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Alterations in vitamin D receptor gene increase prostate, breast cancer risk

Subtle differences in the receptor for vitamin D reverse the anti-cancer action of the sunshine vitamin, increasing the risk of breast cancer in Caucasian women and prostate cancer in African-American men, according to two new studies.

The results, in journals published by the American Association for Cancer Research, underscore how naturally-occurring variants of the same gene, called polymorphisms, can have implications for cancer initiation and progression.

For example, in the breast cancer study, British scientists at St. George's Hospital Medical School in London found that Caucasian women who carried specific versions of the vitamin D receptor gene, or VDR, not only experienced increased risk for this cancer but may also be more prone to developing metastases.

"Differences in the gene sequence for the vitamin D receptor are associated with breast cancer risk and may also be linked to disease progression" said Kay Colston, Ph.D., the senior author of the study, published in the August 15 issue of Clinical Cancer Research. Colston is a Reader in the Department of Cellular and Molecular Medicine at St. George's Hospital Medical School.

Among three known variable regions of the VDR gene considered by the research team, the bb and LL variants increased breast cancer risk by almost twofold. The F variant of the gene had no significant effect on breast cancer risk by itself, however when coupled with the LL genotype the risk of breast cancer was increased by a higher factor than the bb or LL genotypes alone. In addition, there was a higher proportion of women with this 'at risk' genotype in a sub-group of patients who developed metastatic disease.

A second study, conducted independently, linked a similar change in the vitamin D receptor (VDR) with amplified risk of prostate cancer for African American men. That study appeared in the August issue of Cancer Epidemiology, Biomarkers & Prevention, a sister publication to Clinic
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Contact: Russell Vanderboom, PhD
vanderboom@aacr.org
215-440-9300
American Association for Cancer Research
6-Aug-2004


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