Circulating levels of 25-hydroxyvitamin D and risk of breast cancer: a nested case-control study

IntroductionExperimental evidence suggests a protective role for circulating 25-hydroxyvitamin D (25(OH)D) in breast cancer development, but the results of epidemiological studies have been inconsistent.MethodsWe conducted a case-control study nested within two prospective cohorts, the New York University Women's Health Study and the Northern Sweden Mammary Screening Cohort. Blood samples were collected at enrollment, and women were followed up for breast cancer ascertainment. In total, 1,585 incident breast cancer cases were individually-matched to 2,940 controls. Of these subjects, 678 cases and 1,208 controls contributed two repeat blood samples, at least one year apart. Circulating levels of 25(OH)D were measured, and multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression.ResultsNo association was observed between circulating levels of 25(OH)D and overall breast cancer risk (multivariate-adjusted model OR = 0.94, 95% CI = 0.76-1.16 for the highest vs. lowest quintile, ptrend = 0.30). The temporal reliability of 25(OH)D measured in repeat blood samples was high (intraclass correlation coefficients for season-adjusted 25(OH)D > 0.70). An inverse association between 25(OH)D levels and breast cancer risk was observed among women who were ≤ 45 years of age (ORQ5-Q1 = 0.48, 95% CI = 0.30-0.79, ptrend = 0.01) or premenopausal at enrollment (ORQ5-Q1 = 0.67, 95% CI = 0.48-0.92, ptrend = 0.03).ConclusionsCirculating 25(OH)D levels were not associated with breast cancer risk overall, although we could not exclude the possibility of a protective effect in younger women. Recommendations regarding vitamin D supplementation should be based on considerations other than breast cancer prevention.

[1]  Kelly Smith,et al.  Vitamin D-3 receptor as a target for breast cancer prevention. , 2003, The Journal of nutrition.

[2]  M. Holick,et al.  P12 Analysis of 25-hydroxyvitamin d3-1a-hydroxylase in normal and malignant breast tissue , 2005 .

[3]  R. Chlebowski Vitamin D and breast cancer: interpreting current evidence , 2011, Breast Cancer Research.

[4]  A. Ciampi,et al.  Reliability and validity of commercially available, direct radioimmunoassays for measurement of blood androgens and estrogens in postmenopausal women. , 2001, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[5]  J. Chang-Claude,et al.  Plasma 25‐hydroxyvitamin D and premenopausal breast cancer risk in a German case‐control study , 2009, International journal of cancer.

[6]  L. Brinton,et al.  Prospective case-control study of premenopausal serum estradiol and testosterone levels and breast cancer risk , 2010, Breast Cancer Research.

[7]  Annamaria Colao,et al.  Vitamin D and Cancer , 2012, Front. Endocrin..

[8]  J. Welsh Vitamin D and breast cancer: insights from animal models. , 2004, The American journal of clinical nutrition.

[9]  J. A. Calvin,et al.  Levels of maternal serum alpha-fetoprotein (AFP) in pregnant women and subsequent breast cancer risk. , 1998, American journal of epidemiology.

[10]  J. Malm,et al.  Serum levels of vitamin D, PTH and calcium and breast cancer risk—a prospective nested case–control study , 2010, International journal of cancer.

[11]  M. Schymura,et al.  Comparison of active and cancer registry-based follow-up for breast cancer in a prospective cohort study. , 1999, American journal of epidemiology.

[12]  F. Clavel-Chapelon,et al.  Serum 25(OH) Vitamin D and Risk of Breast Cancer: A Nested Case-Control Study from the French E3N Cohort , 2010, Cancer Epidemiology, Biomarkers & Prevention.

[13]  Christine L. Taylor,et al.  Dietary Reference Intakes for Calcium and Vitamin D , 2016, Pediatric Clinical Practice Guidelines & Policies.

[14]  T. Trikalinos,et al.  Vitamin D With or Without Calcium Supplementation for Prevention of Cancer and Fractures: An Updated Meta-analysis for the U.S. Preventive Services Task Force , 2011, Annals of Internal Medicine.

[15]  C. Davis Vitamin D and cancer: current dilemmas and future research needs. , 2008, The American journal of clinical nutrition.

[16]  W. Willett,et al.  Plasma 25-hydroxyvitamin D and risk of breast cancer in the Nurses' Health Study II , 2011, Breast Cancer Research.

[17]  C. Weinberg,et al.  Association between low levels of 1,25-dihydroxyvitamin D and breast cancer risk , 1999, Public Health Nutrition.

[18]  S. van Buuren Multiple imputation of discrete and continuous data by fully conditional specification , 2007, Statistical methods in medical research.

[19]  A. Neugut,et al.  Association between Plasma 25-Hydroxyvitamin D and Breast Cancer Risk , 2009, Cancer Prevention Research.

[20]  M. Lehtinen,et al.  Serum 25-hydroxyvitamin D at pregnancy and risk of breast cancer in a prospective study. , 2010, European journal of cancer.

