 bb vs. BB + Bb
1.01(0.91–1.13)b 		0.02



TaqI tt vs. TT
1.05(0.95–1.16)		 0.12 tt vs. Tt
1.00(0.91–1.10)		 0.21 tt vs. TT + Tt
1.02(0.93–1.12)		 0.06 tt + Tt vs. TT
1.04(0.97–1.11)		 0.41
Open in a new tab

Abbreviations: CI, confidence interval; OR, odds ratio.

a

P-value of Q-test for heterogeneity test.

b

Random model was used.

For Fok1, no association with breast cancer risk was found in all the models (ff vs. FF: OR = 1.05, 95% CI = 0.95–1.22, P = 0.32 for heterogeneity; ff vs. Ff: OR = 1.05, 95% CI = 0.94–1.17, P = 0.40; ff vs. Ff + FF: OR = 1.07, 95% CI = 0.95–1.14, P = 0.37 and ff + Ff vs. FF: OR = 1.04, 95% CI = 0.99–1.09, P = 0.23).

For Bsm1, Apa1 and Taq1, we also did not find any significant association in the homozygote comparison, heterozygote comparison, recessive and dominant models respectively.

Publication bias

Both Begg's funnel plot and Egger's test were performed to assess the publication bias of the literature. The shape of the funnel plots did not reveal any evidence of obvious asymmetry in the overall meta-analysis (Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5). Then, Egger's test was used to provide statistical evidence of funnel plot symmetry. The results still did not present any obvious evidence of publication bias (data not shown).

Fig. 1.

Fig. 1

Open in a new tab

Flow diagram of study identification.

Fig. 2.

Fig. 2

Open in a new tab

OR on breast cancer not associated with Bsm1 for the bb genotype compared with the BB genotype.

Fig. 3.

Fig. 3

Open in a new tab

OR on breast cancer not associated with Taq1 for the tt genotype compared with the TT genotype.

Fig. 4.

Fig. 4

Open in a new tab

Funnel plot analysis to detect publication bias. Each point represents a separate study for the indicated association (ff vs. FF).

Fig. 5.

Fig. 5

Open in a new tab

Funnel plot analysis to detect publication bias. Each point represents a separate study for the indicated association (aa vs. AA).

Discussion

This meta-analysis encompassing 21 studies involving 38,151 cases and 47,546 controls was conducted to investigate the potential association between four polymorphisms of VDR and breast cancer risk in Caucasian women. Overall, we did not find any association of all the studied four SNPs with breast cancer risk in Caucasian women.

Up to now, Fok1 is the most controversial SNP concerning its relationship with breast cancer risk, VDR FF allele in combination with long-Poly A was reported to be a risk factor in the UK (Guy et al., 2004), whereas in another report Chen (Chen et al., 2005a) found VDR ff to be a risk factor in the Nurses' Health study in the USA. In 2009, the meta-analysis conducted by Tang et al. indicated a positive association between VDR ff and augmented risk for breast cancer in European women (Tang et al., 2009). Yet other reports did not find any correlation between Fok1 polymorphism and breast cancer incidence. Most recently, Shahbazi et al. found no statistically significant association between Fok1 genotypes and breast cancer risk in Iranian breast cancer patients (Shahbazi et al., 2013). Our analysis involving 13,152 cases and 17,443 controls confirmed that Fok1 was not overall significantly associated with breast cancer risk in Caucasian women.

Compared to Fok1, the Bsm1 exhibits strong linkage disequilibrium with Apa1 and Taq1, located at the 30 untranslated region (30 UTR) of the VDR gene. This haplotype may affect mRNA stability and processing as well as regulation of VDR transcription and translation (Gapska et al., 2009, Trabert et al., 2007). Among all the studies, only four studies which were performed on Caucasian women reported an increased risk of breast cancer with the Bsm1 bb genotype (Buyru et al., 2003, Lundin et al., 1999, Ogunkolade et al., 2002, Whitfield et al., 2001). Curran et al. claimed that allele frequencies of the Apa1 polymorphism showed a significant association with breast cancer risk, other studies found no association (Curran et al., 1999). Comparing t allele carriers with non-carriers, Abbas et al. conducted one study suggesting that the Taq1 polymorphism was associated with a significantly increased breast cancer risk in estrogen receptor positive patients (Abbas et al., 2008). Other studies did not find significant overall association in Caucasian women. Concerning the strong linkage disequilibrium of the three polymorphisms, combinations of the three variants may be more discriminating as risk factors than a single one.

