Genetic region linked to a 5 times higher lung cancer risk

The researchers found a more than five times higher risk of lung cancer for people who have both a family history of the disease and these genetic variations. The risk was not affected by whether the study participants smoked or didn't smoke.

Published in the Sept. 13 issue of the Journal of the National Cancer Institute, this study is the fourth since April 2008 to implicate this genetic region in the development of lung cancer, and it strengthens the possibility that testing for variations in this region could become a valuable way to warn individuals of their higher risk.

"Many smokers don't get lung cancer, which suggests there is a genetic difference in smokers who do get the disease," says senior author Ming You, M.D., Ph.D., a researcher in cancer chemoprevention at the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital. "We also know that some families have a high incidence of lung cancer. If we can identify the genetic factors linked to lung cancer in such people before they get the disease, we can take steps to help prevent it. This genetic region might be part of the answer."

Lung cancer, the leading cancer killer in the United States, will likely cause 162,000 deaths in 2008 in men and women combined, according to projections. The National Cancer Institute indicates that cigarette smoking is linked to 87 percent of these deaths.

Among research groups studying lung cancer susceptibility, many other genetic markers of increased risk have been identified, but the area identified in this study on chromosome 15 is the only genetic region that is consistent across many studies, You says.

The three other recent studies that identified these specific genetic variations focused on sporadic lung cancer, but the current study established a strong risk factor in this chromosomal region for the kind of lung cancer that is inherited. Sporadic lung cancer occurs in individuals without a family history of lung cancer, while familial lung cancer, as defined for this study, is lung cancer that occurs in three or more direct blood relatives.

The three recent studies on sporadic lung cancer cited an approximately 30 percent greater risk for individuals with specific genetic variations in this region of chromosome 15, a much lower risk than found in the current study, You notes.

One of these studies indicated that smoking increases the risk when people have the genetic variations on chromosome 15, but two of the studies indicated that smoking adds no increased risk in such people. The increase in risk identified in the current study also was not dependent on whether a person smoked.

"If these genetic variations are associated with a five-fold increased risk, regardless of whether you smoke, that's very important information," says You, professor of surgery at the School of Medicine. "It would suggest that specific genes in this region and smoking are independent risk factors for lung cancer, and together they might cause an even greater increase in lung cancer risk."

The researchers looked at 194 people with familial lung cancer and compared their genetic profiles to 219 people over age 60 with no history of lung cancer. To make their study population as uniform as possible, only Caucasian subjects were included. DNA samples from blood or cheek swabs from each participant were screened for more than 300,000 known human genetic variations, or SNPs (pronounced "snips," these are points on chromosomes where people's DNA commonly differs by just one unit, or nucleotide).

The research group found several genetic variants, or SNPs, with a strong association to familial lung cancer on chromosomes 1, 3, 6, 9, 12 and 20, but a cluster of SNPs on the long arm of chromosome 15 had the strongest link to the disease. These genetic variants were found much more often in the study subjects with lung cancer. The statistical analysis of the data suggests that people with a family history of lung cancer and the variants on both copies of chromosome 15 have a 5.7- to 7.2-fold higher risk for developing lung cancer compared to the control group.

The chromosomal region that contains the high-risk-associated variations is the site of several known genes, including three that code for proteins implicated in nicotine addiction. That connection ties the genes to lung cancer associated with smoking, but some evidence also exists that the genes are directly involved in lung cancer development.

"These genes play roles in cellular proliferation and cell death," You says. "And they are active in lung cancer tumors. More research will be needed to fully delineate the part they play in lung cancer and whether they will be good targets for cancer therapies in the future."

Source: Washington University School of Medicine

Mechanisms of cardiovascular disease and cancer give clues to new therapies
Cardiovascular conditions leading to heart attacks and strokes are treated quite separately from common cancers of the prostate, breast or lung, but now turn out to involve some of the same critical mechanisms at the molecular level. This in turn provides clues to more effective therapies for both cancer and cardiovascular diseases, but requires researchers in these distinct fields to come together. The seeds were sown for closer cooperation between these two groups at a recent workshop organised by the European Science Foundation (ESF), which also highlighted the striking progress already made in understanding key common mechanisms underlying both disease categories.
Why only some former smokers develop lung cancer
Canadian researchers are trying to answer why some smokers develop lung cancer while others remain disease free, despite similar lifestyle changes.
Repairing DNA damage: Researchers discover critical process in cancer treatment
(PhysOrg.com) -- From the sun's UVA rays to tobacco smoke, our environment is chock-full of DNA-damaging agents that can lead to cancer. Thanks to our body's DNA repair mechanisms, however, the effects of many carcinogens can be reversed thereby preventing the formation of tumours.
Cancer patient genome sequenced for the first time
For the first time, scientists have decoded the complete DNA of a cancer patient and traced her disease - acute myelogenous leukemia - to its genetic roots. A large research team at the Genome Sequencing Center and the Siteman Cancer Center at Washington University School of Medicine in St. Louis sequenced the genome of the patient - a woman in her 50s who ultimately died of her disease - and the genome of her leukemia cells, to identify genetic changes unique to her cancer.
Researchers describe how chronic inflammation can lead to stomach cancer
A multi-center research team, led by Columbia University Medical Center, has uncovered a major contributor to the cause of stomach cancer – the second leading cause of cancer-related mortality in the world. The team described for the first time, that elevated levels of a single proinflammatory cytokine, an immune system protein called interleukin-1 beta (IL-1β), can start the progression towards stomach cancer. These results are published in the Nov. 4, 2008 issue of Cancer Cell. The researchers hope to use this finding to develop ways to block this process, thereby preventing cancer from developing.
Substance tackles skin cancer from two sides
By playing it safe and using a two-pronged attack, a novel designer molecule fights malignant melanoma. It was created and tested by an international team of researchers led by the University of Bonn. On the one hand, the substance is similar to components of viruses and in this way alerts the immune system. The body's own defences are also strengthened against cancer cells in this process. At the same time, the novel molecule also puts pressure on the tumour in a different way. It switches off a specific gene in the malignant cells, thus driving them to suicide. With mice suffering from cancer, the researchers have thus been able to fight metastases in the lung. In Nature Medicine's November issue they report about this promising strategy.
Scientists find new genes linked to lung cancer
Working as part of a multi-institutional collaboration, scientists at Washington University School of Medicine in St. Louis have assembled the most complete catalog to date of the genetic changes underlying the most common form of lung cancer. The research, published Oct. 23 in Nature, helps lay the foundation for more personalized diagnosis and treatment of a disease that is the leading cause of U.S. cancer deaths.
Anti-cancer drug prevents, reverses cardiovascular damage in mouse model of premature aging disorder
An experimental anti-cancer drug can prevent -- and even reverse -- potentially fatal cardiovascular damage in a mouse model of progeria, a rare genetic disorder that causes the most dramatic form of human premature aging, National Institutes of Health (NIH) researchers reported today.

Genetic region linked to a 5 times higher lung cancer risk

Related stories:

News discussion: