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Serum 25-hydroxyvitamin D and breast cancer in the military: a case–control study utilizing pre-diagnostic serum

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Abstract

Purpose

The objective of this study was to ascertain whether a relationship exists between pre-diagnostic serum levels of 25-hydroxyvitamin D (25(OH)D) and risk of breast cancer in young women.

Methods

About 600 incident cases of breast cancer were matched to 600 controls as part of a nested case–control study that utilized pre-diagnostic sera. Logistic regression was used to assess the relationship between serum 25(OH)D concentration and breast cancer risk, controlling for race and age.

Results

According to the conditional logistic regression for all subjects, odds ratios for breast cancer by quintile of serum 25(OH)D from lowest to highest were 1.2, 1.0, 0.9, 1.1, and 1.0 (reference) (p trend = 0.72). After multivariate regression for subjects whose blood had been collected within 90 days preceding diagnosis, odds ratios for breast cancer by quintile of serum 25(OH)D from lowest to highest were 3.3, 1.9, 1.7, 2.6, and 1.0 (reference) (p trend = 0.09).

Conclusions

An inverse association between serum 25(OH)D concentration and risk of breast cancer was not present in the principal analysis, although an inverse association was present in a small subgroup analysis of subjects whose blood had been collected within 90 days preceding diagnosis. Further prospective studies of 25(OH)D and breast cancer risk are needed.

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References

  1. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62(1):10–29

    Article  PubMed  Google Scholar 

  2. Gorham E, Garland C, Garland F (1989) Acid haze air pollution and breast and colon cancer in 20 Canadian cities. Can J Publ Health 80:96–100

    CAS  Google Scholar 

  3. Gorham ED, Garland FC, Garland CF (1990) Sunlight and breast cancer incidence in the USSR. Int J Epidemiol 19(4):820–824

    Article  PubMed  CAS  Google Scholar 

  4. Grant WB (2002) An ecologic study of dietary and solar ultraviolet-B links to breast carcinoma mortality rates. Cancer 94(1):272–281

    Article  PubMed  Google Scholar 

  5. Garland C, Gorham E, Mohr S, Grant W, Giovannucci E, Lipkin M et al (2007) Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem Mol Biol 103(3–5):708–711

    Article  PubMed  CAS  Google Scholar 

  6. Mohr S, Garland C, Gorham E, Grant W, Garland F (2008) Relationship between low ultraviolet B irradiance and higher breast cancer risk in 107 countries. Breast J 14(3):255–260

    Article  PubMed  Google Scholar 

  7. Grant WB (2012) Relation between prediagnostic serum 25-hydroxyvitamin D level and incidence of breast, colorectal, and other cancers. J Photochem Photobiol B 101(2):130–136, 3 Nov

    Google Scholar 

  8. Gorham E, Garland F, Garland C (1990) Sunlight and breast cancer incidence in the USSR. Int J Epidemiol 19(4):820–824

    Article  PubMed  CAS  Google Scholar 

  9. Garland C, al. e. (1990) Levels of serum 25-hydroxyvitamin D, 60 individuals aged 60+ years [Graph]. Rancho Bernardo, CA

  10. Garland C, Garland F, Gorham E (1992) Could sunscreens increase melanoma risk? Am J Public Health 82:614–615

    Article  PubMed  CAS  Google Scholar 

  11. Freedman D, Dosemeci M, McGlynn K (2002) Sunlight and mortality from breast, ovarian, colon, prostate, and non-melanoma skin cancer: a composite death certificate based case-control study. Occup Environ Med 59(4):257–262

    Article  PubMed  CAS  Google Scholar 

  12. Looker AC, Dawson-Hughes B, Calvo MS, Gunter EW, Sahyoun NR (2002) Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III. Bone 30(5):771–777

    Article  PubMed  CAS  Google Scholar 

  13. Garland F, Garland C, Gorham E, Young J Jr (1990) Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prev Med 19:614–622

    Article  PubMed  CAS  Google Scholar 

  14. John E, Schwartz G, Dreon D, Koo J (1999) Vitamin D and breast cancer risk: the NHANES I epidemiologic follow-up study, 1971–1975 to 1992. Cancer Epidemiol Biomark Prev 8:399–406

