Chromosome 15q25 (CHRNA3-CHRNB4) Variation Indirectly Impacts Lung Cancer Risk in Chinese Males

• Published in: PloS one 2016-03, Vol.11 (3), p.e0149946
• Main Authors: Zhang, Yalei, Jiang, Mei, Li, Qin, Liang, Wenhua, He, Qihua, Chen, Weiqing, He, Jianxing
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Alleles; Asian Continental Ancestry Group - genetics; Biology and Life Sciences; Cancer; Carcinogens; Case management; Case-Control Studies; China; Chromosome 15; Chromosomes; Chromosomes, Human, Pair 15 - genetics; Cigarette smoking; Cigarettes; Demographics; Deoxyribonucleic acid; Disease; DNA; Epidemiology; Genetic aspects; Genetic Predisposition to Disease; Genetic Variation; Genomes; Genotypes; Health care; Health risk assessment; Health risks; Hospitals; Humans; Laboratories; Lung cancer; Lung diseases; Lung Neoplasms - ethnology; Lung Neoplasms - genetics; Male; Males; Medical statistics; Medicine and Health Sciences; Metabolites; Middle Aged; Mutation; Nerve Tissue Proteins - genetics; Nicotine; Physiological aspects; Polymorphism, Single Nucleotide; Population; Public health; Receptors, Nicotinic - genetics; Research and Analysis Methods; Respiratory diseases; Risk; Risk Factors; Risk taking; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Smoking; Social Sciences; Studies; Surgery; Thoracic surgery; Tobacco; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0149946

Recently, genome-wide association studies (GWAS) in Caucasian populations have identified an association between single nucleotide polymorphisms (SNPs) in the CHRNA5-A3-B4 nicotinic acetylcholine receptor subunit gene cluster on chromosome 15q25, lung cancer risk and smoking behaviors. However, these SNPs are rare in Asians, and there is currently no consensus on whether SNPs in CHRNA5-A3-B4 have a direct or indirect carcinogenic effect through smoking behaviors on lung cancer risk. Though some studies confirmed rs6495308 polymorphisms to be associated with smoking behaviors and lung cancer, no research was conducted in China. Using a case-control study, we decided to investigate the associations between CHRNA3 rs6495308, CHRNB4 rs11072768, smoking behaviors and lung cancer risk, as well as explore whether the two SNPs have a direct or indirect carcinogenic effect on lung cancer. A total of 1025 males were interviewed using a structured questionnaire (204 male lung cancer patients and 821 healthy men) to acquire socio-demographic status and smoking behaviors. Venous blood samples were collected to measure rs6495308 and rs11072768 gene polymorphisms. All subjects were divided into 3 groups: non-smokers, light smokers (1-15 cigarettes per day) and heavy smokers (>15 cigarettes per day). Compared to wild genotype, rs6495308 and rs11072768 variant genotypes reported smoking more cigarettes per day and a higher pack-years of smoking (P