AS383 - Circulating Vitamin D Levels and Risk of Breast and Colorectal Cancer: a Pooled Analysis

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Investigator Names and Contact Information

Stephanie A. Smith-Warner [​swarner@hsph.harvard.edu ]

 

Introduction/Intent

Previous epidemiologic and experimental data suggest that vitamin D may be associated with reduced cancer risk, with the evidence strongest for breast and colorectal cancer. However, for both cancer sites, the dose-response relationship is unclear; associations among population subgroups and by tumor characteristics have not been evaluated thoroughly; and confounding by associated lifestyle factors has not always been addressed adequately. We are conducting a prospective pooled analysis of the association between circulating 25-hydroxyvitamin D [25(OH)D] levels and risk of breast and colorectal cancer within a consortium of 19 cohort studies, including >9500 breast cancer cases and >7100 colorectal cancer cases. Inclusion criteria for participation in the consortium are that a study collected blood samples prospectively and had at least 50 cases of the specific cancer being analyzed. For studies that had previously measured 25(OH)D levels in a breast and/or colorectal cancer nested case-control dataset, such as the Women’s Health Initiative,1 we are requesting that a 150 µL frozen aliquot of serum be assayed at Heartland Assays for 29 of the control participants from each previously conducted case-control study.  These repeat assays will be used to calibrate the previously measured 25(OH)D values with the new assay data currently being obtained at Heartland Assays for this project.  We are also asking each participating cohort for an extensive set of covariate, as well as cancer histology, data.  We will analyze the primary data from each study and then pool the study-specific estimates using a random effects model.  Absolute 25(OH)D values, as well as cohort-specific quantiles, will be used to facilitate generating broadly applicable results.  These analyses will provide powerful insights into the relation between vitamin D and breast and colorectal cancer risk and have the potential to inform recommendations regarding sun exposure and vitamin D intake requirements.

Specific Aims

We propose to analyze the primary data in this consortium of 19 cohort studies to examine the following hypotheses:

  1. Higher levels of circulating 25(OH)D levels are associated with a reduced risk of colorectal cancer.
    1. The association is stronger among leaner individuals, among more physically active individuals, and among individuals with higher circulating insulin-like growth factor-I (IGF-1) levels.
    2. The association is stronger among individuals with high calcium intake.
    3. The association is stronger for rectal cancer. 
    4. The association varies with common genetic variation in VDR.
  2. Higher levels of circulating 25(OH)D levels are associated with a reduced risk of breast cancer.
    1. The association is stronger among older women, among leaner women, among more physically active women, and among women with higher circulating IGF-I levels.
    2. The association is stronger among individuals with high calcium intake.
    3. The association will be apparent among both estrogen receptor (ER) and progesterone receptor (PR) positive (ER+/PR+) and ER-/PR- tumors.
    4. The association varies with common genetic variation in VDR.