High levels of the enzyme that blocks
vitamin D can predict lung cancer survival
Recent research suggests vitamin D may be able to stop
or prevent cancer. Now, a new study finds an enzyme that plays a role in metabolizing
vitamin D can predict lung cancer survival.
The study, from researchers at the University of Michigan Comprehensive Cancer
Center, suggests that this enzyme stops the anti-cancer effects of vitamin D.
Levels of the enzyme, called CYP24A1, were elevated as much as 50 times in
lung adenocarcinoma compared with normal lung tissue. The higher the level of
CYP24A1, the more likely tumors were to be aggressive. About a third of lung cancer
patients had high levels of the enzyme. After five years, those patients had nearly
half the survival rate as patients with low levels of the enzyme.
Researchers then linked this to how CYP24A1 interacts with calcitriol, the
active form of vitamin D. CYP24A1 breaks down calcitriol, which has a normal and
crucial role when kept in check. But when levels of CYP24A1 climb, the enzyme
begins to hinder the positive anti-cancer effects of vitamin D.
Results of the study appear in Clinical Cancer Research.
Previous studies have linked low levels of vitamin D to a higher incidence
of cancer and worse survival. Researchers are looking at using vitamin D to help
prevent lung cancer from returning and spreading after surgery. This new study
suggests the possibility of using CYP24A1 levels to personalize this approach
to those likely to benefit most.
"Half of lung cancers will recur after surgery, so it's important to find
a way to prevent or delay this recurrence. A natural compound like vitamin D is
attractive because it has few side effects, but it's even better if we can determine
exactly who would benefit from receiving vitamin D," says study author Nithya
Ramnath, M.D., associate professor of internal medicine at the U-M Medical School.
Researchers also are working to identify drugs that block CYP24A1. Blocking
the enzyme would reinstate the positive anti-cancer effects of vitamin D, suggesting
that this inhibitor could potentially be combined with vitamin D treatments.
Current US recommendations call for 600-800 IU of vitamin D daily, depending
on age. Studies looking at vitamin D in lung cancer are testing medically administered
doses 200 times what could be taken by mouth naturally. Taking large amounts of
vitamin D supplements is not currently recommended to prevent or treat lung cancer.
Additional U-M authors: Guoan Chen, So Hee Kim, Amanda N. King, Lili Zhao,
Robert U. Simpson, Paul J. Christensen, Zhuwen Wang, Dafydd G. Thomas, Thomas
J. Giordano, Lin Lin, Dean E. Brenner, David G. Beer.
Funding was received from the National Institutes of Health.
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