As in all research, our study has limitations. Firstly, the controls were not uniformly defined. Secondly, since there is a lack of detailed individual information on genotypes of Bsm1, Apa1 and Taq1, we could not perform the pooled analysis of linkage disequilibrium and the combined genotypes of these three SNPs. Thirdly, due to the original data of the eligible studies are unavailable. We did not perform the analysis adjusted for some covariates such as: age, dietary vitamin D, sun exposure, intake and steroid hormone receptor status.

In conclusion, this analysis suggested that the four polymorphisms (Fok1, Bsm1, Apa1 and Taq1) of VDR may be not associated with breast cancer risk in Caucasian women.

Footnotes

☆

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

References

  1. Abbas S., Nieters A., Linseisen J., Slanger T., Kropp S., Mutsch- elknauss E.J., Flesch-Janys D., Chang-Claude J. Vitamin D receptor gene polymorphisms and haplotypes and postmenopausal breast cancer risk. Breast Cancer Res. 2008;10:R31. doi: 10.1186/bcr1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson L.N., Cotterchio M., Cole D.E., Knight J.A. Vitamin D-related genetic variants, interactions with vitamin D exposure, and breast cancer risk among Caucasian women in Ontario. Cancer Epidemiol. Biomarkers Prev. 2011;20(8):1708–1717. doi: 10.1158/1055-9965.EPI-11-0300. (2011 Aug) [DOI] [PubMed] [Google Scholar]
  3. Bertone-Johnson E.R., Chen W.Y., Holick M.F., Hollis B.W., Colditz G.A., Willett W.C., Hankinson S.E. Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol. Biomarkers Prev. 2005;14:1991–1997. doi: 10.1158/1055-9965.EPI-04-0722. [DOI] [PubMed] [Google Scholar]
  4. Buyru N., Tezol A., Yosunkaya-Fenerci E., Dalay N. Vitamin D receptor gene polymorphisms in breast cancer. Exp. Mol. Med. 2003;35:550–555. doi: 10.1038/emm.2003.72. [DOI] [PubMed] [Google Scholar]
  5. Chen W.Y., Berone-Johnson E.R., Hunter D.J., Willett W.C., Hankinson S.E. Association between polymorphism in the vitamin D receptor and breast cancer risk. Cancer Epidemiol. Biomarkers Prev. 2005;14:2335–2339. doi: 10.1158/1055-9965.EPI-05-0283. [DOI] [PubMed] [Google Scholar]
  6. Chen W.Y., Bertone-Johnson E.R., Hunter D.J., Willett W.C., Hankinson S.E. Associations between polymorphisms in the vitamin D receptor and breast cancer risk. Cancer Epidemiol. Biomarkers Prev. 2005;14:2335–2339. doi: 10.1158/1055-9965.EPI-05-0283. [DOI] [PubMed] [Google Scholar]
  7. Curran J.E., Vaughan T., Lea R.A., Weinstein S.R., Morrison N.A., Griffiths L.R. Association of A vitamin D receptor poly morphism with sporadic breast cancer development. Int. J. Cancer. 1999;83:723–726. doi: 10.1002/(sici)1097-0215(19991210)83:6<723::aid-ijc4>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  8. Dalessandri K.M., Miike R., Wiencke J.K., Farren G., Pugh T.W., Manjeshwar S., DeFreese D.C., Jupe E.R. Vitamin D receptor polymorphisms and breast cancer risk in a high-incidence population: a pilot study. J. Am. Coll. Surg. 2011;215(5):652–657. doi: 10.1016/j.jamcollsurg.2012.06.413. (2012 Nov) [DOI] [PubMed] [Google Scholar]
  9. DerSimonian R., Laird N. Meta-analysis in clinical trials. Control. Clin. Trials. 1986;7:177–188. doi: 10.1016/0197-2456(86)90046-2. [DOI] [PubMed] [Google Scholar]
  10. Dunning A.M., McBride S., Gregory J., Durocher F., Foster N.A., Healey C.S., Smith N., Pharoah P.D., Luben R.N., Easton D.F., Ponder B.A. No association between androgen or vitamin D receptor gene polymorphisms and risk of breast cancer. Carcinogenesis. 1999;20:2131–2135. doi: 10.1093/carcin/20.11.2131. [DOI] [PubMed] [Google Scholar]
