Meta-analysis not find low vitamin D years before breast cancer – Aug 2010

Meta-analysis: Serum vitamin D and breast cancer risk

European Journal of Cancer, Volume 46, Issue 12 , Pages 2196-2205, August 2010
* Lu Yin
* , Norma Grandi
* , Elke Raum
* , Ulrike Haug
* , Volker Arndt
* , Hermann Brenner
o Corresponding Author InformationCorresponding author: Fax: +49 6221 548142.
Received 24 February 2010; received in revised form 17 March 2010; accepted 30 March 2010. published online 26 April 2010.

We reviewed and summarised observational epidemiological studies regarding the association between serum vitamin D (measured as 25(OH)D levels) and the risk of breast cancer (BC). Relevant studies published until September 2009 were identified by systematically electronic searching Ovid Medline, EMBASE and ISI Web of Knowledge databases and by cross-referencing. The following data were extracted in a standardised manner from eligible studies: first author, publication year, country, study design, characteristics of the study population, duration of follow-up, BC incidence/BC mortality according to serum 25-hydroxyvitamin D OH)D) and the respective ratios, and covariates adjusted for in the analysis. All existing observational epidemiological studies that reported at least one serum 25(OH)D level in subjects in any time period before or after a diagnosis of breast cancer were included in our review. Individual and summary risk ratios (RRs) for an increase of serum 25(OH)D by 20ng/ml were calculated using meta-analysis methods. Only 25(OH)D was considered. Overall, 10 articles were included. Specific results for BC incidence were reported in nine articles and for BC mortality in one article. In meta-analyses, summary RRs (95% confidence interval (CI for an increase of 25(OH)D by 20ng/ml were 0.59 (0.48–0.73), 0.92 (0.82–1.04) and 0.73 (0.60–0.88) with P values of <0.001, 0.164 and 0.001 for case-control studies, nested case-control studies and both study designs combined, respectively. No indication for publication bias was found, but there was large heterogeneity between studies.

In conclusion, while case-control studies with measurement of 25(OH)D after diagnosis suggest an inverse association, a statistically significant inverse association remained unconfirmed in prospective studies with measurement of 25(OH)D years before diagnosis. Further studies are needed to clarify the potential role and the relevant exposure time regarding vitamin D and breast cancer risk.

References ( only 5 from 2009)

