Mendelian randomization study finds low vitamin D status increases risk of ovarian cancer

Posted on: September 16, 2016   by  Amber Tovey

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Approximately 20,000 women develop ovarian cancer each year in the United States. Ovarian cancer is the ninth most common cancer among women, and the fifth leading cause of cancer mortality.

Serous epithelial ovarian cancer is the most common form of ovarian cancer. Ovarian serous carcinomas are categorized based upon their rate of progression to invasive carcinoma. Low grade serous carcinomas spread at a lower rate and have a better survival rate than high grade.

In recent years, research has shown that vitamin D may play a role in cancer through its ability to promote cellular differentiation, reduce cancer cell growth, elicit cell death and decrease the formation of tumor blood vessels. However, observational studies have produced conflicting results regarding the relationship between vitamin D and ovarian cancer.

Observational study designs are prone to the influence of confounding factors and reverse causation. For this reason, researchers recently conducted a Mendelian randomization study, a very strong study design that has the ability to prove causation.

Mendelian randomization limits bias by evaluating genetic variants associated with the exposure of interest. In this study, the researchers examined the presence of three genetic variants that are largely associated with vitamin D status among 10,065 individuals with ovarian cancer and 21,654 individuals without ovarian cancer.

The researchers wanted to determine whether those who are genetically prone to a low vitamin D status have higher odds of developing ovarian cancer. They found that for every 8 ng/ml decrease in vitamin D status, women faced 1.27 times greater odds of having ovarian cancer.

 

The study also determined that low vitamin D status had an even more profound effect on the odds of developing high grade serous epithelial ovarian cancer. Per every 8 ng/ml decrease in vitamin D status, women developed high grade serous ovarian cancer 1.54 times more often per every 8 ng/ml decrease in vitamin D status.

The researchers stated,

“In conclusion, we demonstrate an association between low 25(OH)D concentration and risk of ovarian cancer in women of European ancestry, with our MR approach providing estimates which are unaffected by the confounding or biases present in the observational studies.”

They went on to state,

“Here, for the first time, we demonstrate that, for epithelial ovarian cancer, there is a causal effect of low 25(OH)D) concentrations on risk.”

This study consisted of several strengths and a few limitations to consider. The genetic variants used in the study are well known for their role in vitamin D metabolism and bioavailability. Mendelian randomization studies are able to analyze the effects of long term low or high vitamin D status as genetic variants do not change throughout life. Though, one can interfere with their genetic predisposition with vitamin D supplementation and sun exposure. Since the study consisted of such a large sample size, this likely did not affect the results.

Citation

Tovey, A. & Cannell, JJ. Mendelian randomization study finds low vitamin D status may increase risk of ovarian cancer. The Vitamin D Council Blog & Newsletter, 2016.

Source

Ong J. Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study. International Journal of Epidemiology Advance, 2016.

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