Somatic profile in lung cancers is associated to reproductive factors in never-smokers women: Results from the IFCT-1002 BioCAST study

Respir Med Res. 2020 Mar:77:58-66. doi: 10.1016/j.resmer.2020.01.003. Epub 2020 Jan 31.

Abstract

Background: Lung cancer in women is on the rise, with a higher proportion occurring in lifelong never-smokers. Lung cancer in never-smokers (LCINS) exhibits a high frequency of driver oncogene alterations. In this study, we aimed to investigate whether exposure to reproductive factors in women with LCINS may modulate the molecular pattern.

Methods: All newly diagnosed LCINSs were included in a prospective, observational study (IFCT-1002 BioCAST). Each patient responded to a questionnaire including reproductive factors. Biomarker test results were also collected.

Results: Two hundred and sixty women were included in this analysis, and 166 alterations were characterized. EGFR mutation frequency proved greater among patients with late menarche (74% in age>14 vs. 40% and 41% for 12-14 and ≤12 years, respectively; P=0.020) and tended to decrease with increasingly late age at menopause. In multivariate analysis, EGFR mutation frequency increased by 23% per increment of 1 year of age at menarche (P=0.048), and by 9% for each year at age at first birth (P=0.035). ALK alteration frequency was greater in women with high parity (50% in≥5 vs. 12% and 7% for 1-4 and nulliparity, respectively; P=0.021).

Conclusion: In a cohort of women LCINSs, female hormonal factors appear to impact molecular pattern.

Keywords: Female hormonal factors; Lung cancer; Never-smoker; Oncogenic drivers.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anaplastic Lymphoma Kinase / genetics
  • Cohort Studies
  • DNA Mutational Analysis
  • ErbB Receptors / genetics
  • Female
  • France / epidemiology
  • Gene Frequency
  • Humans
  • Lung Neoplasms / complications
  • Lung Neoplasms / epidemiology*
  • Lung Neoplasms / genetics*
  • Middle Aged
  • Oncogenes / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Reproductive History*
  • Risk Factors
  • Smokers / statistics & numerical data

Substances

  • KRAS protein, human
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)