A Population-Based Study of Subsequent Primary Malignancies After Endometrial Cancer: Genetic, Environmental, and Treatment-Related Associations

Purpose To examine the risk of subsequent primary malignancies (SPMs) in women diagnosed with endometrial cancer. Methods and Materials The National Cancer Institute's Survival, Epidemiology, and End Results database was used to determine the risk of SPM after endometrial cancer in 69,739 women diagnosed between 1973 and 2005. Standardized incidence ratios were calculated (observed/expected [O/E]) for SPM sites. Results Median follow-up was 11.2 years, representing 757,567 person-years of follow-up. The risk of SPM was significantly increased for small intestine (O/E = 1.48; 99% confidence interval [CI], 1.03–2.05), colon (O/E = 1.16; CI, 1.09–1.24), vagina (O/E = 2.71; CI, 1.86–3.8), and urinary bladder (O/E = 1.41; CI, 1.25–1.59) SPMs and decreased for oral cavity and pharynx (O/E = 0.75; CI, 0.6–0.93), lung and bronchus (O/E = 0.78; CI, 0.72–0.84), and esophagus (O/E = 0.58; CI, 0.37–0.86) SPMs. Patients receiving external-beam radiotherapy for endometrial cancer had an increased risk of colon ( p p p = 0.04), and soft-tissue ( p = 0.014) SPMs. Patients treated with brachytherapy had an increased risk of bladder SPM ( p = 0.006). A positive bidirectional association with endometrial cancer was observed for colorectal cancer, with a negative bidirectional association for oropharyngeal and lung cancers. Conclusions Genetic, environmental, and treatment-related factors influence SPM risk. Genetic factors may contribute to the increased risk of colorectal cancer. Smoking's negative effect on endometrial cancer risk factors might explain the decreased risk of lung and oropharyngeal cancer. Patients treated with radiotherapy likely have a small but significantly increased risk of bladder, vagina, colon, and soft-tissue SPM.