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I. Cheng
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-072 - Gene-Smoking Interactions in Lung Cancer Etiology (ID 2653)
09:30 - 17:00 | Author(s): I. Cheng
- Abstract
Background:
Even among heavy smokers, the lifetime risk for developing lung cancer is between 15 and 20% which raises a question about whether there are protective factors that mitigate risk from toxic exposures in tobacco smoke. Previously we have shown significant gene-environment interaction effects between smoking and genetic loci on chromosome 15q25.1 near the nicotinic acetylcholine receptor locus contrasting minimal increases in risk for never smokers from SNPs in this region versus substantial impact on risk for smokers. Studies contrasting risk in heavy versus light smokers have not been conducted and little is known about protective factors that may reduce risk for some smokers.
Methods:
In order to identify genetic factors that might reduce lung cancer risk, we performed a genome-wide case only analysis of lung cancer risk, comparing heavy to light smokers. This approach to analysis is powerful for identifying gene-environment interactions provided there is no correlation between the genetic factor and the environment exposure. We performed a genome-wide association of heavy smokers who had a 30 packyear or more background of smoking versus 1824 lung cancer cases with less than 30 packyears of smoking exposure using data derived from studies conducted by 7 sites within the Transdisciplinary Research in Cancer of the Lung (TRICL) consortium. To improve our ability to identify genetic variants, we used imputation based on the March 2012 release of the 1000 Genomes to impute and analyze data from more than 9 million genetic variants.
Results:
This analysis identified one region showing many highly significant associations with the most significant being rs62180069 (p=5x10-8, OR = 0.76). This SNP lies between the SCHLAP1 gene encoding the SWI/SNF complex antagonist with prostate cancer 1, non protein coding, gene and the gene UBE2E3 on chromosome 2. At this locus there was no gene-smoking correlation in the controls and no evidence for heterogeneity in strength of association among the 7 contributing studies.
Conclusion:
UBE2E3 is the ubiquitin conjugating enzyme E3. This gene is overexpressed in a substantial number of lung cancers. Further studies to characterize the impact of this variant on lung cancer risk according to further variation in smoking behavior and also impacts on function are warranted.
