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Member Research & Reports

Member Research & Reports

LSUHSC, Moffitt, and Tulane Identify the Role of Nicotine Dependence Biomarkers in Lung Adenocarcinoma

Researchers at the LSUHSC School of Public Health and the Stanley S. Scott Cancer Center, teamed with the H. Lee Moffitt Cancer Center and Tulane University to study the impact of nicotine dependence on the relationship between genetic variants in the region of CHRNA5/A3/B4 – three of the five known nicotinic receptor related genes – and lung adenocarcinoma (ADC) risk.

Tseng Photo

Smoking is the major risk factor for lung cancer, the leading cause of cancer deaths in the U.S. in 2014. The majority of lung cancer patients are diagnosed at advanced stages, and the five-year survival rate for these patients is less than 10 percent.  Effective early detection tools are still under development. There is an urgent need for identifying additional biomarkers to improve the accuracy of predicting lung cancer. Several variations in nicotinic receptor genes have been identified to be associated with both lung cancer risk and smoking, in genome-wide association studies (GWAS). However, the relationships among these three factors (genetic variants, nicotine dependence, and lung cancer) remain unclear.

The researchers applied mediation analysis to quantify the impact of nicotine dependence on the association between the nicotinic receptor genetic variants and lung adenocarcinoma risk. They evaluated 23 single nucleotide polymorphisms (SNPs) in the five nicotinic receptor related genes (CHRNB3, CHRNA6, and CHRNA5/A3/B4) previously reported to be associated with lung cancer risk and smoking behavior.  These were compared to 14 SNPs in the four ‘control’ genes (TERT, CLPTM1L, CYP1A1, and TP53), which were not reported in the smoking gene wide association studies (GWAS).

A total of 661 lung adenocarcinoma cases and 1,347 controls with a smoking history, obtained from the Environment and Genetics in Lung Cancer Etiology case-control study, were included in the study.  The objective was to characterize the mediation effects of nicotine dependence on the relationship between genetic variants in the five nicotinic receptor genes (CHRNA5/A3/B4, CHRNB3, and CHRNA6) and lung ADC risk among ever smokers.

The findings suggest that nicotine dependence plays an important role (account for 15 percent) between genetic variants in the CHRNA5/A3/B4 region and lung adenocarcinoma. This may provide valuable information for understanding the pathogenesis of lung adenocarcinoma, and for conducting smoking cessation interventions, which are based on more personalized risk estimates.

Role of Nicotine Dependence on the Relationship between Variants in the Nicotinic Receptor Genes and Risk of Lung Adenocarcinoma” was co-authored by Dr. Tung-Sung Tseng, assistant professor at LSUHSC, Dr. Jong Y. Park, researcher as Moffitt Cancer Center, Dr. Jovanny Zabaleta, assistant professor at LSUHSC, Dr. Sarah Moody-Thomas, professor at LSUHSC, Dr. Melinda S. Sothern, professor at LSUHSC, Dr. Ted Chen, professor at Tulane University, Dr. David E. Evans, researcher at Moffitt Cancer Center, and Dr. Hui-Yi Lin, researcher at Moffitt Cancer Center.