Synchronous Multiple Lung Adenocarcinomas: Estrogen Concentration in Peripheral Lung

PLoS One. 2016 Aug 15;11(8):e0160910. doi: 10.1371/journal.pone.0160910. eCollection 2016.

Abstract

Background: The detection rate of synchronous multiple lung adenocarcinomas (SMLA), which display multiple ground glass opacity nodules in the peripheral lung, is increasing due to advances in high resolution computed tomography. The backgrounds of multicentric development of adenocarcinoma are unknown. In this study, we quantitated estrogen concentration in the peripheral lungs of postmenopausal female patients with SMLA.

Methods: The tissue concentration of estrogens (estrone [E1] and estdadiol [E2]) in the noncancerous peripheral lung were measured with liquid chromatography/electrospray tandem mass spectrometry in postmenopausal female patients with lung adenocarcinoma. The expression levels of CYP19A1 in the normal lung were also quantitated with real-time PCR. Thirty patients with SMLA and 79 cases of control patients with single lung adenocarcinoma were analyzed.

Results: The concentrations of E1 and E2 in the noncancerous tissue were significantly higher in SMLA cases than control cases (P = 0.004 and P = 0.02, respectively). The minor allele (A) of single nucleotide polymorphism rs3764221 were significantly associated with higher concentration of E1 and E2 (P = 0.002 and P = 0.01, respectively) and higher CYP19A1 mRNA expression (P = 0.03).

Conclusion: The tissue estrogen concentration of peripheral lung was significantly higher in SMLA than control cases. The high concentration of estrogen may be one of the causes of multicentric development of peripheral lung adenocarcinomas.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma of Lung
  • Aged
  • Aromatase / genetics
  • Estrogens / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung / metabolism*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Estrogens
  • RNA, Messenger
  • Aromatase
  • CYP19A1 protein, human

Grants and funding

This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, Culture and Technology of Japan (23592069) (24592096) and by a grant from the Smoking Research Foundation (2012-2015). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.