Key reproductive factors, including early menarche, early menopause, and a shortened reproductive life span, are associated with higher risks of lung cancer among women, according to a new study. These findings, which were recently presented during the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer 2023 in Singapore, underscore the importance of screening reproductive factors as a preventive measure.
"In 2018, 2.09 million new cases of lung cancer (11.6% of all cancer cases) and 1.76 million deaths (18.4% of all cancer deaths) were estimated by GLOBOCAN," noted study author Yan Zhang, MD, PhD, from Xiangya Hospital at the Central South University in Changsha, China, during a press briefing. "Female nonsmokers were approximately 3 times more susceptible to developing lung cancer than male nonsmokers. Hormonal and reproductive factors were thought to be involved in the occurrence of lung cancer in women. However, these findings have been far from consistent across studies."
Methods & Findings
Recognizing the need for further investigation, Zhang and colleagues initiated a prospective, cohort study using data from the UK Biobank to examine associations between individual reproductive factors and the risk of developing lung cancer. Furthermore, the researchers conducted subgroup analyses stratified by a number of factors, including age, smoking status, body mass index, genetic risk, and histological subtypes.
The primary endpoint of this study was lung cancer (ICD-10 codes C33 and C34), Zhang explained, while also noting that multiple reproductive factors were estimated. This included the following: age at menarche and menopause, reproductive life span, age at first live birth, the number of live births, stillbirths, miscarriages and abortions, the history of hysterectomy and/or oophorectomy, as well as exogenous hormone exposures such as the administration of oral contraceptive pills and hormone replacement therapy. A total of 273,190 female participants were enrolled in the study, and 1,182 cases of new-onset lung cancer were recorded over a median follow-up period of 12 years.
When discussing baseline characteristics of the study population, Zhang noted that participants diagnosed with lung cancer were older, had a lower educational background, and were also more likely to be current smokers.
"In terms of reproductive factors, women with incident lung cancer were accompanied by an earlier age at menarche and menopause, a shorter reproductive span, an earlier age at first live birth, as well as a lower likelihood of oral contraceptive pill use and a greater exposure to hormone replacement therapy," she said.
Multivariable-adjusted models revealed several reproductive factors are associated with an increased risk of incident lung cancer among women. This included early menarche (age <= 11 years), early menopause (age <= 46 years or age of 47-49 years), a shorter reproductive span (age <= 32 years or age of 33-35 years), and early age at first birth (<= 20 years or age of 21-25 years). Additionally, Zhang reported that a number of reproductive factors, particularly early menopause, shortened reproductive span, and early age at first birth, had "substantially stronger association with elevated risk of lung cancer, particularly non-small cell lung cancer, in those populations with a high genetic risk and more detrimental behaviors."
Study Conclusions
This prospective cohort study, which sheds light on the connection between reproductive factors and lung cancer risk, is strengthened by a large sample size and more than 10 years of follow-up, according to Zhang.
"We are also the first to incorporate genetic susceptibility for stratification," she noted. "[Additionally,] choosing an appropriate population as the reference could avoid some potential bias."
However, Zhang acknowledged this research does have some limitations, including recall bias and misclassification for reproductive factors. The study only involved females of European ancestry, which may limit the interpretation and external validity of the findings into other populations.
"Most women who had undergone oophorectomy and/or hysterectomy were also given HRT, so it was very difficult to attribute the effect on lung cancer by an individual factor," she stated, while also highlighting other unmeasured confounding factors, such as outdoor and indoor air pollution or healthy bias of the population.
"These findings are of paramount importance in our understanding of the potential risk factors for lung cancer among women," noted Zhang, while discussing the significance of this research in a statement. "Early menarche, early menopause, and a shortened reproductive life span are associated with higher risks of incident lung cancer, especially NSCLC, in subpopulations with specific genetic risk and lifestyle choices. By understanding these associations, health care professionals can develop targeted preventive strategies and interventions to combat lung cancer effectively," she concluded.
Catlin Nalley is a contributing writer.