Vitamin D-associated genetic variation and risk of breast cancer in the breast and prostate cancer cohort consortium (BPC3)

Alison M Mondul¹, Irene M Shui², Kai Yu³, Stephanie J Weinstein³, Konstantinos K Tsilidis⁴, Amit D Joshi², Antonio Agudo⁵, Christine D Berg⁶, Amanda Black³, Julie E Buring⁷, Daniel I Chasman⁷, Mia M Gaudet⁸, Christopher Haiman⁹, Susan E Hankinson¹⁰, Brian E Henderson⁹, Robert N Hoover³, David J Hunter², Kay-Tee Khaw¹¹, Tilman Kühn¹², Marina Kvaskoff¹³, Loic Le Marchand¹⁴, Sara Lindström², Marjorie L McCullough⁸, Kim Overvad¹⁵, Petra H Peeters¹⁶, Elio Riboli¹⁷, Paul M Ridker⁷, Daniel O Stram⁹, Malin Sund¹⁸, Dimitrios Trichopoulos¹⁹, Rosario Tumino²⁰, Elisabete Weiderpass²¹, Walter Willett²², Peter Kraft², Regina G Ziegler³, Demetrius Albanes³

Affiliations

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland. amondul@umich.edu.
² Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland.
⁴ Nuffield Department of Clinical Medicine, Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom. Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
⁵ Unit of Nutrition, Environment, and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
⁶ Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, Maryland.
⁷ Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
⁸ Epidemiology Research Program, American Cancer Society, Atlanta, Georgia.
⁹ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
¹⁰ Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Department of Epidemiology, University of Massachusetts, Amherst School of Public Health and Health Sciences, Amherst, Massachusetts. Cancer Research Center, Brigham and Women's Hospital, Boston, Massachusetts.
¹¹ Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.
¹² Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
¹³ Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
¹⁴ Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
¹⁵ Department of Public Health Section for Epidemiology, Aarhus University, Aarhus, Denmark.
¹⁶ Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands.
¹⁷ Department of Epidemiology and Biostatistics, Imperial College School of Public Health, London, United Kingdom.
¹⁸ Department of Surgical and Perioperative Sciences, Umea University, Umea, Sweden.
¹⁹ Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. Hellenic Health Foundation, Athens, Greece.
²⁰ Cancer Registry and Histopathology Unit, "Civic-M.P. Arezzo" Hospital, ASP Ragusa, Italy.
²¹ Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland.
²² Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.

PMID: 25542828
PMCID: PMC4355227
DOI: 10.1158/1055-9965.EPI-14-1127

Vitamin D-associated genetic variation and risk of breast cancer in the breast and prostate cancer cohort consortium (BPC3)

Alison M Mondul et al. Cancer Epidemiol Biomarkers Prev. 2015 Mar.

. 2015 Mar;24(3):627-30.

doi: 10.1158/1055-9965.EPI-14-1127. Epub 2014 Dec 26.

Authors

Affiliations

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland. amondul@umich.edu.
² Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland.
⁴ Nuffield Department of Clinical Medicine, Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom. Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
⁵ Unit of Nutrition, Environment, and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
⁶ Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, Maryland.
⁷ Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
⁸ Epidemiology Research Program, American Cancer Society, Atlanta, Georgia.
⁹ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
¹⁰ Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Department of Epidemiology, University of Massachusetts, Amherst School of Public Health and Health Sciences, Amherst, Massachusetts. Cancer Research Center, Brigham and Women's Hospital, Boston, Massachusetts.
¹¹ Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.
¹² Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
¹³ Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
¹⁴ Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
¹⁵ Department of Public Health Section for Epidemiology, Aarhus University, Aarhus, Denmark.
¹⁶ Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands.
¹⁷ Department of Epidemiology and Biostatistics, Imperial College School of Public Health, London, United Kingdom.
¹⁸ Department of Surgical and Perioperative Sciences, Umea University, Umea, Sweden.
¹⁹ Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. Hellenic Health Foundation, Athens, Greece.
²⁰ Cancer Registry and Histopathology Unit, "Civic-M.P. Arezzo" Hospital, ASP Ragusa, Italy.
²¹ Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland.
²² Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.

PMID: 25542828
PMCID: PMC4355227
DOI: 10.1158/1055-9965.EPI-14-1127

Abstract

Background: Two recent genome-wide association studies (GWAS) identified SNPs in or near four genes related to circulating 25-hydroxyvitamin D [25(OH)D] concentration. To examine the hypothesized inverse relationship between vitamin D status and breast cancer, we studied the associations between SNPs in these genes and breast cancer risk in a large pooled study of 9,456 cases and 10,816 controls from six cohorts.

Methods: SNP markers localized to each of four genes (GC, CYP24A1, CYP2R1, and DHCR7) previously associated with 25(OH)D were genotyped and examined both individually and as a 4-SNP polygenic score. Logistic regression was used to estimate the associations between the genetic variants and risk of breast cancer.

Results: We found no association between any of the four SNPs or their polygenic score and breast cancer risk.

Conclusions: Our findings do not support an association between vitamin D status, as reflected by 25(OH)D-related genotypes, and breast cancer risk.

Impact: These findings may contribute to future meta-analyses and scientific review articles, and provide new data about the association between vitamin D-related genes and breast cancer. Cancer Epidemiol Biomarkers Prev; 24(3); 627-30. ©2014 AACR.

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Conflict of interest statement

Conflict of Interest: The authors have no conflicts to disclose.

Figures

**Figure 1**
Association Between the 4-SNP Polygenic Score and Risk of Breast Cancer

See this image and copyright information in PMC

References

1. Wang D, Velez de-la-Paz OI, Zhai JX, Liu DW. Serum 25-hydroxyvitamin D and breast cancer risk: a meta-analysis of prospective studies. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2013;34:3509–17. - PubMed
1. Ahn J, Yu K, Stolzenberg-Solomon R, Simon KC, McCullough ML, Gallicchio L, et al. Genome-wide association study of circulating vitamin D levels. Hum Mol Genet. 19:2739–45. - PMC - PubMed
1. Wang TJ, Zhang F, Richards JB, Kestenbaum B, van Meurs JB, Berry D, et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 376:180–8. - PMC - PubMed
1. Hiraki LT, Major JM, Chen C, Cornelis MC, Hunter DJ, Rimm EB, et al. Exploring the Genetic Architecture of Circulating 25-Hydroxyvitamin D. Genetic Epidemiology. 2012 - PMC - PubMed
1. Hunter DJ, Riboli E, Haiman CA, Albanes D, Altshuler D, Chanock SJ, et al. A candidate gene approach to searching for low-penetrance breast and prostate cancer genes. Nat Rev Cancer. 2005;5:977–85. - PubMed

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Vitamin D-associated genetic variation and risk of breast cancer in the breast and prostate cancer cohort consortium (BPC3)

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Vitamin D-associated genetic variation and risk of breast cancer in the breast and prostate cancer cohort consortium (BPC3)

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Conflict of interest statement

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