Study finds ‘smoking gun’ for oesophageal cancer

Queensland researchers have determined that sudden “chromosomal catastrophes” may trigger a third of oesophageal tumours, the fastest rising cancer in Australia.

The finding opens the way for further research into what triggers the catastrophic events, and whether patients at risk could take measures that may prevent tumours from developing.

The study involved scientists from QIMR Berghofer Medical Research Institute, The University of Queensland (UQ) School of Medicine and UQ’s Institute for Molecular Bioscience (IMB).

Dr Nic Waddell, who co-led the study, said the research was based on genome-wide sequencing of 22 patients with oesophageal adenocarcinoma (OAC) from three Brisbane hospitals.

“In 32% of patients there had been a catastrophic event that damaged the DNA which resulted in highly mutated and rearranged genomes, and we confirmed this finding in another 101 patients,” Dr Waddell said.

“In all patients there was evidence of genetic scarring or ‘footprints’ of damage to the DNA in the tumour cells.

“These findings have given us an important clue as to how these tumours might have eventuated.”

UQ School of Medicine’s Dr Andrew Barbour said OAC had one of the poorest outlooks of all solid tumours, with only 14 per cent of patients surviving five years.

“Removing the tumour is their best hope, but fewer than 50% of patients are diagnosed early enough for surgery,” Dr Barbour said.

He said the most significant risk factor for OAC was the pre-malignant lesion known as Barrett’s oesophagus.

“Patients with Barrett’s are routinely monitored for development of malignant tumours but reflux, smoking and obesity are other risk factors, and men account for eight in every nine OAC cases,” Dr Barbour said.

“The number of patients diagnosed with oesophageal cancer has doubled in the past 20 years and is expected to double again in the next two decades,” Dr Barbour said.

The study was funded by the NHMRC and follows a previous grant bringing together Australia’s major OAC scientists in a Centre of Research Excellence at QIMR Berghofer, where Dr Waddell is now based.

Director of QIMR Berghofer, Professor Frank Gannon, said he was thrilled to have a cancer genomics researcher of Dr Waddell’s calibre at the Institute as its bioinformatics capabilities expand.

The paper has been published by the scientific journal Nature Communications – http://www.nature.com/ncomms/2014/141029/ncomms6224/full/ncomms6224.html