TY - JOUR
T1 - Prediagnostic Serum Vitamin D, Vitamin D Binding Protein Isoforms, and Cancer Survival
AU - Weinstein, Stephanie J.
AU - Mondul, Alison M.
AU - Layne, Tracy M.
AU - Yu, Kai
AU - Huang, Jiaqi
AU - Stolzenberg-Solomon, Rachael Z.
AU - Ziegler, Regina G.
AU - Purdue, Mark P.
AU - Huang, Wen Yi
AU - Abnet, Christian C.
AU - Freedman, Neal D.
AU - Albanes, Demetrius
N1 - Publisher Copyright:
© 2022 Published by Oxford University Press. This work is written by US Government employees and is in the public domain in the US.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - Background: Higher circulating vitamin D has been associated with improved overall cancer survival, but data for organ-specific cancers are mixed. Methods: We examined the association between prediagnostic serum 25-hydroxyvitamin D [25(OH)D], the recognized biomarker of vitamin D status, and cancer survival in 4038 men and women diagnosed with 1 of 11 malignancies during 22 years of follow-up (median = 15.6 years) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Multivariable-adjusted proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations between baseline 25(OH)D concentration and subsequent cancer survival; we also stratified on the common vitamin D binding protein isoforms (Gc1f, Gc1s, and Gc2) defined by two single-nucleotide polymorphisms (rs7041 and rs4588) in the vitamin D binding protein gene GC. All P values were 2-sided. Results: Higher 25(OH)D concentrations were associated with greater overall cancer survival (HR for cancer mortality = 0.83, 95% CI = 0.70 to 0.98 for highest vs lowest quintile; Ptrend =. 05) and lung cancer survival (HR = 0.63, 95% CI = 0.44 to 0.90; Ptrend =. 03). These associations were limited to cases expressing the Gc2 isoform (HR = 0.38 for Gc2-2, 95% CI = 0.14 to 1.05 for highest vs lowest quintile; Ptrend =. 02; and HR = 0.30 for Gc1-2/Gc2-2 combined, 95% CI = 0.16 to 0.56; Ptrend <. 001 for overall and lung cancer, respectively). Conclusions: Higher circulating 25(OH)D was associated with improved overall and lung cancer survival. As this was especially evident among cases with the genetically determined Gc2 isoform of vitamin D binding protein, such individuals may gain a cancer survival advantage by maintaining higher 25(OH)D blood concentrations.
AB - Background: Higher circulating vitamin D has been associated with improved overall cancer survival, but data for organ-specific cancers are mixed. Methods: We examined the association between prediagnostic serum 25-hydroxyvitamin D [25(OH)D], the recognized biomarker of vitamin D status, and cancer survival in 4038 men and women diagnosed with 1 of 11 malignancies during 22 years of follow-up (median = 15.6 years) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Multivariable-adjusted proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations between baseline 25(OH)D concentration and subsequent cancer survival; we also stratified on the common vitamin D binding protein isoforms (Gc1f, Gc1s, and Gc2) defined by two single-nucleotide polymorphisms (rs7041 and rs4588) in the vitamin D binding protein gene GC. All P values were 2-sided. Results: Higher 25(OH)D concentrations were associated with greater overall cancer survival (HR for cancer mortality = 0.83, 95% CI = 0.70 to 0.98 for highest vs lowest quintile; Ptrend =. 05) and lung cancer survival (HR = 0.63, 95% CI = 0.44 to 0.90; Ptrend =. 03). These associations were limited to cases expressing the Gc2 isoform (HR = 0.38 for Gc2-2, 95% CI = 0.14 to 1.05 for highest vs lowest quintile; Ptrend =. 02; and HR = 0.30 for Gc1-2/Gc2-2 combined, 95% CI = 0.16 to 0.56; Ptrend <. 001 for overall and lung cancer, respectively). Conclusions: Higher circulating 25(OH)D was associated with improved overall and lung cancer survival. As this was especially evident among cases with the genetically determined Gc2 isoform of vitamin D binding protein, such individuals may gain a cancer survival advantage by maintaining higher 25(OH)D blood concentrations.
UR - http://www.scopus.com/inward/record.url?scp=85136910679&partnerID=8YFLogxK
U2 - 10.1093/jncics/pkac019
DO - 10.1093/jncics/pkac019
M3 - Article
C2 - 35603848
AN - SCOPUS:85136910679
SN - 2515-5091
VL - 6
JO - JNCI Cancer Spectrum
JF - JNCI Cancer Spectrum
IS - 2
M1 - pkac019
ER -