Genetic mutation linked to lung cancer

The aggressiveness of a lung cancer tumour and the risk of it spreading have been linked to a gene mutation, The Daily Telegraph reported. The discovery of this gene “could lead to the development of a test that would allow doctors to treat the disease more effectively”, and patients “could be given varying doses of chemotherapy drugs depending on which form of the gene they had” the newspaper said on August 6 2007.

The story was based on two pieces of combined research: an animal study carried out in mice and a description of the genetic characteristics of 144 human lung cancer tumours.

As with all animal studies, it is impossible to extrapolate the findings directly to humans. The second part of this study found that only 34% of human lung tumours had the mutations in the gene that the researchers were investigating.

The news report may have overstated the link between this mutation and lung tumours. There is some way to go before the implications of this link for humans will be understood.

Where did the story come from?

Hongbin Ji and colleagues at the Harvard Medical School and other medical institutions across the US conducted this research and it was supported by various institutions including the National Institutes for Health (NIH), the Sidney Kimmel Foundation for Cancer Research, the American Foundation of Aging, and the Harvard Stem Cell Institute. It was published in the peer-reviewed medical journal, Nature .

What kind of scientific study was this?

In the first part of the study, mice with particular genetic mutations (including a mutation in a gene called LKB1) were given a virus that causes lung tumours. The researchers then investigated the effects of the mutations and the interactions between the different genetic mutations and the characteristics of the lung tumours that developed in the mice.

In the second part of the study, the researchers looked at DNA from 144 frozen samples of human lung cancer tumours and looked for the presence of four mutations, including the mutation at LKB1.

What were the results of the study?

In the first part of the study, the mice with a mutation in the LKB1 gene were seen to have more aggressive tumours than the mice with mutations in other genes. Mice with the LKB1 mutation also developed a greater range of tumours than those with the other mutations.

In the second part of the study, the researchers found an LKB1 mutation in 34% of the human lung adenocarcinomas and in 19% of the human squamous cell carcinomas. Both adenocarcinomas and squamous cell carcinomas are forms of lung cancer in humans.

What interpretations did the researchers draw from these results?

The authors concluded that mutation in the LKB1 gene affects the ability of a cell to suppress the development of a tumour. This gene seems to be involved in the initiation, growth and spread of lung tumours.

What does the NHS Knowledge Service make of this study?

This study appears to have been well-conducted. There are a few points to bear in mind when interpreting the results:

• Lung cancer is a complex disease in humans and the risk of developing it is affected by several factors, including environmental factors such as smoking. Variations in a single gene are not responsible for all cases of lung cancer.
• It is impossible to extrapolate findings from animal studies to humans. In this case, the mutation in the gene was found in only 34% of the human tumours that were analysed. This highlights the importance of other factors in causing the tumours.
• Knowing that there is an association between the LKB1 mutation and some lung cancers does not mean that researchers would know how to prevent cancer in people with this mutation. The combination of this and the factors mentioned above means that the testing of people for this variant is a long way in the future. 
• More research is needed before the implications of this discovery for humans can be understood.