CHRNA3 and nicotine dependence: Although it has been reported that nicotine-mediated activation of CHRNA3 and CHRNA5 can influence lung cancer risk directly, it also has been suggested that the 15q25.1 lung cancer susceptibility locus influences lung cancer risk at least in part through an effect on smoking persistence [12] because the variants at 15q25.1 are also associated with smoking behavior and nicotine dependence [13].