U-M researchers find high levels of enzyme that blocks vitamin D can predict lung cancer survival
ANN ARBOR, Mich. — 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.
NOTE: Current 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.
Lung cancer statistics: 222,520 Americans will be diagnosed with lung cancer this year and 157,300 will die from the disease, making it the biggest cancer killer, according to the American Cancer Society
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: National Institutes of Health
Reference: Clinical Cancer Research, Vol. 17, No. 4, pp. 817-826
U-M Cancer AnswerLine, 800-865-1125
U-M Comprehensive Cancer Center