Circulating vitamin D and breast cancer risk: an international pooling project of 17 cohorts

Kala Visvanathan; Alison M. Mondul; Anne Zeleniuch-Jacquotte; Molin Wang; Mitchell H. Gail; Shiaw Shyuan Yaun; Stephanie J. Weinstein; Marjorie L. McCullough; A. Heather Eliassen; Nancy R. Cook; Claudia Agnoli; Martin Almquist; Amanda Black; Julie E. Buring; Chu Chen; Yu Chen; Tess Clendenen; Laure Dossus; Veronika Fedirko; Gretchen L. Gierach; Edward L. Giovannucci; Gary E. Goodman; Marc T. Goodman; Pascal Guénel; Göran Hallmans; Susan E. Hankinson; Ronald L. Horst; Tao Hou; Wen Yi Huang; Michael E. Jones; Corrine E. Joshu; Rudolf Kaaks; Vittorio Krogh; Tilman Kühn; Marina Kvaskoff; I. Min Lee; Yahya Mahamat-Saleh; Johan Malm; Jonas Manjer; Gertraud Maskarinec; Amy E. Millen; Toqir K. Mukhtar; Marian L. Neuhouser; Trude E. Robsahm; Minouk J. Schoemaker; Sabina Sieri; Malin Sund; Anthony J. Swerdlow; Cynthia A. Thomson; Giske Ursin; Jean Wactawski-Wende; Ying Wang; Lynne R. Wilkens; Yujie Wu; Emilie Zoltick; Walter C. Willett; Stephanie A. Smith-Warner; Regina G. Ziegler

doi:10.1007/s10654-022-00921-1

Circulating vitamin D and breast cancer risk: an international pooling project of 17 cohorts

Kala Visvanathan, Alison M. Mondul, Anne Zeleniuch-Jacquotte, Molin Wang, Mitchell H. Gail, Shiaw Shyuan Yaun, Stephanie J. Weinstein, Marjorie L. McCullough, A. Heather Eliassen, Nancy R. Cook, Claudia Agnoli, Martin Almquist, Amanda Black, Julie E. Buring, Chu Chen, Yu Chen, Tess Clendenen, Laure Dossus, Veronika Fedirko, Gretchen L. GierachEdward L. Giovannucci, Gary E. Goodman, Marc T. Goodman, Pascal Guénel, Göran Hallmans, Susan E. Hankinson, Ronald L. Horst, Tao Hou, Wen Yi Huang, Michael E. Jones, Corrine E. Joshu, Rudolf Kaaks, Vittorio Krogh, Tilman Kühn, Marina Kvaskoff, I. Min Lee, Yahya Mahamat-Saleh, Johan Malm, Jonas Manjer, Gertraud Maskarinec, Amy E. Millen, Toqir K. Mukhtar, Marian L. Neuhouser, Trude E. Robsahm, Minouk J. Schoemaker, Sabina Sieri, Malin Sund, Anthony J. Swerdlow, Cynthia A. Thomson, Giske Ursin, Jean Wactawski-Wende, Ying Wang, Lynne R. Wilkens, Yujie Wu, Emilie Zoltick, Walter C. Willett, Stephanie A. Smith-Warner, Regina G. Ziegler

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Abstract

Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42–68) years at blood collection and 63 (49–75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, calibrated to this assay to permit using a common metric. Study-specific relative risks (RRs) for season-standardized 25(OH)D concentrations were estimated by conditional logistic regression and combined by random-effects models. Circulating 25(OH)D increased from a median of 22.6 nmol/L in consortium-wide decile 1 to 93.2 nmol/L in decile 10. Breast cancer risk in each decile was not statistically significantly different from risk in decile 5 in models adjusted for breast cancer risk factors, and no trend was apparent (P-trend = 0.64). Compared to women with sufficient 25(OH)D based on Institute of Medicine guidelines (50– < 62.5 nmol/L), RRs were not statistically significantly different at either low concentrations (< 20 nmol/L, 3% of controls) or high concentrations (100– < 125 nmol/L, 3% of controls; ≥ 125 nmol/L, 0.7% of controls). RR per 25 nmol/L increase in 25(OH)D was 0.99 [95% confidence intervaI (CI) 0.95–1.03]. Associations remained null across subgroups, including those defined by body mass index, physical activity, latitude, and season of blood collection. Although none of the associations by tumor characteristics reached statistical significance, suggestive inverse associations were seen for distant and triple negative tumors. Circulating 25(OH)D, comparably measured in 17 international cohorts and season-standardized, was not related to subsequent incidence of invasive breast cancer over a broad range in vitamin D status.

