A team of cancer researchers at John Hopkins University have identified a new gene which could help explain the dietary links to prostate cancer. The gene could have a vital role in the breakdown of fatty acids found in dairy products and beef, foods often associated with high risk of the cancer.
Cells taken from prostate cancers show a nine-fold increase in expression by a gene called AMACR (x-methylacyl-CoA racemase), a team of Hopkins investigators report in the 15 April issue of Cancer Research.
"This gene appears to play an important role in breakdown of branched chain fatty acid molecules such as those found in dairy products and beef," said Dr William B. Isaacs, professor of urology and oncology at the Brady Urological Institute and Kimmel Cancer Center at Johns Hopkins, and senior author of the study.
The fatty acid molecules metabolised by an enzyme made by the AMACR gene are low in chicken and most fish. Several studies have shown diets high in red meat to be associated with an increased risk of prostate cancer.
"What we've learned about AMACR could not only serve as an excellent early marker for prostate cancer but also could identify new dietary or chemical means of preventing the disease," said Angelo M. De Marzo, co-author of the study and assistant professor of pathology, oncology, and urology at Johns Hopkins.
However the Hopkins scientists insisted that the link, if any, between increased expression of AMACR and eating beef and dairy foods was unclear and was the focus of ongoing research.
In the study, the researchers used a comprehensive "gene chip" approach to simultaneously analyse the expression of more than 6500 genes and found that the AMACR gene was overexpressed in prostate cancers. They confirmed this by examining 168 prostate cancer tumours using a tissue microarray that rapidly evaluates gene expression. Using automated computer technology, they displayed the tissue microarrays to speed up the identification of relationships among genes and changes in normal and cancer cells.
More than 95 per cent of the tumours analysed showed overexpression of the AMACR gene, making it one of the most consistent biological markers known for prostate cancer. Similar overexpression patterns were found in precancerous lesions, called high grade prostatic intraepithelial neoplasia.
"Since AMACR enzymatic activity is not found in most normal tissues, it could be an excellent candidate for the development of molecular probes for non-invasive detection of prostate cancer and as a potential drug target," said Dr June Luo, lead author of the study.
The AMACR gene was revealed in the last two years as a potential prostate cancer marker by researchers at the Corixa Corporation and then at the University of Massachusetts Medical School in Worcester. Since then, it has been independently identified by the Hopkins group and a research team at the University of Michigan.
The search for better prostate cancer diagnostic tools is driven in part by uncertain outcomes of needle biopsies. "As many as 15 per cent of needle biopsies are inconclusive and must be repeated," De Marzo said. "Markers that can enhance diagnostic accuracy the first time are urgently needed," he added.