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

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

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