Stephanie Weinstein

Ph.D

NCI

Staff Scientist

PLCO (Learn more about this study)

PLCO-381

Jul 13, 2018

Prospective Serum Vitamin D Status and Cancer Survival in PLCO

Circulating vitamin D status has been extensively studied in relation to cancer risk in the PLCO and ATBC cohorts. In terms of cancer survival, we recently completed an analysis of serum 25-hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, and survival after a cancer diagnosis in ATBC (European Journal of Epidemiology, in press). Among 4,616 cancer cases with previously measured serum 25(OH)D, we found that higher 25(OH)D was associated with lower overall cancer mortality (HR=0.76, 95% CI 0.67-0.85 for highest vs. lowest quintile, p-trend <0.0001) and lower mortality from the following site-specific malignancies: prostate (HR=0.74, 95% CI 0.55-1.01, p-trend=0.005), kidney (HR=0.59, 95% CI 0.35-0.98, p-trend=0.28), and melanoma (HR=0.39, 95% CI 0.20-0.78, p-trend=0.01), but increased mortality from lung cancer (HR=1.28, 95% CI 1.02-1.61, p-trend=0.19). Improved survival was also suggested for head and neck, gastric, pancreatic, and liver cancers, though risks were not statistically significant. Other literature is supportive of some of these findings.

We would like to conduct a similar all cancer analysis in PLCO using extant 25(OH)D data in the following datasets: colorectum (n=476 cases)[1], prostate (n=749)[2] and (n=226)[3], bladder (n=375)[4], kidney (n=161)[5], NHL (n=286)[6], upper GI (n=99)[7], pancreas (n=183)[8], ovary (n=74)[9], endometrial(n=147)[10], and breast (n=1005)[11]. The total case number would be 3,781 cases. (PI’s of these original risk analyses will be invited to participate in the present analysis.)

Because the assay methods and dates of analysis differ among the various sites, we will create separate 25(OH)D categories based on the 25(OH)D distribution within each of these sets [kidney, NHL, upper GI, ovary and endometrial were conducted together as part of our Vitamin D Pooling Project of Rarer Cancers (published in 2010) and will be treated as one set]. In addition, because of the known seasonal variation in 25(OH)D concentrations, the 25(OH)D categories will also be created separately for two seasons, "darker” and “sunnier”, with definitions previously as defined for PLCO. Therefore, 25(OH)D will be modeled using season- and set-specific quantiles based on the 25(OH)D distribution of all subjects in each season and set, and entered into multi-variable Cox models as indicator variables.

1. Weinstein SJ, et al. Int J Cancer 136 (6):E654-664, 2015.
2. Ahn J, et al J Natl Cancer Inst 100 (11):796-804, 2008.
3. Layne TM, et al. Cancer 123 (14):2698-2704, 2017.
4. Mondul AM, et al. Cancer Epidemiol Biomarkers Prev 21 (7):1222-1225, 2012.
5. Gallicchio L, et al., Am J Epidemiol 172 (1):47-57, 2010.
6. Purdue MP, et al. Am J Epidemiol 172 (1):58-69, 2010.
7. Abnet CC, et al. Am J Epidemiol 172 (1):94-106, 2010.
8. Stolzenberg-Solomon RZ, et al. Cancer Res 69 (4):1439-1447, 2009.
9. Zheng W, et al. Am J Epidemiol 172 (1):70-80, 2010.
10. Zeleniuch-Jacquotte A, et al. Am J Epidemiol 172 (1):36-46, 2010.
11. Freedman DM, et al. Cancer Epidemiol Biomarkers Prev 17 (4):889-894, 2010.

Primary Aims

1. To examine the association between pre-diagnostic circulating 25(OH)D and survival after a cancer diagnosis.

2. To examine the association between pre-diagnostic circulating 25(OH)D and cancer site-specific survival.

Secondary Aims

1. To examine the association between pre-diagnostic circulating 25(OH)D and overall and cancer site-specific survival by cancer stage at diagnosis.

2. To examine the association between pre-diagnostic circulating 25(OH)D and overall cancer survival by treatment modality.

Alison Mondul, University of Michigan SPH;
Tracy Layne, NCI;
Demetrius Albanes, NCI

(Please note that the system is pulling in my married name "Oshinsky" but I use "Weinstein" professionally.)