Navigation Links
Genetic variations raise lung cancer risk for smokers and ex-smokers
Date:4/2/2008

HOUSTON - Two common inherited genetic variations are associated with increased risk of lung cancer for smokers and former smokers, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center reports April 2 in the online edition of Nature Genetics.

"This is the first study to identify a common genetic variant that influences the risk for developing lung cancer," said lead author Chris Amos, Ph.D., professor in M. D. Anderson's Department of Epidemiology. The variants are present in about half of the Caucasian population studied.

The paper is one of three published by Nature this week from three unique teams that have identified the same genetic locus as associated with increased lung cancer risk. The findings are a major step forward in identifying those at high risk for non-small cell lung cancer and for understanding how smoking and genetic factors interact to cause the disease.

"The major risk factor for developing lung cancer is cigarette smoking," Amos said. "What we do not understand is why some long-term smokers develop lung cancer and others don't. There are so many different cancer-causing compounds in tobacco smoke that it's hard to separate them and we don't fully understand the mechanisms that cause lung cancer."

While all smokers and former smokers are at higher risk for lung cancer, less than 20 percent of these "ever smokers" eventually develop the disease. "We need to get a better handle on how genetic factors increase risk and what molecular pathways are involved in development of lung cancer," Amos said.

The research team, comprising scientists from M. D. Anderson, Johns Hopkins University, and the Institute for Cancer Research and the University of Cambridge in the United Kingdom, pinpointed two spots of genetic variation on chromosome 15.

The two variants are single-nucleotide polymorphisms (SNPs, pronounced "snips"), places in the human genome that vary by a single DNA chemical building block or nucleotide. Individuals who have ever smoked and who have one or two copies of either of these SNPs have increased risks ranging from 28 percent to 81 percent of developing lung cancer, the researchers found.

The team's findings might also provide support for a growing body of evidence suggesting that nicotine, long known as the prime addictive compound in cigarettes, might also play a direct causative role in the development of lung cancer.

There are five genes in the area of chromosome 15 where the two risk-raising SNPs were identified, Amos explained. Of those, three are nicotine acetylcholine receptor genes that encode proteins that serve as docking sites to which nicotine can bind.

"Once bound, these receptors set in motion a cascade of signals. Nicotine is known to activate cell proliferation, new blood vessel development and growth factors while upregulating several signaling pathways. If these are indeed causal genes, that will be of great interest," Amos said.

Another potential causative gene in the area is one that encodes a component of the proteasome, which degrades other proteins. The function of the fifth gene has yet to be identified.

Further studies with additional SNPs in African-American populations who show different SNP patterns may help to define which of these five genes causes lung cancer. Collaborations with both M. D. Anderson's Lung SPORE and the Kleberg Center for Molecular Markers will evaluate whether these SNPs influence expression of any of these five genes in lung cancers and normal lung tissue, Amos said.

Lung cancer causes more deaths than any other cancer, killing more than 160,000 Americans annually and millions worldwide. Non-small cell lung cancer makes up 80 percent of all lung cancer cases.

Amos and senior co-author Margaret Spitz, M.D., chair of M. D. Anderson's Department of Epidemiology, conceived the study, which follows on evidence from epidemiological research indicating a two-fold increase in lung cancer risk for first-degree relatives of lung cancer patients.

To pinpoint genetic variations, the team conducted a series of genome-wide association studies, first genotyping 317,498 different SNPs among 1,154 former and current smokers who developed lung cancer and were seen at M. D. Anderson and 1,137 matched ever-smoker controls in Houston.

This first phase of the study narrowed the search to 10 SNPs, which were then genotyped in 711 additional cases and 632 controls from the same Houston population to identify the final two SNPs. A second replication phase was conducted among 2,013 ever-smoker lung cancer cases and 3,062 controls in the United Kingdom.

To minimize confounding from risk factors and to increase the study's ability to pinpoint genetic effects, controls were matched to lung cancer cases according to smoking behavior, age and sex. Former smokers were matched by years since they stopped smoking. The study was performed first in Caucasians to minimize the effect of ethnic genetic variation.

