High levels of vitamin D are associated with protection against bladder cancer, according to a multidisciplinary study coordinated by molecular biologists and epidemiologists from the Spanish National Cancer Research Centre (CNIO), the conclusions of which are being published today in the Journal of National Cancer Institute (JNCI) .

The study has been led by Núria Malats, head of the Genetic and Molecular Epidemiology Group, and Francisco X. Real, from the Epithelial Carcinogenesis Group, at the CNIO.

The authors of the study took blood samples from more than 2,000 individuals - including patients with bladder cancer and control subjects free from the disease - in 18 Spanish hospitals, making of this the largest study carried out to-date in this field. “We have seen that those subjects with the highest levels of 25(OH)D3, a stable form of vitamin D in the blood, are those who showed the lowest risk of suffering bladder cancer. These results indicate that high levels of this vitamin are associated with protection from the illness or, similarly, that low levels are associated with a higher risk of suffering from it”, says Malats.

“We have also shown, using in vitro molecular analysis, that vitamin D regulates the expression of a protein - FGFR3 - that takes part in the development of bladder cancer”, adds Real.

According to the study, this protective effect is more obvious in those patients with more aggressive cancers. “We observe that high levels of vitamin D diminish, above all, the risk of developing invasive bladder cancer with low levels of FGFR3; which is to say those cancers with the highest probability of metastizing”, says André FS Amaral, first author of the study.

The research results suggest that an increase in the dietary or supplementary intake of this vitamin, or via a controlled increase in sun exposure, might be beneficial for the patient in terms of prevention and treatment.

MORE THAN 11,000 NEW CASES EACH YEAR IN SPAIN

Bladder cancer represents a serious public health problem in many countries, especially Spain, where 11,000 new cases are registered each year, one of the highest rates anywhere in the world. In fact, it is the fourth most frequent type of tumour among Spanish males, after prostate, lung and colorectal cancers.

Following diagnosis, patients are continually observed with different follow-up techniques, among them cystoscopy, which requires the introduction of a small camera via the urethra to observe the bladder lining.

This type of follow-up affects the patients’ quality of life and imposes heavy costs on healthcare authorities, thus further increasing the need to improve prevention strategies faced with this type of cancer.

Recent studies relate vitamin D levels with other types of cancer like breast or colon cancer. Despite this research, it is still not clearly understood which molecular routes are used by this vitamin to exercise its protective effect, or the role it plays in other types of tumours.
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INTERNATIONAL COLLABORATION
The study took place within the EPICURO/Spanish Bladder Cancer Study, whose aims are to evaluate, among other aspects, both the genetic and non-genetic factors associated with the risk and prognosis for this tumour.

The EPICURO/Spanish Bladder Cancer Study began in 1997 as a collaborative project involving several Spanish institutions coordinated by the Instituto Hospital del Mar de Investigaciones Médicas (Barcelona), and the Division of Cancer Epidemiology and Genetics of the US National Cancer Institute.

Researcher Alberto Muñoz, from the CSIC’s Biomedical Research Institute in Madrid has also participated in this specific study on vitamin D.

The research project has been funded by the World Cancer Research Fund (UK); the Intramural Research Program of the National Cancer Institute’s Division of Cancer Epidemiology and Genetics (US); the Fondo de Investigación Sanitaria, the Red Temática de Investigación Cooperativa en Cáncer, the AECC’s Scientific Foundation, the Consolíder ONCOBIO project and the Madrid regional government in Spain.

Reference article:
Plasma 25-hydroxyvitamin D3 and bladder cancer risk according to tumor stage and FGFR3 status. André FS Amaral, Marinela Méndez-Pertuz, Alberto Muñoz, Debra T Silverman, Yves Allory, Manolis Kogevinas, Josep Lloreta, Nathaniel Rothman, Alfredo Carrato, Manuel Rivas del Fresno, Francisco X Real, and Núria Malats. Journal of National Cancer Institute (2012). doi: 10.1093/jnci/djs444

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Nuria Noriega
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Centro Nacional de Investigaciones Oncologicas (CNIO)