title: Beta-2 adrenergic receptor gene (ADRB2) polymorphism and risk for lung adenocarcinoma: a case-control study in a Chinese population.
abstract: The incidence of lung adenocarcinoma (AC) has been increasing over recent decades. The tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most potent carcinogens and reproducibly induces a high incidence of lung AC in laboratory animals. In addition to its genotoxic effects, NNK has also epigenetic effects on lung cells by functioning as an agonist for beta adrenergic receptors and stimulating the signal pathways that lead to lung AC. Beta-2 adrenergic receptor (ADRB2) expressed on bronchial smooth muscle is a well-defined target for asthma treatment that has epidemiological implications in lung cancer development. And biochemical effect and pharmacogenetic relevance of regulatory and coding variants of ADRB2 have been well documented. Aiming to test whether the genetic variants of ADRB2 modify risk of lung AC, we compared the manifestation of three common single nucleotide polymorphisms (SNPs) of ADRB2 (G-1023A, G-654A, and A46G (Gly16Arg)) between 313 patients with lung AC and 321 controls. Overall association was not observed between risk and either individual of the three SNPs or their combined haplotypes. However, in the subgroup of young subjects < or =50 years old, significant association was observed for G-1023A (allele based OR, 1.82; 95% CI, 1.12-2.95), A46G (Gly16Arg) (allele based OR, 0.64; 95% CI, 0.40-1.03), and the haplotype A(-1023)A(46) (OR 2.62; 95% CI 1.30-5.27). Our results do not support a major independent role of ADRB2 polymorphisms in lung AC risk, suggesting that functional variants of other genes involved in the NNK epigenetic pathway of carcinogenesis should be investigated.
authors.affiliation: Laboratory of Systems Biology, Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Rd, Shanghai 200032, People's Republic of China.
authors.forename: Haijian
authors.initials: H
authors.lastname: Wang
authors.forename: Bingtao
authors.initials: B
authors.lastname: Hao
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
authors.forename: Naiqing
authors.initials: N
authors.lastname: Zhao
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Chengzhao
authors.initials: C
authors.lastname: Lin
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.forename: Daru
authors.initials: D
authors.lastname: Lu
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
mesh_terms: D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
chemical_list: D018343:Receptors, Adrenergic, beta-2