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CHRNA3 genetic polymorphism and the risk of lung cancer in the Chinese Han smoking population

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Tumor Biology

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide that result from the combined effected of smoking exposure and genetic susceptibility. CHRNA3, a nicotinic acetylcholine receptor gene, was associated with lung cancer risk. The aim of this study was to identify whether CHRNA3 polymorphisms increase lung cancer risk directly or indirectly through smoking behavior in the Chinese Han individuals. We conducted a case–control study including 228 individuals with lung cancer and 301 healthy individuals. Seventeen known SNPs within CHRNA3 were selected for genotyping. Odds ratios (OR) and 95 % confidence interval (CI) were calculated by unconditional logistic regression with adjustment for gender and age. Two SNPs (rs8042059 and rs7177514) showed a 1.54-fold (p = 0.036; 95 % CI = 1.03–2.32) and 1.52-fold (p = 0.043; 95 % CI = 1.01–2.27) increased risk for lung cancer in smokers, respectively. Rs8042059 also showed a significant association for variant genotypes (CA/AA) compared with the wild-type genotype (CC), with an OR = 1.84 (p = 0.042; 95 % CI, 1.02–3.33) in the dominant model. In addition, the haplotype analysis found that the haplotypes “TCAC” and “CTGT,” composed of rs938682, rs12914385, rs11637630, and rs2869546, were associated with a 1.79-fold and 501-fold increased lung cancer risk, respectively. However, the polymorphisms of all SNPs were not significantly different between controls and cases among general or nonsmokers population. Rs8042059 and rs7177514 may increase lung cancer risk indirectly through smoking behavior in the Chinese Han population.

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Acknowledgments

This work is supported by the National 863 High-Technology Research and Development Program (No. 2012AA02A519) and National Science and Technology Major Project (No. 2012ZX09506001-007). We are grateful to all patients and individuals who participated in the study. We would also like to thank clinicians and other hospital staff who helped us to collect blood samples and data.

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    Authors and Affiliations

    1. School of Life Sciences, Northwest University, Xi’an, 710069, Shaanxi, China

      Wenjing Zhou, Huijuan Wang, Xiaojie Xun, Tianbo Jin & Chao Chen

    2. National Engineering Research Center for Miniaturized Detection Systems, Xi’an, 710069, China

      Tingting Geng, Huijuan Wang, Tian Feng, Hui Zou, Tianbo Jin & Chao Chen

    3. Key Laboratory of High Altitude Environment and Genes Related to Diseases of Tibet Autonomous Region, School of Medicine, Tibet University for Nationalities, Xianyang, 712082, China

      Longli Kang & Tianbo Jin

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    1. Wenjing Zhou
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    Correspondence to Tianbo Jin or Chao Chen.

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    Wenjing Zhou and Tingting Geng contributed equally to this work.

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    Zhou, W., Geng, T., Wang, H. et al. CHRNA3 genetic polymorphism and the risk of lung cancer in the Chinese Han smoking population. Tumor Biol. 36, 4987–4992 (2015). https://doi.org/10.1007/s13277-015-3149-0

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