A population-based study of subsequent primary malignancies after endometrial cancer: genetic, environmental, and treatment-related associations.
OBJECTIVE
To examine the risk of subsequent primary malignancies (SPMs) in women diagnosed with endometrial cancer.


METHODS
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 < 0.001), bladder (p < 0.001), vagina (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.
Brown
Aaron P
AP
Department of Radiation Oncology, University of Utah, Salt Lake City, UT 84112, USA.
Neeley
E Shannon
ES
Werner
Theresa
T
Soisson
Andrew Patrick
AP
Burt
Randall W
RW
Gaffney
David K
DK
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007414:Intestinal Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D007421:Intestine, Small / Q000528:radiation effects; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D010610:Pharyngeal Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D018570:Risk Assessment; D018426:SEER Program; D014481:United States / Q000453:epidemiology; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D014625:Vaginal Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D055815:Young Adult