Sex-Specific Expression of Gastrin-Releasing Peptide Receptor: Relationship to Smoking History and Risk of Lung Cancer

摘要: Background: Activation of gastrin-releasing peptide receptor (GRPR) in human airways has been associated with a proliferative response bronchial cells to and long-term tobacco use. The GRPR gene is located on the X chromosome escapes X-chromosome inactivation, which occurs females. Increasing evidence demonstrates that women are more susceptible than men carcinogenesis. We hypothesized susceptibility effects may be airway expression GRPR. Methods: analyzed messenger RNA (mRNA) lung tissues cultured from 78 individuals (40 males 38 females) fibroblasts exposed nicotine vitro. Nicotinic acetylcholine receptors were assayed by use radioactively labeled antagonists. A polymorphism exon 2 was used detect allele-specific mRNA some individuals. Statistical tests two-sided. Results: detected female male nonsmokers (55% versus 0%) short-term smokers (1‐25 pack-years [pack-years = number packs cigarettes smoked per day multiplied years smoking]) (75% 20%) (P .018 for nonsmoking smoking females males). Female exhibited at lower mean pack-year exposure (37.4 56.3 pack-years; P .037). Lung epithelial high-affinity, saturable nicotinic acetylcholine-binding sites. Expression elevated following nicotine. Conclusions: Our results suggest expressed frequently absence this activated earlier exposure. presence two copies factor increased tobacco-induced cancer. [J Natl Cancer Inst 2000;92:24‐33]