  11. Egger M., Davey Smith G., Schneider M., Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–634. doi: 10.1136/bmj.315.7109.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Engel L.S., Orlow I., Sima C.S., Satagopan J., Mujumdar U., Roy P., Yoo S., Sandler D.P., Alavanja M.C. Vitamin D receptor gene haplotypes and polymorphisms and risk of breast cancer: a nested case–control study. Cancer Epidemiol. Biomarkers Prev. 2012;21(10):1856–1867. doi: 10.1158/1055-9965.EPI-12-0551. (Oct) [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gapska P., Scott R.J., Serrano-Fernandez P., Huzarski T., Byrski T., Kładny J., Gronwald J., Górski B., Cybulski C., Lubinski J., Debniak T. Vitamin D receptor variants and breast cancer risk in the Polish population. Breast Cancer Res. Treat. 2009;115(3):629–633. doi: 10.1007/s10549-008-0107-1. (Epub 2008 Jun 29) [DOI] [PubMed] [Google Scholar]
  14. Guy M., Lowe L.C., Bretherton-Watt D., Mansi J.L., Peckitt C., Bliss J., Wilson R.G., Thomas V., Colston K.W. Vitamin D receptor gene polymorphisms and breast cancer risk. Clin. Cancer Res. 2004;10:5472–5481. doi: 10.1158/1078-0432.CCR-04-0206. [DOI] [PubMed] [Google Scholar]
  15. Hefler L.A., Tempfer C.B., Grimm C., Lebrecht A., Ulbrich E., Heinze G., Leodolter S., Schneeberger C., Mueller M.W., Muendlein A., Koelbl H. Estrogen-metabolizing gene polymorphisms in the assessment of breast carcinoma risk and fibroadenoma risk in Caucasian women. Cancer. 2004;101:264–269. doi: 10.1002/cncr.20361. [DOI] [PubMed] [Google Scholar]
  16. Ingles S.A., Garcia D.G., Wang W., Nieters A., Henderson B.E., Kolonel L.N., Haile R.W., Coetzee G.A. Vitamin D receptor genotype and breast cancer in Latinas (United States) Cancer Causes Control. 2000;11:25–30. doi: 10.1023/a:1008979417618. [DOI] [PubMed] [Google Scholar]
  17. Köstner K., Denzer N., Müller C.S., 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;29:3511–3536. [PubMed] [Google Scholar]
  18. Lau J., Ioannidis J.P., Schmid C.H. Quantitative synthesis in systematic reviews. Ann. Intern. Med. 1997;127:820–826. doi: 10.7326/0003-4819-127-9-199711010-00008. [DOI] [PubMed] [Google Scholar]
  19. Lowe L.C., Guy M., Mansi J.L., Peckitt C., Bliss J., Wilson R.G., Colston K.W. Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population. Eur. J. Cancer. 2005;41:1164–1169. doi: 10.1016/j.ejca.2005.01.017. [DOI] [PubMed] [Google Scholar]
  20. Lundin A.C., Soderkvist P., Eriksson B., Bergman-Jungestrom M., Wingren S. Association of breast cancer progression with a vitamin D receptor gene polymorphism. South–East Sweden Breast Cancer Group. Cancer Res. 1999;59:2332–2334. [PubMed] [Google Scholar]
  21. Mantel N., Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J. Natl. Cancer Inst. 1959;22:719–748. [PubMed] [Google Scholar]
  22. McCullough M.L., Stevens V.L., Diver W.R., Feigelson H.S., Rodriguez C., Bostick R.M., Thun M.J., Calle E.E. Vitamin D pathway gene polymorphisms, diet, and risk of postmenopausal breast cancer: a nested case–control study. Breast Cancer Res. 2007;9:R9. doi: 10.1186/bcr1642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. McKay J.D., McCullough M.L., Ziegler R.G., Kraft P., Saltzman B.S., Riboli E., Barricarte A., Berg C.D., Bergland G., Bingham S., Brustad M., Bueno-de-Mesquita H.B., Burdette L., Buring J., Calle E.E., Chanock S.J., Clavel-Chapelon F., Cox D.G., Dossus L., Feigelson H.S., Haiman C.A., Hankinson S.E., Hoover R.N., Hunter D.J., Husing A., Kaaks R., Kolonel L.N., Le Marchand L., Linseisen J., McCarty C.A., Overvad K., Panico S., Purdue M.P., Stram D.O., Stevens V.L., Trichopoulos D., Willett W.C., Yuenger J., Thun M.J. Vitamin D receptor polymorphisms and breast cancer risk: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium. Cancer Epidemiol. Biomarkers Prev. 2009;18(1):297–305. doi: 10.1158/1055-9965.EPI-08-0539. (Jan) [DOI] [PubMed] [Google Scholar]
