Genetic variant contributes to higher risk of lung cancer, increases tendency to smoke more

Mar 11 2011

Norwegian researchers have discovered genes that increase not only one's risk of lung cancer, but perhaps one's urge to smoke as well. Now these researchers are working on developing a blood test for lung cancer.

"Smoking is by far the largest risk factor for developing lung cancer," says Professor Frank Skorpen of the Department of Laboratory Medicine, Children's and Women's Health at the Norwegian University of Science and Technology (NTNU) in Trondheim. Professor Skorpen is among the researchers in a project studying genetic factors and treatments for lung cancer. The project receives funding under the National Programme for Research in Functional Genomics in Norway (FUGE), one of the Research Council's seven Large-scale Programmes. Genetic factor doubles the risk

The risk of contracting lung cancer is relatively small for non-smokers. But the genetic factor for lung cancer found by the NTNU researchers nearly doubles that predisposition.

"This is a common genetic variant," explains the professor. "Roughly 10 per cent of the population has inherited this variant on both alleles, from mother and father, so there are many people with an increased risk of developing lung cancer."
The danger does not stop there, however: the NTNU research indicates that this allele also correlates with a tendency to smoke more than others, raising the risk of developing lung cancer even higher.

Follow-up to international project

This gene, located on chromosome 15, codes for nicotinic acetylcholine receptors in the body's cells. It is not yet understood exactly how these receptors contribute to a higher risk of lung cancer and tendency to smoke more.

Each year some 2 000 Norwegians die of lung cancer, the world's most common cancer type.

The gene was originally found in a major international project in which the NTNU group participated. The project involved scanning the entire human genome for genetic factors that increase predisposition to lung cancer.

The NTNU researchers continued working on the genetic variant found to most increase the likelihood of developing lung cancer.

Smokers and non-smokers

Now they are analysing samples from the entire population of Norway's Nord-Trøndelag County, taken as part of the HUNT health study and encompassing over 57 000 persons.

"This is a large, homogenous population," says Professor Skorpen, "one that includes both smokers, former smokers and non-smokers."

The researchers aim to discover whether people who carry the genetic risk markers for lung cancer tend to smoke more, and how large a difference there may be among smokers, former smokers, and those who have never smoked.

Blood test for lung cancer

The chromosome-15 gene is associated with a certain type of lung cancer, adenocarcinoma. The NTNU researchers are examining the possibility of developing a blood test that can detect this and other types of lung cancer.

Compared to male smokers, women who smoke are more disposed to lung cancer. Since coughing is the main symptom, the disease is particularly difficult to discover in smokers.

"We're examining whether lung cancer may affect gene expression in white blood cells," continues Professor Skorpen. "A tumour secretes various signalling compounds, which are transported in the blood. Perhaps some of these transmitters alter the gene expression in the white blood cells."

If the researchers can find a gene expression signature in white blood cells that is specific to lung cancer, they may detect a patient's lung cancer at an earlier stage.
This would parallel other cancers, such as breast cancer, in which the expression of multiple genes in blood cells is altered. Identifying these changes can provide an early indication of the disease.

Samples from Biobank Norway

To find out whether gene expression signatures can be identified in blood, the researchers have been using blood samples stored at the Central Norway lung cancer biobank from lung cancer patients, and from healthy control samples from Nord-Trøndelag's HUNT biobank.

The researchers isolated total RNA from the blood of 100 lung cancer patients and compared it to samples from 100 cancer-free individuals. The results are still being analysed.

"If we are able to find blood markers that indicate lung cancer, we will need to repeat the study on larger groups of patients and healthy control subjects," explains Professor Skorpen. "These analyses are painstaking and complicated, and it is necessary to replicate the findings with a larger material sample. This will eventually be possible as the lung cancer biobank expands."