Reporter 455, 25 September 2000

Test offers early clue to cancer risk

A diagnostic approach developed at the University, bringing molecular biology into the clinic, offers new hope of identifying for timely treatment a group of patients at high risk of developing a life-threatening cancer.

About one in a hundred people have Barrett’s oesophagus, a condition in which the normal lining of the oesophagus (or gullet) is replaced by cells with a distinctive, column-like appearance under the microscope.

Danger signals: Professor Chris Wild and research fellow Dr Laura Hardie check biopsy samples for early signs of a predisposition to cancer of the oesophagus

These people are 40 times more likely than most to develop oesophageal cancer – which has doubled in incidence in the last decade.

Kamal Bani-Hani and colleagues at the School of Medicine discovered that biopsy specimens from patients with Barrett’s oesophagus (known as BE) show up an excess of a particular protein, cyclin D1, and this can signal who is likely to develop the cancer.

The protein has a part to play in regulating cell division, and overexpression is thought to be one of the genetic alterations associated with oesophageal cancer. Only a small fraction of patients with BE will develop the cancer – but diagnosis is normally made at an advanced stage, when the outlook is bleak. A method is needed to indicate which patients are at increased risk.

The authors worked with 307 patients with BE. At intervals, endoscopic examinations were made and biopsy specimens were taken from the region of BE. They were analysed by staining with a specific antibody for over-expression of the protein cyclin D1.

Twelve patients with BE developed cancer of the oesophagus and each was matched with up to six control patients with BE who did not develop cancer. Sixty-seven percent of those who developed cancer had shown up positive for cyclin D1 when they were first diagnosed with BE. By contrast, only 29 percent of the matched control patients had biopsies that were positive for cyclin D1. Patients whose biopsy specimens stained positive for the protein were six to seven times more likely to develop oesophageal cancer than the others.

Kamal Bani-Hani, who researched at Leeds under Professor Chris Wild of the Molecular Epidemiology Unit and Leeds General Infirmary surgeon Iain Martin, is now teaching in Jordan University of Science & Technology.

Prof Wild said his PhD student’s findings would have useful resource implications for health services as well as helping in the clinical tracking of individual cases.

"Costs and discomfort could be reduced by avoiding unnecessary tests on low-risk patients, while the survival rates of the higher-risk people should improve," he said.

More More information is available:
full version of the document
molecular epidemiology website

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