    CAS  Google Scholar 

  15. Shin MH, Holmes MD, Hankinson SE, Wu K, Colditz GA, Willett WC (2002) Intake of dairy products, calcium, and vitamin D and risk of breast cancer. J Natl Cancer Inst 94(17):1301–1311

    Article  PubMed  CAS  Google Scholar 

  16. Rossi M, McLaughlin JK, Lagiou P, Bosetti C, Talamini R, Lipworth L et al (2009) Vitamin D intake and breast cancer risk: a case-control study in Italy. Ann Oncol 20(2):374–378

    Article  PubMed  CAS  Google Scholar 

  17. Robien K, Cutler GJ, Lazovich D (2007) Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women’s Health Study. Cancer Causes Control 18(7):775–782

    Article  PubMed  Google Scholar 

  18. Abbas S, Linseisen J, Chang-Claude J (2007) Dietary vitamin D and calcium intake and premenopausal breast cancer risk in a German case-control study. Nutr Cancer 59(1):54–61

    Article  PubMed  CAS  Google Scholar 

  19. Abbas S, Chang-Claude J, Linseisen J (2009) Plasma 25-hydroxyvitamin D and premenopausal breast cancer risk in a German case-control study. Int J Cancer 124(1):250–255

    Article  PubMed  CAS  Google Scholar 

  20. Abbas S, Linseisen J, Slanger T, Kropp S, Mutschelknauss EJ, Flesch-Janys D et al (2008) Serum 25-hydroxyvitamin D and risk of post-menopausal breast cancer—results of a large case-control study. Carcinogenesis 29(1):93–99

    Article  PubMed  CAS  Google Scholar 

  21. Bertone-Johnson ER, Chen WY, Holick MF, Hollis BW, Colditz GA, Willett WC et al (2005) Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 14(8):1991–1997

    Article  PubMed  CAS  Google Scholar 

  22. Chlebowski R, Johnson K, Kooperberg C et al (2008) Calcium plus vitamin D supplementation and the risk of breast cancer. JNCI 100:1581–1591

    Article  PubMed  CAS  Google Scholar 

  23. Crew KD, Gammon MD, Steck SE, Hershman DL, Cremers S, Dworakowski E et al (2009) Association between plasma 25-hydroxyvitamin D and breast cancer risk. Cancer Prev Res (Phila) 2(6):598–604

    Article  CAS  Google Scholar 

  24. Engel P, Fagherazzi G, Boutten A, Dupre T, Mesrine S, Boutron-Ruault MC et al (2010) Serum 25(OH) vitamin D and risk of breast cancer: a nested case-control study from the French E3N cohort. Cancer Epidemiol Biomarkers Prev 19(9):2341–2350

    Article  PubMed  CAS  Google Scholar 

  25. Green AK, Hankinson SE, Bertone-Johnson ER, Tamimi RM (2010) Mammographic density, plasma vitamin D levels and risk of breast cancer in postmenopausal women. Int J Cancer 127(3):667–674

    Article  PubMed  CAS  Google Scholar 

  26. Lowe LC, Guy M, Mansi JL, Peckitt C, Bliss J, Wilson RG et al (2005) Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population. Eur J Cancer 41(8):1164–1169

    Article  PubMed  CAS  Google Scholar 

  27. Rejnmark L, Tietze A, Vestergaard P, Buhl L, Lehbrink M, Heickendorff L et al (2009) Reduced prediagnostic 25-hydroxyvitamin D levels in women with breast cancer: a nested case-control study. Cancer Epidemiol Biomarkers Prev 18(10):2655–2660

    Article  PubMed  CAS  Google Scholar 

  28. Garland C, Comstock G, Garland F, Helsing K, Shaw E, Gorham E (1989) Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Lancet 2:1176–1178

    Article  PubMed  CAS  Google Scholar 

  29. Tworoger SS, Lee IM, Buring JE, Rosner B, Hollis BW, Hankinson SE (2007) Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of incident ovarian cancer. Cancer Epidemiol Biomarkers Prev 16(4):783–788

    Article  PubMed  CAS  Google Scholar 

  30. Garland C, Gorham E, Garland F (2009) Vitamin D for cancer prevention: global perspective. Ann Epidemiol 19(7):468–483

    Google Scholar 

  31. Freedman DM, Chang SC, Falk RT, Purdue MP, Huang WY, McCarty CA et al (2008) Serum levels of vitamin D metabolites and breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev 17(4):889–894

