Gastrin-releasing peptide receptor expression in non-cancerous bronchial epithelia is associated with lung cancer: a case-control study

Ann Marie Egloff,James D Luketich,Autumn Gaither Davis,Joseph M Pilewski,Rodney Landreneau,Yongli Shuai,Stephanie Land,York E Miller,Jennifer R Grandis,Jill M Siegfried

doi:10.1186/1465-9921-13-9

Ann Marie Egloff, James D Luketich + Show 8 more

Open Access

https://doi.org/10.1186/1465-9921-13-9

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Abstract

BackgroundNormal bronchial tissue expression of GRPR, which encodes the gastrin-releasing peptide receptor, has been previously reported by us to be associated with lung cancer risk in 78 subjects, especially in females. We sought to define the contribution of GRPR expression in bronchial epithelia to lung cancer risk in a larger case-control study where adjustments could be made for tobacco exposure and sex.MethodsWe evaluated GRPR mRNA levels in histologically normal bronchial epithelial cells from 224 lung cancer patients and 107 surgical cancer-free controls. Associations with lung cancer were tested using logistic regression models.ResultsBronchial GRPR expression was significantly associated with lung cancer (OR = 4.76; 95% CI = 2.32-9.77) in a multivariable logistic regression (MLR) model adjusted for age, sex, smoking status and pulmonary function. MLR analysis stratified by smoking status indicated that ORs were higher in never and former smokers (OR = 7.74; 95% CI = 2.96-20.25) compared to active smokers (OR = 1.69; 95% CI = 0.46-6.33). GRPR expression did not differ by subject sex, and lung cancer risk associated with GRPR expression was not modified by sex.ConclusionsGRPR expression in non-cancerous bronchial epithelium was significantly associated with the presence of lung cancer in never and former smokers. The association in never and former smokers was found in males and females. Association with lung cancer did not differ by sex in any smoking group.

Highlights

Normal bronchial tissue expression of GRPR, which encodes the gastrin-releasing peptide receptor, has been previously reported by us to be associated with lung cancer risk in 78 subjects, especially in females
GRPR expression in bronchial epithelia was more frequent in lung cancer patients than cancer-free control subjects Presence or absence of GRPR mRNA in non-cancerous bronchial epithelial cells derived from mainstem bronchus airway biopsies of lung cancer cases (n = 224) and cancer-free controls (n = 107) (Table 1) was assessed by reverse transcription (RT)-PCR followed by hybridization with a radio-labeled probe in order to maximize sensitivity
Because the airway biopsy analysis of this cohort began before quantitative PCR (q-PCR) was available, the RT-PCR semi-quantitative technique was used throughout the lung cancer case-control study to maintain consistency and power

Summary

Introduction

Normal bronchial tissue expression of GRPR, which encodes the gastrin-releasing peptide receptor, has been previously reported by us to be associated with lung cancer risk in 78 subjects, especially in females. Our group previously reported that bronchial epithelium expression of GRPR, which encodes the gastrin-releasing peptide receptor (GRPR), was associated with a diagnosis of lung cancer in female never smokers [2]. This finding raised the possibility that increased GRPR expression in women accounted for some of the increased incidence rates of lung cancer in never smokers who are female, compared to never smoking men, which was recently reported in a large prospective cohort study [4]. Since GRPR stimulation induces proliferative effects in bronchial cells [5], it is possible that activation of this pathway is a risk factor for lung cancer separate from that of tobacco exposure

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