Abstract 725: Biomarkers of circulating vitamin D status and expression of tumor molecular markers Ki67, p53, and COX2 among colorectal cancer cases in the Southern Community Cohort Study
Authors: Lawler Thomas , Su Timothy , Cai Qiuyin , Steinwandel Mark , Zheng Wei , Blot William J. , Andersen Shaneda Warren 
Published: June 2022

Introduction: Epidemiologic studies and controlled trials provide evidence that higher 25-hydroxyvitaminD is associated with improved survival in colorectal cancer (CRC), although there are limited data in African Americans (AAs), who are at greater risk for CRC mortality and vitamin D deficiency. Herein, we report associations between vitamin D serum biomarkers collected at cohort entry up to 15 years prior to CRC onset and CRC tumor subtypes defined by high expression of tumor markers (Ki67, p53, and COX2) that represent cellular processes (proliferation, apoptosis, and inflammation) affected by vitamin D. Importantly, higher expression of these markers reflects greater risk for metastasis and CRC-specific mortality.

Methods: Data arise from the Southern Community Cohort Study, a cohort from the southeastern United States where the majority of participants are AA. Incident CRC cases with tumor sample were analyzed (n=104). Expression of cellular Ki67, p53, and COX2 (% positivity) were measured and categorized by literature-defined high vs. low cut-points (20%, 10%, and 20%, respectively). Logistic models adjusted for age, race, and sex were used to measure associations between vitamin D biomarkers: 25-hydroxyvitaminD, vitamin D binding protein (VDBP), and calculated free 25-hydroxyvitaminD (vitamin D not bound by VDBP) and the odds of a more aggressive tumor subtype, defined by higher cellular expression. Associations were assessed in the full sample and the subsample of AAs (n=70).

Results: There were 52 tumors with high Ki67 expression, 37 with high p53, and 50 with high COX2. Fifteen tumors had high expression of all three markers. Cases were 55.8±0.4 (mean±SE) years at enrollment (range 40-79). The median 25-hydroxyvitaminD was lower in cases with high p53 expressing tumors compared to low expression (13.5 vs. 18.0 ng/mL, respectively, p = .03). Median values for other biomarkers were similar by tumor subtype (p &gt .05). 25-hydroxyvitaminD was not associated with having a tumor with high Ki67 expression (odds ratio (OR) per 1 SD increase [95% CI] = 1.29 [0.85-1.95], p-trend = .23), high p53 expression (0.80 [0.52-1.23], p-trend = .30), or high COX2 expression (1.29 [0.83-2.00], p = .25). We observed null associations for VDBP, and free 25-hydroxyvitaminD with all tumor subtypes. Results were similar in AAs, although higher VDBP was associated with lower odds of high Ki67 tumors (0.45 [0.21-0.97], p-trend = .04 per 1 SD increase).

Conclusion: In this sample of predominantly AA CRC cases, we observed no association between vitamin D biomarkers in stored serum and subsequent more aggressive CRC molecular subtypes. More work is needed to characterize the relationship between vitamin D and expression of CRC tumor markers, which may help clarify the protective role of maintaining adequate vitamin D levels in association with CRC.

Citation Format: Thomas Lawler, Timothy Su, Qiuyin Cai, Mark Steinwandel, Wei Zheng, William J. Blot, Shaneda Warren Andersen. Biomarkers of circulating vitamin D status and expression of tumor molecular markers Ki67, p53, and COX2 among colorectal cancer cases in the Southern Community Cohort Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 725.