    Article  PubMed  CAS  Google Scholar 

  32. McCullough ML, Stevens VL, Patel R, Jacobs EJ, Bain EB, Horst RL et al (2009) Serum 25-hydroxyvitamin D concentrations and postmenopausal breast cancer risk: a nested case control study in the Cancer Prevention Study-II Nutrition Cohort. Breast Cancer Res 11(4):R64

    Article  PubMed  Google Scholar 

  33. Almquist M, Bondeson AG, Bondeson L, Malm J, Manjer J (2010) Serum levels of vitamin D, PTH and calcium and breast cancer risk-a prospective nested case-control study. Int J Cancer Journal international du cancer 127(9):2159–2168, 1 Nov

    Google Scholar 

  34. Eliassen AH, Spiegelman D, Hollis BW, Horst RL, Willett WC, Hankinson SE (2011) Plasma 25-hydroxyvitamin D and risk of breast cancer in the Nurses’ Health Study II. Breast Cancer Res BCR 13(3):R50

    Google Scholar 

  35. Mohr SB, Gorham ED, Alcaraz JE, Kane CJ, Macera CA, Parsons JK, et al (2011) Serum 25-hydroxyvitamin D and prevention of breast cancer: pooled analysis. Anticancer Res 31(9):2939–2948, Sep

    Google Scholar 

  36. Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H (2012) Meta-analysis: serum vitamin D and breast cancer risk. Eur J Cancer 46(12):2196–2205, Aug

    Google Scholar 

  37. Gandini S, Boniol M, Haukka J, Byrnes G, Cox B, Sneyd MJ, et al (2012) Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer 128(6):1414–1424, 15 Mar

    Google Scholar 

  38. Chen P, Hu P, Xie D, Qin Y, Wang F, Wang H (2010) Meta-analysis of vitamin D, calcium and the prevention of breast cancer. Breast Cancer Res Treatment 121(2):469–477, Jun

    Google Scholar 

  39. Rubertone MV, Brundage JF (2002) The Defense Medical Surveillance System and the Department of Defense serum repository: glimpses of the future of public health surveillance. Am J Public Health 92(12):1900–1904

    Article  PubMed  Google Scholar 

  40. Ersfeld DL, Rao DS, Body JJ, Sackrison JL Jr, Miller AB, Parikh N et al (2004) Analytical and clinical validation of the 25 OH vitamin D assay for the LIAISON automated analyzer. Clin Biochem 37(10):867–874

    Article  PubMed  CAS  Google Scholar 

  41. Wagner D, Hanwell HE, Vieth R (2009) An evaluation of automated methods for measurement of serum 25-hydroxyvitamin D. Clin Biochem 42(15):1549–1556

    Article  PubMed  CAS  Google Scholar 

  42. Carter GD, Carter R, Jones J, Berry J (2004) How accurate are assays for 25-hydroxyvitamin D? Data from the international vitamin D external quality assessment scheme. Clin Chem 50(11):2195–2197

    Article  PubMed  CAS  Google Scholar 

  43. Mantel N (1963) Chi square tests with one degree of freedom; extensions of the Mantel-Haenszel procedure. J Am Stat Assoc 58:690–700

    Google Scholar 

  44. Bluff JE, Brown NJ, Reed MW, Staton CA (2008) Tissue factor, angiogenesis and tumour progression. Breast Cancer Res BCR 10(2):204

    Google Scholar 

  45. Grant WB (2011) Effect of interval between serum draw and follow-up period on relative risk of cancer incidence with respect to 25-hydroxyvitamin D level: Implications for meta-analyses and setting vitamin D guidelines. Dermato-Endocrinology 3(3):199–204

    PubMed  CAS  Google Scholar 

  46. Merck Manual of Diagnosis and Therapy (2003) Breast disorders: cancer. In: Robert S, Porter M (ed). Merck Publishing Group, Whitehouse Station

  47. van den Brandt PA, Spiegelman D, Yaun SS, Adami HO, Beeson L, Folsom AR, et al (2000) Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol 152(6):514–527, 15 Sep

    Google Scholar 

  48. Pandey S, Maheshwari A, Bhattacharya S (2010) The impact of female obesity on the outcome of fertility treatment. J Hum Reprod Sci 3(2):62–67

