Estrogen Receptor May Play Important Role in Gender Differences of Early-Onset Colorectal Cancer

The incidence of early-onset colorectal cancer (EOCRC) is increasing year by year. However, it is still unclear and controversial whether there is a significant gender difference. Our aims to investigate the clinicopathological characteristics of EOCRC, especially gender differences, and their correlation with the expression of estrogen receptor (ER), so as to provide a scientific basis for optimizing the early screening and treatment strategy of EOCRC.

All surgical specimens of CRC were collected from January 2015 to July 2024. Then, the clinicopathological characteristics were analyzed between EOCRC and late-onset CRC (LOCRC). Simultaneously, the expression of ER was investigated in EOCRC by RT-PCR and immunohistochemical staining.

A total of 3041 CRC cases were analyzed in this study, which included 485 EOCRC and 2556 LOCRC cases. Specifically, EOCRC had significant differences in gender (P = .0356), deficient mismatch repair (dMMR) status (P = .0029), and lymph node metastases (P = .0425) compared with LOCRC. Simultaneously, in EOCRC, males were more susceptible to colon cancer (P = .0009) and dMMR status (P = .0365) compared with females. Moreover, the variation of dMMR status was related to the absence of genetic history of disease (P = .0034). Totally, the expression of ER mRNA was higher in female CRC than that in male one (P = .0009), which was also in EOCRC (P = .0092). In addition, its expression was higher in LOCRC (P = .0056) and female LOCRC with dMMR (dLOF) (P = .0341) than that in EOCRC and female EOCRC with dMMR (dEOF). Further analysis showed that the expression of ER mRNA was significantly higher in male LOCRC (LOM) (P = .0305), LOCRC with dMMR (dLO) (P = .0030), male LOCRC with dMMR (dLOM) (P = .0275), and sporadic LOM (dLOM-s) (P = .0274) than that in their corresponding male EOCRC (EOM), EOCRC with dMMR (dEO), male EOCRC with dMMR (dEOM), and sporadic dEOM (dEOM-s) in turn, but there was no significant difference in proficient MMR (pMMR) (P = .6046).

There were significant differences in the clinicopathological features and sex hormone expression in EOCRC with different genders, suggesting that gender may be an independent factor in clinical classification of EOCRC.