Sex-Based Differences in Lung Cancer Incidence: A Retrospective Analysis of Two Large US-Based Cancer Databases

Abstract

Background/Objectives: Non-small cell lung cancer (NSCLC) has seen a relative rise in incidence among females versus males in recent years, although males still have a higher overall incidence. However, it is unclear whether this trend is consistent across all populations. Therefore, we retrospectively examined this relationship in two large high-risk clinical cohorts. Methods: First, we analyzed lung cancer incidence among individuals with a smoking history of over 40 pack-years in the National Lung Screening Trial (NLST). Then, we investigated the incidence of second primary NSCLC in patients who underwent lobectomy for previous stage I lung cancer using the Surveillance, Epidemiology, and End Results (SEER) database. We performed both univariate and multivariable time-to-event analyses to investigate the relationship between sex and lung cancer incidence. Results: In the NLST cohort (n = 37,627), females had a higher risk of developing primary NSCLC than males (HR = 1.11 [1.007-1.222], p = 0.035) after adjusting for age and pack-year history. In the SEER cohort (n = 19,327), females again exhibited an increased risk of developing a second primary lung cancer (HR = 1.138 [1.02-1.269], p = 0.021), after adjusting for age, race, grade, and histology. Conclusions: Our analysis reveals that females have a modestly higher lung cancer incidence than males in high-risk populations. These findings underscore the importance of further researching the underlying cellular processes that may cause sex-specific differences in lung cancer incidence.

Keywords: NLST; NSCLC; SEER; lung cancer incidence; sex disparities.

Figure 1

Study Selection Criteria. (A)—selection criteria for the NLST database. (B)—selection criteria for the SEER database.

Figure 2

Multivariate Cox Regression Graphs for both the NLST and SEER Databases. (A) Multivariable cox proportional hazards model for time to primary lung cancer in the NLST database. Final model includes sex, age, and number of pack-years. (B) Multivariable cox proportional hazards model for second primary lung cancer in the SEER database. Final model includes sex and histopathology.