[21]  P. Strax,et al.  Endogenous hormones and breast cancer: A prospective cohort study , 1991, Breast Cancer Research and Treatment.

[22]  J. Manson,et al.  The influence of health and lifestyle characteristics on the relation of serum 25-hydroxyvitamin D with risk of colorectal and breast cancer in postmenopausal women. , 2012, American journal of epidemiology.

[23]  J. Welsh,et al.  Impact of the Vitamin D3 receptor on growth-regulatory pathways in mammary gland and breast cancer , 2002, The Journal of Steroid Biochemistry and Molecular Biology.

[24]  R. Shore,et al.  Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study , 2004, British Journal of Cancer.

[25]  E. Somers International Agency for Research on Cancer. , 1985, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[26]  M. Thun,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 , 2009, Breast Cancer Research.

[27]  C. McCarty,et al.  Low vitamin D status is associated with physical inactivity, obesity and low vitamin D intake in a large US sample of healthy middle-aged men and women , 2010, The Journal of Steroid Biochemistry and Molecular Biology.

[28]  Paul S Albert,et al.  Using lowess to remove systematic trends over time in predictor variables prior to logistic regression with quantile categories , 2003, Statistics in medicine.

[29]  R. Hiatt,et al.  Calcium plus vitamin D supplementation and the risk of breast cancer. , 2008, Journal of the National Cancer Institute.

[30]  J. Chang-Claude,et al.  Serum 25-hydroxyvitamin D and risk of postmenopausal breast cancer-results of a large case-control study , 2007 .

[31]  C. McCarty,et al.  Serum Levels of Vitamin D Metabolites and Breast Cancer Risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial , 2008, Cancer Epidemiology Biomarkers & Prevention.

[32]  A. LaCroix,et al.  Predictors of serum 25-hydroxyvitamin D concentrations among postmenopausal women: the Women's Health Initiative Calcium plus Vitamin D clinical trial. , 2010, The American journal of clinical nutrition.

[33]  Peizhan Chen,et al.  Meta-analysis of vitamin D, calcium and the prevention of breast cancer , 2010, Breast Cancer Research and Treatment.

[34]  A. Prentice,et al.  Vitamin D across the lifecycle: physiology and biomarkers. , 2008, The American journal of clinical nutrition.

[35]  I. Romieu,et al.  Serum 25-hydroxyvitamin D and risk of breast cancer: results of a large population-based case–control study in Mexican women , 2012, Cancer Causes & Control.

[36]  W. Willett,et al.  Plasma 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D and Risk of Breast Cancer , 2005, Cancer Epidemiology Biomarkers & Prevention.

[37]  D. Whiteman,et al.  Physical activity and cancer prevention: a systematic review of clinical trials , 2011, Cancer Causes & Control.

[38]  L. Weinehall,et al.  Cardiovascular disease and diabetes in the Northern Sweden Health and Disease Study Cohort- evaluation of risk factors and their interactions , 2003, Scandinavian journal of public health. Supplement.

[39]  R. Jorde,et al.  Tracking of serum 25-hydroxyvitamin D levels during 14 years in a population-based study and during 12 months in an intervention study. , 2010, American journal of epidemiology.

[40]  A. Tietze,et al.  Reduced Prediagnostic 25-Hydroxyvitamin D Levels in Women with Breast Cancer: A Nested Case-Control Study , 2009, Cancer Epidemiology, Biomarkers & Prevention.

[41]  E. Giovannucci,et al.  Calcium, vitamin D and colorectal cancer chemoprevention. , 2011, Best practice & research. Clinical gastroenterology.

[42]  L. Mosekilde,et al.  [Vitamin D and breast cancer]. , 2007, Ugeskrift for laeger.

[43]  R. Hayes,et al.  Circulating 25-Hydroxyvitamin D and the Risk of Rarer Cancers: Design and Methods of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers , 2010, American journal of epidemiology.

[44]  J. Dungan Human Chorionic Gonadotropin and Alpha-Fetoprotein Concentrations in Pregnancy and Maternal Risk of Breast Cancer: A Nested Case-Control Study , 2009 .

[45]  J. Chang-Claude,et al.  Serum 25-hydroxyvitamin D and risk of post-menopausal breast cancer--results of a large case-control study. , 2007, Carcinogenesis.

[46]  M. Guy,et al.  Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population. , 2005, European journal of cancer.

[47]  M. Holick,et al.  Analysis of 25-hydroxyvitamin D3-1alpha-hydroxylase in normal and malignant breast tissue. , 2005, Anticancer research.

[48]  H. Hanwell,et al.  An evaluation of automated methods for measurement of serum 25-hydroxyvitamin D. , 2009, Clinical biochemistry.

[49]  R. Hayes,et al.  American Journal of Epidemiology Original Contribution Circulating 25-hydroxyvitamin D and Risk of Kidney Cancer Cohort Consortium Vitamin D Pooling Project of Rarer Cancers , 2022 .

[50]  C. Mathieu,et al.  Vitamin D and cancer , 2013, Cell cycle.