Original language	English (US)
Pages (from-to)	11-29
Number of pages	19
Journal	European Journal of Epidemiology
Volume	38
Issue number	1
DOIs	https://doi.org/10.1007/s10654-022-00921-1
State	Published - Jan 2023

Keywords

25-Hydroxyvitamin D
Biomarker
Breast cancer
Calibration
Pooled analysis
Prospective cohort study
Vitamin D

ASJC Scopus subject areas

Epidemiology

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10.1007/s10654-022-00921-1

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Visvanathan, K., Mondul, A. M., Zeleniuch-Jacquotte, A., Wang, M., Gail, M. H., Yaun, S. S., Weinstein, S. J., McCullough, M. L., Eliassen, A. H., Cook, N. R., Agnoli, C., Almquist, M., Black, A., Buring, J. E., Chen, C., Chen, Y., Clendenen, T., Dossus, L., Fedirko, V., ... Ziegler, R. G. (2023). Circulating vitamin D and breast cancer risk: an international pooling project of 17 cohorts. European Journal of Epidemiology, 38(1), 11-29. https://doi.org/10.1007/s10654-022-00921-1

Visvanathan, K, Mondul, AM, Zeleniuch-Jacquotte, A, Wang, M, Gail, MH, Yaun, SS, Weinstein, SJ, McCullough, ML, Eliassen, AH, Cook, NR, Agnoli, C, Almquist, M, Black, A, Buring, JE, Chen, C, Chen, Y, Clendenen, T, Dossus, L, Fedirko, V, Gierach, GL, Giovannucci, EL, Goodman, GE, Goodman, MT, Guénel, P, Hallmans, G, Hankinson, SE, Horst, RL, Hou, T, Huang, WY, Jones, ME, Joshu, CE, Kaaks, R, Krogh, V, Kühn, T, Kvaskoff, M, Lee, IM, Mahamat-Saleh, Y, Malm, J, Manjer, J, Maskarinec, G, Millen, AE, Mukhtar, TK, Neuhouser, ML, Robsahm, TE, Schoemaker, MJ, Sieri, S, Sund, M, Swerdlow, AJ, Thomson, CA, Ursin, G, Wactawski-Wende, J, Wang, Y, Wilkens, LR, Wu, Y, Zoltick, E, Willett, WC, Smith-Warner, SA & Ziegler, RG 2023, 'Circulating vitamin D and breast cancer risk: an international pooling project of 17 cohorts', European Journal of Epidemiology, vol. 38, no. 1, pp. 11-29. https://doi.org/10.1007/s10654-022-00921-1

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title = "Circulating vitamin D and breast cancer risk: an international pooling project of 17 cohorts",

abstract = "Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42–68) years at blood collection and 63 (49–75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, calibrated to this assay to permit using a common metric. Study-specific relative risks (RRs) for season-standardized 25(OH)D concentrations were estimated by conditional logistic regression and combined by random-effects models. Circulating 25(OH)D increased from a median of 22.6 nmol/L in consortium-wide decile 1 to 93.2 nmol/L in decile 10. Breast cancer risk in each decile was not statistically significantly different from risk in decile 5 in models adjusted for breast cancer risk factors, and no trend was apparent (P-trend = 0.64). Compared to women with sufficient 25(OH)D based on Institute of Medicine guidelines (50– < 62.5 nmol/L), RRs were not statistically significantly different at either low concentrations (< 20 nmol/L, 3% of controls) or high concentrations (100– < 125 nmol/L, 3% of controls; ≥ 125 nmol/L, 0.7% of controls). RR per 25 nmol/L increase in 25(OH)D was 0.99 [95% confidence intervaI (CI) 0.95–1.03]. Associations remained null across subgroups, including those defined by body mass index, physical activity, latitude, and season of blood collection. Although none of the associations by tumor characteristics reached statistical significance, suggestive inverse associations were seen for distant and triple negative tumors. Circulating 25(OH)D, comparably measured in 17 international cohorts and season-standardized, was not related to subsequent incidence of invasive breast cancer over a broad range in vitamin D status.",

