Abstract 4633: Circulating vitamin D and breast cancer risk: Repeated exposure assessment and 18 years of follow-up in the Nurses’ Health Study
Authors: Eliassen A. Heather , Tworoger Shelley S. , Bertone-Johnson Elizabeth , Rosner Bernard , Willett Walter C. , Hankinson Susan E. 
Published: June 2012

Abstract
In animals vitamin D reduces proliferation and promotes differentiation and apoptosis. Given these mechanisms, vitamin D may act both early and late in mammary carcinogenesis. Diet and sun exposure are sources of vitamin D, and plasma 25(OH)D levels are considered the best measure of vitamin D status. To examine the timing of exposure assessment, we conducted a nested case-control study within the prospective Nurses’ Health Study with plasma 25(OH)D levels collected 10 years apart and breast cancer risk. In 1989-90 32,826 women gave a blood sample; 18,743 women gave a second sample in 2000. 25(OH)D was measured in the 1990 sample for women diagnosed 1990-2000 and their matched controls, and in the 1990 and 2000 (when available) samples for women diagnosed 2000-08 and their matched controls. A total of 1,397 invasive breast cancer cases and 1,397 matched controls were included, with two blood samples assayed for 393 cases and their matched controls. Multivariate relative risks (RR) and 95% confidence intervals (CI) were calculated by conditional logistic regression, adjusting for several breast cancer risk factors. We investigated the issue of timing by assessing 1990 and 2000 levels separately and together by cross-classifying (at the median) and modeling the two measures simultaneously. 25(OH)D levels were moderately correlated over 10 years (intra-class correlation coefficient=0.52). Overall, 25(OH)D levels were modestly inversely associated with breast cancer risk (1990 25(OH)D levels over the 18-year follow-up, top vs. bottom quartile RR=0.81, 95% CI (0.64-1.03), p-trend=0.03). Results were similar using proximate 25(OH)D (1990 blood for 1990-2000 follow-up, 2000 blood for 2000-08 follow-up) (RR=0.80, 95% CI (0.62-1.04), p-trend=0.04). Over 2000-08 follow-up, when modeled separately, 1990 levels were significantly inverse (RR=0.62, 95% CI (0.39-0.97), p-trend=0.02) and 2000 levels were suggestively inverse (RR=0.68, 95% CI (0.43-1.07), p-trend=0.11). Cross-classified levels suggest earlier measures may be more important (e.g., compared to low at both times, high 1990 and low 2000 RR=0.56, 95% CI (0.33-0.97), low 1990 and high 2000 RR=0.94, 95% CI (0.62-1.43) and high at both time points RR=0.69, 95% CI (0.47-1.00)). When modeled simultaneously, 1990 25(OH)D levels were inversely associated with breast cancer risk (top vs. bottom quartile RR=0.79, 95% CI (0.61-1.03), p-trend=0.04) while the point estimate was similar but no significant trend was observed with 2000 25(OH)D levels (RR=0.85, 95% CI (0.59-1.22), p-trend=0.38). Planned future analyses include imputing 2000 25(OH)D levels for those without a second blood measure and stratifying by tumor characteristics and lifestyle factors. Overall, these data support a beneficial effect of vitamin D on breast cancer risk and suggest that vitamin D status may be important many years prior to diagnosis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4633. doi:10.1158/1538-7445.AM2011-4633