Molecular Epidemiological Study on Passive Smoking and Estrogen Receptor Expression in Never-smokers with Non-small Cell Lung Cancer

Osaka City Med J. 2016 Dec;62(2):77-84.

Abstract

Background: Although sex hormones are thought to play an important role in the carcinogenesis of non-small cell lung cancer (NSCLC) in never-smokers, the causative mechanism remains unknown. Passive smoking (PS) is common among East Asian women and has been suggested to be a potential cause of the disease.

Methods: We systematically evaluated the expression of estrogen receptor (ER), the prevalence of PS, and genetic mutations using tumor samples from a prospectively registered cohort of never-smokers with lung cancer. The study enrolled 92 never-smokers with NSCLC. Expression of ERa, ERP, and progesterone receptor (PR) was examined via immunohistochemical staining (IHC). Detailed PS information was obtained through a standardized questionnaire. The cumulative dose of PS (CPS) was evaluated as a sum of the number of exposure years at home and/or in the work place.

Results: Nuclear expression of ERa, ERP, and PR was detected in 0, 14, and 3 cases, respectively. ERP was more frequently overexpressed in earlier stage cancer (p=0.043). Ninety patients (97.9%) had a PS history, and the median CPS was 47.5 years (range, 0-103 years). There was no significant correlation between the amount of PS -and ERP expression (p=0.101). Twelve patients (85.7%) had Epidermal growth factor receptor ,EGFR) mutations in 14 .tumors expressing ERP, and a trend towards an association between ERP expression and EGFR mutations (p =0.067) was -observed.

Conclusions: Nuclear expression of ERP was more frequently observed in early stage NSCLC in never-smokers.

MeSH terms

  • Aged
  • Carcinoma, Non-Small-Cell Lung* / epidemiology
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Correlation of Data
  • ErbB Receptors / genetics
  • Estrogen Receptor alpha / genetics*
  • Estrogen Receptor beta / genetics*
  • Gene Expression Profiling / methods
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Receptors, Progesterone / genetics*
  • Tobacco Smoke Pollution / analysis*

Substances

  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Receptors, Progesterone
  • Tobacco Smoke Pollution
  • EGFR protein, human
  • ErbB Receptors