    Article  PubMed  Google Scholar 

  49. Gesink Law DC, Maclehose RF, Longnecker MP (2007) Obesity and time to pregnancy. Hum Reprod 22(2):414–420, Feb

    Google Scholar 

  50. Nolte R, Franckowiak SC, Crespo CJ, Andersen RE (2002) U.S. military weight standards: what percentage of U.S. young adults meet the current standards? Am J Med 113(6):486–490

    Article  PubMed  Google Scholar 

  51. Welsh J (2004) Vitamin D and breast cancer: insights from animal models. Am J Clin Nutr 80(6 Suppl):1721S–1724S

    PubMed  CAS  Google Scholar 

  52. Eisman J, Martin T, MacIntyre I, Mosely J (1979) 1,25-dihydroxyvitamin D3 receptor in breast cancer cells. Lancet 2:1335–1336

    Article  PubMed  CAS  Google Scholar 

  53. Pendas-Franco N, Gonzalez-Sancho JM, Suarez Y, Aguilera O, Steinmeyer A, Gamallo C et al (2007) Vitamin D regulates the phenotype of human breast cancer cells. Differentiation 75(3):193–207

    Article  PubMed  CAS  Google Scholar 

  54. Wang Q, Lee D, Sysounthone V, Chandraratna RAS, Christakos S, Korah R et al (2001) 1,25-dihydroxyvitamin D3 and retinoic acid analogues induce differentiation in breast cancer cells with function- and cell-specific additive effects. Breast Cancer Res Treat 67(2):157–168

    Article  PubMed  CAS  Google Scholar 

  55. Janowsky EC, Lester GE, Weinberg CR, Millikan RC, Schildkraut JM, Garrett PA et al (1999) Association between low levels of 1,25-dihydroxyvitamin D and breast cancer risk. Public Health Nutr 2(3):283–291

    Article  PubMed  CAS  Google Scholar 

  56. Hiatt RA, Krieger N, Lobaugh B, Drezner MK, Vogelman JH, Orentreich N (1998) Prediagnostic serum vitamin D and breast cancer. J Natl Cancer Inst 90(6):461–463

    Article  PubMed  CAS  Google Scholar 

  57. Friedenreich CM (2012) Physical activity and breast cancer: review of the epidemiologic evidence and biologic mechanisms. Recent Results Cancer Res 188:125–139

    Google Scholar 

  58. Anderson LN, Cotterchio M, Kirsh VA, Knight JA (2011) Ultraviolet sunlight exposure during adolescence and adulthood and breast cancer risk: a population-based case-control study among Ontario women. Am J Epidemiol 174(3):293–304, 9 Jun

    Google Scholar 

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Acknowledgments

This research was supported by a Congressional allocation to the Penn State Cancer Institute of the Hershey Medical Center, Hershey, PA, through the Department of the Navy, Bureau of Medicine and Surgery, under Work Unit No. 60126 at the Naval Health Research Center (San Diego, CA, USA). The views presented here are solely the opinions of the authors and do not represent an official position of the Department of the Navy, the Department of Defense, or the U.S. Government. Approved for public release; distribution unlimited. Thanks to Dr. Angelee Ferber of the U.S. Army Medical Research and Development Command for providing the blood samples used in this study and for her outstanding support of the research. Thanks to June J. Kim, B.S., of Naval Health Research Center for her valued work editing the manuscript.

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Correspondence to Sharif B. Mohr.

Appendix

Appendix

See Figs. 3, 4 and 5

Fig. 3
figure 3

Serum 25(OH)D level and risk of breast cancer, 536 nonwhite women, unmatched, and unadjusted for covariates

Fig. 4
figure 4

Odds ratio for breast cancer, by serum 25(OH)D concentration, 108 nonwhite women, blood drawn <90 days before diagnosis, unmatched, and unadjusted for covariates

Fig. 5
figure 5

Serum 25(OH)D level and risk of breast cancer, 248 women, blood drawn <90 days before diagnosis, unmatched, and unadjusted for covariates

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Mohr, S.B., Gorham, E.D., Alcaraz, J.E. et al. Serum 25-hydroxyvitamin D and breast cancer in the military: a case–control study utilizing pre-diagnostic serum. Cancer Causes Control 24, 495–504 (2013). https://doi.org/10.1007/s10552-012-0140-6

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  • DOI: https://doi.org/10.1007/s10552-012-0140-6

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