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 Clinical Cancer Research.

Intriguingly, the F variant that increases the chance of developing breast cancer when associated with other VDR variants also contributes to increased risk and aggressiveness of prostate cancer in African-American men, according to the Cancer Epidemiology, Biomarkers & Prevention article.

This study reported that men with two copies of the F variant almost doubled the risk for prostate cancer developing in African-Americans, but not Caucasians. Furthermore, the same men had twice the risk for developing high grade advanced prostate cancer, according to the research.

"More African-American prostate cancer patients carried the homozygous FF variant of the vitamin D receptor than African American men who did not have prostate cancer," said Alice S. Whittemore, Ph.D., the senior author of the paper. Whittemore, who conducts cancer research in the department of Health Research and Policy, the Stanford University School of Medicine, led a multi-institutional team of cancer scientists from Stanford University, the University of Southern California, the University of Hawaii, the British Columbia Cancer Agency and the Northern California Cancer Center.

Neither the b nor L gene variants that altered risk in Caucasian women in the British study contributed to elevated risk for prostate cancer among men.

Funding for the prostate cancer studies came from NIH grant CA67044. The UK breast cancer study was funded by Breast Cancer Campaign and the World Cancer Research Fund.

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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