Colorectal cancer

Illustration: courtesy Centre for Immunology and Cancer Research (CICR)
Research team:
Professor Jeremy Jass (School of Medicine, Central Clinical Division), Associate Professor Barbara Leggett (School of Medicine, Central Clinical Division and Conjoint Gastroenterology Laboratory, Royal Brisbane Hospital (RBH) Research Foundation), Dr Joanne Young (School of Medicine, Royal Brisbane Hospital) and Kelli Biden (Conjoint Gastroenterology Laboratory, RBH Research Foundation)
Funding:
1998?2000 NHMRC ($148,500)
2001?2003 NHMRC ($360,000)
Email/Web link:
barbaraleggett@health.qld.gov.au
Faculty of Health Sciences
Discovery of an "unzipper" gene may lead to techniques for reversing colorectal cancer.

According to a series of upcoming research publications, colorectal cancer is one of the most common cancers in the western world, with one in 30 Australians eventually dying due to the disease.

Although previous studies had revealed some people might have a genetic disposition to colorectal cancer, the new research shows that an alternative cause of this cancer is a polyp with saw-tooth shaped glands.

Dr Joanne Young, Kelli Biden, Professor Jeremy Jass and Associate Professor Barbara Leggett recently reported their findings in the journal Proceedings of the National Academy of Science.

"In healthy individuals, the new gene (called HPP1) may act as an 'unzipper', allowing cells to break away from the gut lining as they become old and damaged. By jamming the unzipper mechanism, potentially dangerous cells are retained and this increases their chances of changing into cancer cells," Professor Jass said.

The HPP1 gene is jammed or silenced by a chemical alteration known as methylation. This chemical change to the unzipper gene is not a permanent mutation but a potentially reversible alteration. A compound able to reverse methylation in the laboratory is aza-deoxycytidine and there is growing interest in the use of this chemical in the treatment of malignancies such as leukaemia. HPP1 joins the growing number of cancer genes that are silenced by methylation.

"What we have found is exciting because the process of colorectal cancer growth may be reversible or preventable," Professor Jass said.

"The currently accepted belief is that colorectal cancer develops within a pre-existing benign polyp that has been present for many years, perhaps decades. However, extended studies have shown that removing the polyps has had little impact on the incidence of cancer.

"This indicates that a different mechanism may be possible for colorectal cancer. The new process we have found is much quicker and occurs in a different type of polyp, which was previously thought to be completely innocent.

"The presence of a new and more rapid cancer process means that the accepted slow evolutionary model of cancer growth has generated a false sense of security and false hope for cancer prevention. We need to address this new cancer-forming process to cure and prevent colorectal cancer."

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