Friday October 29 2010
It takes 11.7 years for the gene mutation to turn into a tumour
“Lethal pancreatic cancer grows for decades,” according to the BBC. The cancer may “lurk in the body for many years before patients fall ill”, it said.
The news is based on a study that has estimated the way pancreatic cancer progresses by examining tumours taken from seven patients killed by the disease. By examining the genetics of these tumours, scientists calculated that the first cancer-related mutations in pancreatic cells take place on average 18 years before the cancer is able to spread to other organs. It takes about 20 years before patients die from the disease.
This laboratory study has used genetic sequencing and a mathematical model to estimate the patterns of progression for pancreatic cancer, a disease that often goes undetected until it reaches an incurable stage. While its conclusions would need to be confirmed in further studies, they suggest that there could be a large window of opportunity to detect and treat the cancer before it spreads and becomes lethal. As things stand, only 2-3% of people with advanced pancreatic cancer are alive five years after their first diagnosis, and research in this area is of great importance.
Where did the story come from?
The study was carried out by researchers from the Johns Hopkins Medical Institutions, the Kimmel Cancer Centre in Baltimore, Harvard University and the University of Edinburgh. It was funded by the US National Institutes of Health and several charitable foundations and research centres. The study was published in the peer-reviewed journal Nature.
It was well reported by the BBC, which explained the methods used by the researchers and reported the opinions of independent experts.
What kind of research was this?
This was a laboratory study that used genetic analysis to look at cancer cells removed from seven patients who had died of end-stage pancreatic cancer. In particular, researchers studied the relationship between cancer mutations in the primary tumour (found in the pancreas) and cancer cells in secondary tumours found in other organs.
The authors point out that metastasis (the spread of cancer cells from the primary tumour to other organs) is the most common cause of death in cancer patients. This is particularly true of pancreatic cancer where, it is reported, most patients are diagnosed with metastatic disease and few are successfully treated. They say that it is unknown whether the “dismal” outlook for these patients compared to those with other cancers is due to late diagnosis or early spread of the disease.
What did the research involve?
The researchers performed rapid autopsies of seven individuals who had died of end-stage pancreatic cancer. All of these patients were confirmed as having secondary cancers in two or more organs other than the pancreas - most often in the liver, lung and peritoneum (lining of the abdominal cavity).
The researchers took tissue samples from the primary tumours in the pancreas and from secondary tumours in other parts of the body.
They sequenced the DNA in the genes of seven of these secondary tumours, to determine the “clonal relationship” between cells in the primary tumour and those in the secondary cancer deposits, i.e. whether there were any genetic differences between the cancers cells at different tumour sites. They then used a mathematical model to estimate the timing of the development of various stages of the cancer progression (its “genetic evolution”).
What were the basic results?
The researchers found that on average, each of the secondary tumours studied had 61 cancer-related mutations. On average, 64% of these had been present in the original primary tumour in the pancreas.
They also estimated that on average:
- it took 11.7 years for the original cancer-related gene mutation in the pancreas to progress into a primary cancer
- there was a further gap of 6.8 years between the development of the primary cancer and the development of cells with the ability to spread and form secondary deposits (metastases)
- there was a gap of 2.7 years between the appearance of these metastatic cancer cells and the patients dying
How did the researchers interpret the results?
The researchers say there is a “window of opportunity” of at least a decade for early detection and treatment during which the disease it is still curable. At present, most patients are not diagnosed until the last two years of the cancer process, when the condition is far harder to treat and the chances of survival are much lower. The challenge we now face is to detect these tumours at an earlier stage. Their findings, the researchers say, could have major implications for screening policies to prevent cancer deaths.
As external experts have pointed out, pancreatic cancer is the UK’s fifth biggest cause of cancer deaths. Survival rates have not improved in the past 40 years. This small study, involving tissue from seven patients with advanced pancreatic cancer, appears to suggest that the cancer slowly progresses from its early stages over a number of years and that there is a lengthy time lag between the first cell changes and the appearance of secondary tumours.
These findings will need to be replicated in larger studies. But, as the researchers say, they provide further understanding of the genetics of pancreatic cancer and may possibly indicate an opportunity for early detection and treatment of this disease, which proves fatal in the majority of cases.