keywords = "25-Hydroxyvitamin D, Biomarker, Breast cancer, Calibration, Pooled analysis, Prospective cohort study, Vitamin D",

author = "Kala Visvanathan and Mondul, {Alison M.} and Anne Zeleniuch-Jacquotte and Molin Wang and Gail, {Mitchell H.} and Yaun, {Shiaw Shyuan} and Weinstein, {Stephanie J.} and McCullough, {Marjorie L.} and Eliassen, {A. Heather} and Cook, {Nancy R.} and Claudia Agnoli and Martin Almquist and Amanda Black and Buring, {Julie E.} and Chu Chen and Yu Chen and Tess Clendenen and Laure Dossus and Veronika Fedirko and Gierach, {Gretchen L.} and Giovannucci, {Edward L.} and Goodman, {Gary E.} and Goodman, {Marc T.} and Pascal Gu{\'e}nel and G{\"o}ran Hallmans and Hankinson, {Susan E.} and Horst, {Ronald L.} and Tao Hou and Huang, {Wen Yi} and Jones, {Michael E.} and Joshu, {Corrine E.} and Rudolf Kaaks and Vittorio Krogh and Tilman K{\"u}hn and Marina Kvaskoff and Lee, {I. Min} and Yahya Mahamat-Saleh and Johan Malm and Jonas Manjer and Gertraud Maskarinec and Millen, {Amy E.} and Mukhtar, {Toqir K.} and Neuhouser, {Marian L.} and Robsahm, {Trude E.} and Schoemaker, {Minouk J.} and Sabina Sieri and Malin Sund and Swerdlow, {Anthony J.} and Thomson, {Cynthia A.} and Giske Ursin and Jean Wactawski-Wende and Ying Wang and Wilkens, {Lynne R.} and Yujie Wu and Emilie Zoltick and Willett, {Walter C.} and Smith-Warner, {Stephanie A.} and Ziegler, {Regina G.}",

note = "Publisher Copyright: {\textcopyright} 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.",

year = "2023",

month = jan,

doi = "10.1007/s10654-022-00921-1",

language = "English (US)",

volume = "38",

pages = "11--29",

journal = "European Journal of Epidemiology",

issn = "0393-2990",

publisher = "Springer Netherlands",

number = "1",

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TY - JOUR

T1 - Circulating vitamin D and breast cancer risk

T2 - an international pooling project of 17 cohorts

AU - Visvanathan, Kala

AU - Mondul, Alison M.

AU - Zeleniuch-Jacquotte, Anne

AU - Wang, Molin

AU - Gail, Mitchell H.

AU - Yaun, Shiaw Shyuan

AU - Weinstein, Stephanie J.

AU - McCullough, Marjorie L.

AU - Eliassen, A. Heather

AU - Cook, Nancy R.

AU - Agnoli, Claudia

AU - Almquist, Martin

AU - Black, Amanda

AU - Buring, Julie E.

AU - Chen, Chu

AU - Chen, Yu

AU - Clendenen, Tess

AU - Dossus, Laure

AU - Fedirko, Veronika

AU - Gierach, Gretchen L.

AU - Giovannucci, Edward L.

AU - Goodman, Gary E.

AU - Goodman, Marc T.

AU - Guénel, Pascal

AU - Hallmans, Göran

AU - Hankinson, Susan E.

AU - Horst, Ronald L.

AU - Hou, Tao

AU - Huang, Wen Yi

AU - Jones, Michael E.

AU - Joshu, Corrine E.

