Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 15 No.
5 • September 2012
Overexpression of Gene Encoding Vitamin D3 Breakdown is An Independent Marker of Poorer Survival in Lung Cancer Patients
A recent paper studied the relationship of the expression of CYP24A1, the gene that encodes the main metabolizing enzyme of 1,25-D3 (calcitriol, the active form of vitamin D3) and the likelihood of survival in human lung cancer patients.
The researchers found that CYP24A1 mRNA was elevated 8- to 50-fold in lung adenocarcinoma (the most common form of lung cancer). Adenocarcinoma accounts for over 50% of all non- small cell lung cancers. Sadly, at least 60% of patients with lung adenocarcinoma are discovered to have the disease at an advanced stage III/IV metastatic disease.
The results of this study showed that, “[a]t 5 years of follow-up, the probability of survival was 42% (high CYP24A1, n=29) versus 81% (low CYP24A1, n=57)(P=0.007). The validation set of 101 tumors showed that CYP24A1 was independently prognostic of survival (multivariate Cox model adjusted for age, gender, and stage, P=0.001).” The authors concluded that, “CYP24A1 overexpression is associated with poorer survival in lung AC [adenocarcinoma]. This may relate to abrogation of antiproliferative effects of 1,25-D3 in high CYP24A1 expressing lung AC.” Indeed, “the cell lines with high expression of CYP24A1 (example A549) exhibited the lowest expression of VDR [vitamin D receptor] mRNA; the converse was observed with SKLU-1 [a different cell line].”
The researchers mention that overexpression of CYP24A1 has also been observed in colon, cervical, ovarian, cutaneous squamous cell, and esophageal carcinomas. They also note that findings concerning CYP24A1 have led to research to find new vitamin D analogues (because very high doses of vitamin D can cause hypercalcemia, excessive calcium levels) and specific CYP24A1 inhibitors.
We suggest that Vitamin D3 supplementation at levels unlikely to cause hypercalcemia (we recommend 2000–4000 IU/day, though the two of us take 6000–8000 IU/day). may be a way to help prevent the development of lung cancer adenocarcinoma. It will be helpful, of course, when it is possible for individuals to have their CYP24A1 expression measured to help predict the outcome and need for aggressive therapies (if they already have lung cancer) or to assess the likelihood of getting it in the first place. In order to make genetic testing available on a widespread basis to those who desire to and are able to purchase it, the FDA’s blockades to such access will have to be eliminated.
- Chen et al. CYP24A1 is an independent prognostic marker of survival in patients with lung adenocarcinoma. Clin Cancer Res 17(4):817-26 (2010).