Sex differences in small cell lung cancer: Epidemiology and genetics

The incidence of small cell lung cancer (SCLC) in females has markedly increased over the last decades. However, sex differences in SCLC lack large database-based studies. The present study was aimed at exploring sex differences in SCLC. We used 18234 cases from the SEER database (1973-2015) to describe the epidemiologic feature of SCLC, and 120 cases from TCGA and two datasets from GEO databases to analyze genetic patterns of sex differences in SCLC. Survival analyses were conducted with log-rank tests and Cox proportional hazard models. Our results showed that female SCLC patients had smaller size of tumor, fewer metastasis, and lower stages in comparison to male patients, and females had significantly better OS and CSS than males with SCLC. Moreover, elder age, white race, large tumor size, advanced stage and distant metastasis were risk factors for mortality in both female and male SCLC patients. In SCLC, the expression levels of AMPH, GRIN2C and WNT4 were higher in males, and HOXA5 was more expressed in females. Notably, RB1 was more frequently mutated in female patients. We confirmed that female sex was associated with more favorable clinicopathological factors and better outcome of SCLC; Females and males also differed in gene expression levels, gene mutation frequency and types. This study highlights the need to consider sex as an important variable for improving SCLC diagnosis and treatment.