  24. Mellanby E. An experimental investigation on rickets. Lancet. 1919;1:407–412. doi: 10.1111/j.1753-4887.1976.tb05815.x. [DOI] [PubMed] [Google Scholar]
  25. Mellanby E. An experimental investigation on rickets. Nutr. Rev. 2009;34:338–340. doi: 10.1111/j.1753-4887.1976.tb05815.x. [DOI] [PubMed] [Google Scholar]
  26. Ogunkolade B.W., Boucher B.J., Prahl J.M., Bustin S.A., Burrin J.M., Noonan K., North B.V., Mannan N., McDermott M.F., DeLuca H.F., Hitman G.A. Vitamin D receptor (VDR) mRNA and VDR protein levels in relation to vitamin D status, insulin secretory capacity, and VDR genotype in Bangladeshi Asians. Diabetes. 2002;51:2294–2300. doi: 10.2337/diabetes.51.7.2294. [DOI] [PubMed] [Google Scholar]
  27. Rollison D.E., Cole A.L., Tung K.H., Slattery M.L., Baumgartner K.B., Byers T., Wolff R.K., Giuliano A.R. Vitamin D intake, vitamin D receptor polymorphisms, and breast cancer risk among women living in the southwestern U.S. Breast Cancer Res. Treat. 2011;132(2):683–691. doi: 10.1007/s10549-011-1885-4. (2012 Apr) [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ruggiero M., Pacini S., Aterini S., Fallai C., Ruggiero C., Pacini P. Vitamin D receptor gene polymorphism is associated with metastatic breast cancer. Oncol. Res. 1998;10:43–46. [PubMed] [Google Scholar]
  29. Shahbazi S., Alavi S., Majidzadeh-A K., Ghaffarpour M., Soleimani A., Mahdian R. BsmI but not FokI polymorphism of VDR gene is contributed in breast cancer. Med. Oncol. 2013;30:393. doi: 10.1007/s12032-012-0393-7. [DOI] [PubMed] [Google Scholar]
  30. Shin M.H., Holmes M.D., Hankinson S.E., Wu K., Colditz G.A., Willett W.C. Intake of dairy products, calcium, and vitamin D and risk of breast cancer. J. Natl. Cancer Inst. 2002;94:1301–1311. doi: 10.1093/jnci/94.17.1301. [DOI] [PubMed] [Google Scholar]
  31. Sillanpaa P., Hirvonen A., Kataja V., Eskelinen M., Kosma V.M., 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. doi: 10.1097/00008571-200404000-00003. [DOI] [PubMed] [Google Scholar]
  32. Sinotte M., Rousseau F., Ayotte P., Dewailly E., Diorio C., Giguere Y., Berube S., Brisson J. Vitamin D receptor polymorphisms (FokI, BsmI) and breast cancer risk: association replication in two case–control studies within French Canadian population. Endocr. Relat. Cancer. 2008;15(4):975–983. doi: 10.1677/ERC-08-0056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Tang C., Chen N., Wu M., Yuan H., Du Y. FokI polymorphism of vitamin D receptor gene contributes to breast cancer susceptibility: a meta-analysis. Breast Cancer Res. Treat. 2009;117:391–399. doi: 10.1007/s10549-008-0262-4. [DOI] [PubMed] [Google Scholar]
  34. Thorne J., Campbell M.J. The vitamin D receptor in cancer. Proc. Nutr. Soc. 2008;67:15–27. doi: 10.1017/S0029665108006964. [DOI] [PubMed] [Google Scholar]
  35. Trabert B., Malone K.E., Daling J.R., Doody D.R., Bernstein L., Ursin G., Marchbanks P.A., Strom B.L., Humphrey M.C., Ostrander E.A. 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. doi: 10.1186/bcr1833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Welsh J. Vitamin D metabolism in mammary gland and breast cancer. Mol. Cell. Endocrinol. 2011;347:55–60. doi: 10.1016/j.mce.2011.05.020. [DOI] [PubMed] [Google Scholar]
  37. Whitfield G.K., Remus L.S., Jurutka P.W., Zitzer H., Oza A.K., Dang H.T., Haussler C.A., Galligan M.A., Thatcher M.L., Encinas Dominguez C., Haussler M.R. Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Mol. Cell. Endocrinol. 2001;177:145–159. doi: 10.1016/s0303-7207(01)00406-3. [DOI] [PubMed] [Google Scholar]

Articles from Meta Gene are provided here courtesy of Elsevier

RESOURCES