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Genetic variation in vitamin D-related genes and risk of breast cancer among women of European and East Asian descent

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Tumor Biology

Abstract

Studies of vitamin D-related genetic variants and breast cancer have been inconsistent. This study aimed to investigate associations of vitamin D-related polymorphisms and breast cancer risk among European and East Asian women and potential interactions with menopausal status and breast tumour subtypes. Data from a case–control study of breast cancer (1037 cases and 1050 controls) were used to assess relationships between 21 polymorphisms in two vitamin D-related genes (GC and VDR) and breast cancer risk. Odds ratios were calculated in stratified analyses of European and East Asian women, using logistic regression in an additive genetic model. An interaction term was used to explore modification by menopausal status. Polytomous regression was used to assess heterogeneity by breast tumour subtype. False discovery rate adjustments were conducted to account for multiple testing. No association was observed between GC or VDR polymorphisms and breast cancer risk. Modification of these relationships by menopausal status was observed for select polymorphisms in both Europeans (VDR rs4328262 and rs11168292) and East Asians (GC rs7041 and VDR rs11168287). Heterogeneity by tumour subtype was seen for three VDR polymorphisms (rs1544410, rs7967152 and rs2239186) among Europeans, in which associations with ER−/PR−/HER2+ tumours, but not with other subtypes, were observed. In conclusion, associations between vitamin D-related genetic variants and breast cancer were not observed overall, although the relationships between vitamin D pathway polymorphisms and breast cancer may be modified by menopausal status and breast tumour subtype.

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Acknowledgments

The authors thank all participants for their contribution to this research study. We are grateful for the assistance from Dr. Linda Warren, Dr. Philip Switzer, Caroline Speers, the BC Cancer Registry, the Screening Mammography Program of BC, Agnes Bauzon, Alegria Imperial, Betty Hall, Lina Hsu, Maria Andrews, Teresa Pavlin, Dr. Ross Walker, Dr. Ralph George, Celine Morissette, Jane Warner, Hilary Rimmer, Meghan Hamel and Annie Langley with participant recruitment and data collection in Vancouver and Kingston. The authors thank the genotyping services provided by the McGill University and Genome Quebec Innovation Centre, Montreal, Canada.

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Authors and Affiliations

  1. Department of Public Health Sciences and Cancer Research Institute, Queen’s University, Kingston, ON, Canada

    Joy Shi, Harriet Richardson & Kristan J. Aronson

  2. Alberta Cancer Prevention Legacy Fund, Alberta Health Services, Calgary, AB, Canada

    Anne Grundy

  3. Department of Environmental and Occupational Health, Drexel University, Philadelphia, PA, USA

    Igor Burstyn

  4. Canada’s Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada

    Johanna M. Schuetz & Angela Brooks-Wilson

  5. Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada

    Caroline A. Lohrisch

  6. Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON, Canada

    Sandip K. SenGupta

  7. Department of Cancer Control Research, British Columbia Cancer Agency, Vancouver, BC, Canada

    Agnes S. Lai & John J. Spinelli

  8. Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada

    Angela Brooks-Wilson

  9. School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada

    John J. Spinelli

  10. Division of Cancer Care and Epidemiology, Queen’s Cancer Research Institute, 10 Stuart Street, Kingston, ON, K7L 3N6, Canada

    Kristan J. Aronson

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  1. Joy Shi
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  2. Anne Grundy
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Corresponding author

Correspondence to Kristan J. Aronson.

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Funding

The Canadian Breast Cancer Study was supported by the Canadian Institutes of Health Research (Grant #69036).

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Supplementary 1

Table S1 Minor allele frequencies and age- and centre-adjusted odds ratios for the associations between SNPs in vitamin D-related genes and breast cancer risk among South Asian and Mixed/Other subgroups (DOC 64 kb)

Supplementary 2

Table S2 Interactions of menopausal status and SNPs in vitamin D-related genes on breast cancer risk in European and East Asian women (DOC 62 kb)

Supplementary 3

Table S3 Analyses of heterogeneity of odds ratios by ER/PR/HER2-defined tumour subtype for SNPs in vitamin D-related genes among European women (DOC 63 kb)

Supplementary 4

Table S4 Analyses of heterogeneity of odds ratios by ER/PR/HER2-defined tumour subtype for SNPs in vitamin D-related genes among East Asian women (DOC 63 kb)

Supplementary 5

Table S5 Analyses of heterogeneity of odds ratios by ER/PR-defined tumour subtype for SNPs in vitamin D-related genes among European and East Asian women (DOC 66 kb)

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Shi, J., Grundy, A., Richardson, H. et al. Genetic variation in vitamin D-related genes and risk of breast cancer among women of European and East Asian descent. Tumor Biol. 37, 6379–6387 (2016). https://doi.org/10.1007/s13277-015-4417-8

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  • DOI: https://doi.org/10.1007/s13277-015-4417-8

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