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Cancer Research
March 9, 2010
Genetic Variant Greatly Increases Lung Cancer Risk for Light, Non-Smokers
March 2010
![Lit, smoking cigarette with child and two adults in silhoutte in front of lung image](https://webarchive.library.unt.edu/web/20120915124727im_/http://www.genome.gov/images/feature_images/smoke.jpg)
"Smoking is a poison for everybody," said co-author Joan Bailey-Wilson, Ph.D., a National Human Genome Research Institute (NHGRI) statistical geneticist and co-chief of NHGRI's Inherited Disease Research Branch. "For these folks, just a small amount of smoking puts them at high risk for lung cancer."
Each year, more than 1 million people worldwide die from lung cancer, including more than 150,000 in the United States. Smoking is by far the greatest risk factor for lung cancer and is associated with more than 75 percent of lung cancer deaths. The authors of the study point out the added importance of smoking prevention and early cancer detection procedures for individuals with a family history of lung cancer.
The analysis is part of a larger research initiative known as the Genetic Epidemiology of Lung Cancer Consortium (GELCC), a family study of lung cancer that has been ongoing for more than 10 years. The NHGRI and the National Cancer Institute (NCI) are among 12 participating research institutions and universities across the country engaged in the research.
The researchers followed up on clues from the study of 93 families who have had at least two incidences of lung cancer among relatives. Among those 1,500 individuals, nearly 500 were affected with lung cancer. In a 2004 study conducted by GELCC, the researchers identified a large region on human chromosome 6 that conferred a greater lung cancer risk in a subset of families with many affected individuals. In April 2009, the group identified a gene, RGS17, that is located in this region on chromosome 6, and that is associated with an increased susceptibility to lung cancer in family members with a history of the disease. Work is ongoing to determine if variants in the RGS17 gene account for increased lung cancer risk in the GELCC families that are linked to chromosome 6q.
The goal of the present study was to further characterize this previously noted signature of genetic susceptibility on chromosome 6q. This signature for lung cancer susceptibility was within a longer stretch of DNA than the RGS17 gene itself — a portion of chromosome 6q called a haplotype, containing multiple genes that tend to be inherited together.
To organize their data, the researchers divided smoking exposures into four categories: those whose smoking habit could be characterized as never, light, moderate or heavy.
For family members without the genetic lung cancer risk haplotype, the risk of developing the disease tracked closely with the level of smoking. As would be expected, heavy smokers take on a significantly greater risk of developing lung cancer than moderate smokers, who are at a significantly greater risk than light smokers.
But in family members with the genetic risk haplotype, even light smoking resulted in a greatly increased risk for developing lung cancer, "about 3-fold higher than in light smokers with unknown carrier status or non-carrier status," said Dr. Bailey-Wilson. This result stands out further because the risk of developing lung cancer in light smokers who carried the risk haplotype was very similar to the risk in moderate and heavy smokers who carry the susceptibility variant. However, in smokers, the risk of lung cancer was higher in carriers of the risk haplotype than in non-carriers for all levels of exposure. This suggests that any degree of smoking exposure confers high risk of lung cancer in family members with the risk haplotype.
"The findings are really intriguing and are consistent with everything else we have seen in past studies looking for major risk alleles for lung cancer," said Dr. Bailey-Wilson, explaining that the work is an ongoing effort. "More studies will need to be done to further define the risks and to explain the linkage signal in this region. If we determine exactly which gene is involved and how it works to increase cancer risk, it may help us target people who have extremely high risk from second-hand smoke and it may help us understand how lung carcinogenesis occurs. This might allow for better treatments and for targeted smoking cessation efforts."
Currently, there is no publically available genetic screening for the genetic variant on 6q responsible for this lung cancer susceptibility effect. Regarding advice to the public, Dr. Bailey-Wilson notes, "Anyone who smokes has a high risk of lung cancer, as well as increased risk for other diseases. Our best advice is to not smoke and to avoid exposure to passive tobacco smoke."
For more information about lung cancer, go to Lung Cancer [cancer.gov].
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Last Reviewed: May 15, 2012
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wendy8091 (October 7, 2010, 20:46)
why is this an insult? its only here to help those of us who are pre-disposed to lung cancer from whatever the cause may be. if your insulted then stop looking this up-just maybe your worried more than insulted????if i carry the gene i certainly want to know it-my mom carried it and died in 2005 from small cell lung cancer,she was 76 when she passed away and hadn't smoked in over 50 years-sure would have been nice to know she carried the genetic link before she got cancer, then just maybe we could have saved her....i got the letter yesterday telling me she carried the genetic link-now im wondering if i too have it? ive never smoked because of asthma-now severe asthma, or is it? at any rate i would want to know if i carried this link-smoker or not. grow up people grow up. stop being babies-ALL THIS IS SAYING IF YOU SMOKE AND CARRY THIS LINK YOUR CHANCES OF CANCER ARE GREATLY MAGNIFIED, OVER PEOPLE WHO DONT SMOKE. if you dont care whether you carry the link, keep smoking, if you do, get help to stop smoking. smoking is like any other addiction-its just that an addiction-an illness-so like i said if you care enough to research it-maybe you should stop smoking...if you choose not to stop-have respect for those of us who dont smoke, and are carriers of the link and DONT EXPOSE US TO SOMETHING WE DONT WISH TO BE AROUND. i dont want to die of lung cancer that could have been prevented-because i was exposed to 2nd hand smoke that i had no control over. btw my mom smoked outside and DID NOT EXPOSE ME because even back in the 50's she knew smoking wasnt good for your health and 2nd was as bad... -
Anonymous (July 13, 2010, 22:16)
Millions of people probably carry this gene. -
Baxter (March 22, 2010, 16:49)
You would feel less insulted if you didn't smoke. Its best to know the dangers of some thing as simple as smoking and to know if your putting people around you in danger. -
Abner (March 17, 2010, 19:04)
Tony, what is so insulting about this article? -
Tony Bell (March 17, 2010, 11:39)
I smoke and you are insulting me with this article and i think others would agree -
Robert (March 16, 2010, 12:53)
Scary -
Health Company (March 11, 2010, 04:11)
We all know Lung Cancer kills, but still many of us cant quit smoking -
Phyllis (March 9, 2010, 15:20)
Nice graphic!
I would like to know how to get tested for this gene due to an identical twin sister and another sibling with lung cancer.