Calcium intake and prostate cancer among African Americans: Effect modification by vitamin D receptor calcium absorption genotype


  • Glovioell W Rowland,

    1. Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA
    Search for more papers by this author
  • Gary G Schwartz,

    1. Departments of Cancer Biology, Urology, and Epidemiology and Prevention, Wake Forest University, Winston-Salem, NC, USA
    Search for more papers by this author
  • Esther M John,

    1. Cancer Prevention Institute of California, Fremont, CA, USA
    2. Department of Health Research and Policy, Stanford University School of Medicine and Stanford Cancer Institute, Stanford, CA, USA
    Search for more papers by this author
  • Sue Ann Ingles

    Corresponding author
    1. Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA
    • USC/Norris Comprehensive Cancer Center, Department of Preventive Medicine, Keck School of Medicine, Uniersity of Southern California, 1441 Eastlake Avenue, MS 9175, 12113 Braddock Drive, Los Angeles, CA, USA.
    Search for more papers by this author


High dietary intake of calcium has been classified as a probable cause of prostate cancer, although the mechanism underlying the association between dietary calcium and prostate cancer risk is unclear. The vitamin D receptor (VDR) is a key regulator of calcium absorption. In the small intestine, VDR expression is regulated by the CDX-2 transcription factor, which binds a polymorphic site in the VDR gene promoter. We examined VDR Cdx2 genotype and calcium intake, assessed by a food frequency questionnaire, in 533 African–American prostate cancer cases (256 with advanced stage at diagnosis, 277 with localized stage) and 250 African–American controls who participated in the California Collaborative Prostate Cancer Study. We examined the effects of genotype, calcium intake, and diet–gene interactions by conditional logistic regression. Compared with men in the lowest quartile of calcium intake, men in the highest quartile had an approximately twofold increased risk of localized and advanced prostate cancer (odds ratio [OR] = 2.20, 95% confidence interval [CI] = 1.40, 3.46), with a significant dose–response. Poor absorbers of calcium (VDR Cdx2 GG genotype) had a significantly lower risk of advanced prostate cancer (OR = 0.41, 95% CI = 0.19, 0.90). The gene–calcium interaction was statistically significant (p = 0.03). Among men with calcium intake below the median (680 mg/day), carriers of the G allele had an approximately 50% decreased risk compared with men with the AA genotype. These findings suggest a link between prostate cancer risk and high intestinal absorption of calcium. © 2012 American Society for Bone and Mineral Research