  1. Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer?. Int J Epidemiol. 1980;9:227–231
  2. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004;79:362–371
  3. Giovannucci E. The epidemiology of vitamin D and cancer incidence and mortality: a review (United States). Cancer Causes Control. 2005;16:83–95
  4. Garland CF, Grant WB, Mohr SB, Gorham ED, Garland FC. What is the dose–response relationship between vitamin D and cancer risk?. Nutr Rev. 2007;65:S91–S95
  5. IARC. Vitamin D and cancer. IARC working group reports, vol. 5. Lyon: International Agency or Research on Cancer; 25 November 2008.
  6. Garland FC, Garland CF, Gorham ED, Young JF. Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prev Med. 1990;19:614–622
  7. Gorham ED, Garland FC, Garland CF. Sunlight and breast cancer incidence in the USSR. Int J Epidemiol. 1990;19:820–824
  8. Grant WB. An ecologic study of dietary and solar ultraviolet-B links to breast carcinoma mortality rates. Cancer. 2002;94:272–281
  9. Boscoe FP, Schymura MJ. Solar ultraviolet-B exposure and cancer incidence and mortality in the United States, 1993–2002. BMC Cancer. 2006;6:264
  10. van der Wielen RP, Lowik MR, van den Berg H, et al. Serum vitamin D concentrations among elderly people in Europe. Lancet. 1995;346:207–210
  11. Lips P, Duong T, Oleksik A, et al. A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial. J Clin Endocrinol Metab. 2001;86(3):1212–1221
  12. Simard A, Vobecky J, Vobecky JS. Vitamin D deficiency and cancer of the breast: an unprovocative ecological hypothesis. Can J Public Health. 1991;82:300–303
  13. Potischman N, Swanson CA, Coates RJ, et al. Intake of food groups and associated micronutrients in relation to risk of early-stage breast cancer. Int J Cancer. 1999;82:315–321
  14. Levi F, Pasche C, Lucchini F, La Vecchia C. Dietary intake of selected micronutrients and breast-cancer risk. Int J Cancer. 2001;91:260–263
  15. Shin MH, Holmes MD, Hankinson SE, et al. Intake of dairy products, calcium, and vitamin d and risk of breast cancer. J Natl Cancer Inst. 2002;94:1301–1311
  16. McCullough ML, Rodriguez C, Diver WR, et al. Dairy, calcium, and vitamin D intake and postmenopausal breast cancer risk in the cancer prevention study II nutrition cohort. Cancer Epidemiol Biomarkers Prev. 2005;14:2898–2904
  17. 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
  18. Lin J, Manson JE, Lee IM, et al. Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med. 2007;167:1050–1059
  19. Robien K, Cutler GJ, Lazovich D. Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women’s Health Study. Cancer Causes Control. 2007;18:775–782
  20. Kuper H, Yang L, Sandin S, et al. Prospective study of solar exposure, dietary vitamin D intake, and risk of breast cancer among middle-aged women. Cancer Epidemiol Biomarkers Prev. 2009;18:2558–2561
  21. Holick MF. The use and interpretation of assays for vitamin D and its metabolites. J Nutr. 1990;120:1464–1469
  22. Garland CF, Gorham ED, Mohr SB, et al. Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem Mol Biol. 2007;103:708–711
  23. Greenland S, Longnecker MP. Methods for trend estimation from summarized dose–response data, with applications to meta-analysis. Am J Epidemiol. 1992;135:1301–1309
  24. Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions 4.2.6 updated September 2006. In: The Cochrane library issue 4. Chichester, UK: John Wiley and Sons Ltd.; 2006.
  25. Normand SL. Meta-analysis: formulating, evaluating, combining, and reporting. Stat Med. 1999;18:321–359
  26. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–188
  27. Lipsey M, Wilson D. Practical meta-analysis. Thousand Oaks, CA: Sage; 2001;
  28. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA. 2000;283:2008–2012
  29. Rothstein HR, Sutton AJ, Borenstein M. Publication bias in meta-analysis: prevention, assessment and adjustments. Chichester, England: Wiley; 2005;
  30. Colston KW, Lowe LC, Mansi JL, Campbell MJ. Vitamin D status and breast cancer risk. Anticancer Res. 2006;26:2573–2580
  31. Lowe LC, Guy M, Mansi JL, et al. 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
  32. Freedman DM, Looker AC, Chang SC, Graubard BI. Prospective study of serum vitamin D and cancer mortality in the United States. J Natl Cancer Inst. 2007;99:1594–1602
  33. Bertone-Johnson ER, Chen WY, Holick MF, et al. Plasma 25-hydroxyvitamin D and 1, 25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2005;14:1991–1997
  34. Chlebowski RT, Johnson KC, Kooperberg C, et al. Calcium plus vitamin D supplementation and the risk of breast cancer. J Natl Cancer Inst. 2008;100:1581–1591
  35. Freedman DM, Chang SC, Falk RT, et al. Serum levels of vitamin D metabolites and breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev. 2008;17:889–894
  36. McCullough ML, Stevens VL, Patel R, et al. 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. 2009;11:R64
  37. Abbas S, Linseisen J, Slanger T, et al. Serum 25-hydroxyvitamin D and risk of post-menopausal breast cancer – results of a large case-control study. Carcinogenesis. 2008;29:93–99
  38. 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
  39. Crew KD, Gammon MD, Steck SE, et al. Association between plasma 25-hydroxyvitamin D and breast cancer risk. Cancer Prev Res (Phila Pa). 2009;2:598–604
  40. Rejnmark L, Tietze A, Vestergaard P, et al. Reduced prediagnostic 25-hydroxyvitamin D levels in women with breast cancer: a nested case-control study. Cancer Epidemiol Biomarkers Prev. 2009;18:2655–2660
  41. Scragg R, Holdaway I, Singh V, et al. Serum 25-hydroxyvitamin D3 is related to physical activity and ethnicity but not obesity in a multicultural workforce. Aust N Z J Med. 1995;25:218–223
  42. Looker AC. Do body fat and exercise modulate vitamin D status?. Nutr Rev. 2007;65:S124–S126
  43. Brock KE, Graubard BI, Fraser DR, et al. Predictors of vitamin D biochemical status in a large sample of middle-aged male smokers in Finland. Eur J Clin Nutr. 2010;64:280–288
Will have to look at the PDF to understand this. It may be correct, but have seen a great many papers which have had major errors before. One example: restricted the study participants to those who took < 450 IU vitamin D per day, and tried to compare the cancer rates of those few who had > 20 ng of vitamin D with those who were below 20 ng. They totally ignored the literature which indicates that the anti-cancer benefit does not start until > 40 ng

See also:

The most recent items in category Cancer - Breast



5099 visitors, last modified 10 Sep, 2010,
Printer Friendly Follow this page for updates