AU - Kaaks, Rudolf

AU - Krogh, Vittorio

AU - Kühn, Tilman

AU - Kvaskoff, Marina

AU - Lee, I. Min

AU - Mahamat-Saleh, Yahya

AU - Malm, Johan

AU - Manjer, Jonas

AU - Maskarinec, Gertraud

AU - Millen, Amy E.

AU - Mukhtar, Toqir K.

AU - Neuhouser, Marian L.

AU - Robsahm, Trude E.

AU - Schoemaker, Minouk J.

AU - Sieri, Sabina

AU - Sund, Malin

AU - Swerdlow, Anthony J.

AU - Thomson, Cynthia A.

AU - Ursin, Giske

AU - Wactawski-Wende, Jean

AU - Wang, Ying

AU - Wilkens, Lynne R.

AU - Wu, Yujie

AU - Zoltick, Emilie

AU - Willett, Walter C.

AU - Smith-Warner, Stephanie A.

AU - Ziegler, Regina G.

PY - 2023/1

Y1 - 2023/1

N2 - Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42–68) years at blood collection and 63 (49–75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, calibrated to this assay to permit using a common metric. Study-specific relative risks (RRs) for season-standardized 25(OH)D concentrations were estimated by conditional logistic regression and combined by random-effects models. Circulating 25(OH)D increased from a median of 22.6 nmol/L in consortium-wide decile 1 to 93.2 nmol/L in decile 10. Breast cancer risk in each decile was not statistically significantly different from risk in decile 5 in models adjusted for breast cancer risk factors, and no trend was apparent (P-trend = 0.64). Compared to women with sufficient 25(OH)D based on Institute of Medicine guidelines (50– < 62.5 nmol/L), RRs were not statistically significantly different at either low concentrations (< 20 nmol/L, 3% of controls) or high concentrations (100– < 125 nmol/L, 3% of controls; ≥ 125 nmol/L, 0.7% of controls). RR per 25 nmol/L increase in 25(OH)D was 0.99 [95% confidence intervaI (CI) 0.95–1.03]. Associations remained null across subgroups, including those defined by body mass index, physical activity, latitude, and season of blood collection. Although none of the associations by tumor characteristics reached statistical significance, suggestive inverse associations were seen for distant and triple negative tumors. Circulating 25(OH)D, comparably measured in 17 international cohorts and season-standardized, was not related to subsequent incidence of invasive breast cancer over a broad range in vitamin D status.

AB - Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42–68) years at blood collection and 63 (49–75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, calibrated to this assay to permit using a common metric. Study-specific relative risks (RRs) for season-standardized 25(OH)D concentrations were estimated by conditional logistic regression and combined by random-effects models. Circulating 25(OH)D increased from a median of 22.6 nmol/L in consortium-wide decile 1 to 93.2 nmol/L in decile 10. Breast cancer risk in each decile was not statistically significantly different from risk in decile 5 in models adjusted for breast cancer risk factors, and no trend was apparent (P-trend = 0.64). Compared to women with sufficient 25(OH)D based on Institute of Medicine guidelines (50– < 62.5 nmol/L), RRs were not statistically significantly different at either low concentrations (< 20 nmol/L, 3% of controls) or high concentrations (100– < 125 nmol/L, 3% of controls; ≥ 125 nmol/L, 0.7% of controls). RR per 25 nmol/L increase in 25(OH)D was 0.99 [95% confidence intervaI (CI) 0.95–1.03]. Associations remained null across subgroups, including those defined by body mass index, physical activity, latitude, and season of blood collection. Although none of the associations by tumor characteristics reached statistical significance, suggestive inverse associations were seen for distant and triple negative tumors. Circulating 25(OH)D, comparably measured in 17 international cohorts and season-standardized, was not related to subsequent incidence of invasive breast cancer over a broad range in vitamin D status.

KW - 25-Hydroxyvitamin D

KW - Biomarker

KW - Breast cancer

KW - Calibration

KW - Pooled analysis

KW - Prospective cohort study

KW - Vitamin D

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M3 - Article

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SN - 0393-2990

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JO - European Journal of Epidemiology

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Circulating vitamin D and breast cancer risk: an international pooling project of 17 cohorts

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