Sex-specificity in lung cancer risk

Int J Cancer. 2020 May 1;146(9):2376-2382. doi: 10.1002/ijc.32716. Epub 2019 Nov 1.


Smoking is indisputably linked to lung cancer, yet only a small fraction of smokers develops this disease. Although previously tobacco-derived carcinogens and enzyme polymorphisms have been identified to increase the risk for smokers, recent epidemiological data suggest even sex-specificity as a new and additional factor. Obviously, women have a higher risk to develop lung cancer upon smoking than men. Overall, the odds ratio to develop lung cancer was almost three times greater for women than for men, DNA adduct levels were higher among females than in males and mutations in the tumor suppressor gene p53 and the proto-oncogene K-RAS were more frequently found in women than in men. A growing number of studies suggest that the interaction between tobacco carcinogens and endogenous and exogenous sex steroids may be important. Women taking hormone replacement therapy (HRT) or oral contraceptives experienced to have an increased lung cancer incidence. Epidemiologic data on HRT show a significant association between both a younger median age at lung cancer diagnosis and a shorter median survival time. Another clue is the significantly higher number of lung cancer diagnosed women who are largely premenopausal in comparison to diagnosed men in the same age or women with shorter menstrual cycles. Finally, the Coronary Drug Project (men who received estrogen preparations to reduce future cardiac events) was stopped when increased lung cancer mortality was observed in the estrogen therapy group. The present review provides a short overview and discussion on lung cancer risk and the impact thereon of sex.

Keywords: lung cancer; sex differences; tobacco smoking.

Publication types

  • Review

MeSH terms

  • Carcinogens / toxicity
  • Female
  • Hormone Replacement Therapy / adverse effects
  • Humans
  • Incidence
  • Lung Neoplasms / epidemiology*
  • Lung Neoplasms / etiology*
  • Lung Neoplasms / pathology
  • Male
  • Proto-Oncogene Mas
  • Proto-Oncogenes / genetics
  • Risk Factors
  • Sex Factors
  • United States / epidemiology


  • Carcinogens
  • MAS1 protein, human
  • Proto-Oncogene Mas