The team carefully analyzed its findings to exclude the possibility that the elevated risk from the two SNPs was attributable to their association with heavier smoking. "Our study shows a weak effect (of these two SNPs) on smoking behaviors and an extremely significant effect on lung cancer risk, whether or not adjustment for smoking behavior is made during the analysis," the authors conclude.

The genetic variations might help identify smokers at higher lung cancer risk who would be the best candidates for screening. And they may be useful to gauge the risk of other smoking-related cancers, such as esophageal, bladder, head and neck, and pancreatic cancer. A similar genome-wide study of African-American smokers is planned.

Research was funded principally by the National Cancer Institute of the National Institutes of Health. Lung cancer patients and controls for the Texas components of the study came from a long-term, 17-year study of the epidemiology of lung cancer at M. D. Anderson, which was funded by the National Cancer Institute and led by Spitz.

"We are very indebted to the patients who have participated in the study," Spitz said. "There is no immediate benefit to the patients themselves, but they willingly agree to participate in our research and their help has been invaluable. Being able to conduct this analysis should be useful to future generations who develop lung cancer."


'/>"/>

Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

Related medicine news :

1. Many Parents Share Genetic Test Findings With Kids
2. Genetic predisposition increases childhood asthma risk
3. New Alzheimers findings: High stress and genetic risk factor lead to increased memory decline
4. Test Spots Genetic Damage Done by Smoking
5. Scientists demonstate link between genetic variant and effectiveness of smoking cessation meds
6. Scientists highlight benefits of genetic research in sport, but warn of ethical concerns
7. Genetics Hold Promise, Challenges for Cancer Care
8. Researchers genetically engineer micro-organisms into tiny factories
9. Study Questions Genetic Screening for Treatable Diseases
10. Researchers provide genetic associations from a genome-wide scan for cardiovascular disease traits
11. Genetic variation affects smoking cessation treatment
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Genetic variations raise lung cancer risk for smokers and ex-smokers
(Date:10/13/2017)... RIDGE, N.J. (PRWEB) , ... October 13, 2017 , ... ... annual Holly Day Market. Featuring a collection of specialty vendors and unique items from ... of personalized and quality-focused health and wellness services offered by the VNA. The ...
(Date:10/13/2017)... ... 13, 2017 , ... Yisrayl Hawkins, Pastor and Overseer at The House of ... popular and least understood books in the Holy Scriptures, Revelation. The Book of Revelation ... scholars for centuries. Many have tossed it off as mere rubbish, but Yisrayl Hawkins ...
(Date:10/13/2017)... ... ... “The Journey: From the Mountains to the Mission Field”: the story of a missionary ... Journey: From the Mountains to the Mission Field” is the creation of published author, ... ages and currently teaches a class of ladies at her church, which she has ...
(Date:10/12/2017)... ... October 12, 2017 , ... CitiDent ... sleep apnea using cutting-edge Oventus O2Vent technology. As many as 18 million ... by frequent cessation in breathing. Oral appliances can offer significant relief to about ...
(Date:10/12/2017)... CITY, Fla. (PRWEB) , ... October 12, 2017 , ... ... cold therapy products, announced today the introduction of an innovative new design of the ... multipurpose pad so you get maximum comfort while controlling your pain while using cold ...
Breaking Medicine News(10 mins):
(Date:10/12/2017)... AVACEN Medical , Inc. (AVACEN) announced that ... New Product Innovation Award for Its fibromyalgia pain management ... medical device market research by Frost & Sullivan,s industry experts. ... pain relief product, the AVACEN 100, offers a safe and ... pain. ...
(Date:10/11/2017)... 2017  Caris Life Sciences ® , a leading ... of precision medicine, today announced that St. Jude Medical ... Alliance™ (POA) as its 17 th member. Through ... Crosson Cancer Institute will help develop standards of care ... profiling, making cancer treatment more precise and effective. ...
(Date:10/10/2017)... EXTON, Pa. , Oct. 10, 2017   ... leader in innovative solutions for injectable drug administration, today ... of West,s ID Adapter for improving the intradermal administration ... the Fourth Skin Vaccination Summit in May 2017 by ... Team Lead, Polio Department, World Health Organization (WHO), and ...
Breaking Medicine Technology: