J Gynecol Oncol.
2018 May;29(3):e39. 10.3802/jgo.2018.29.e39.
Endometrial cancer risk and survival by tumor MMR status
- Nagle CM
- O'Mara TA
- Tan Y
- Buchanan D
- Obermair A
- Blomfield
- Quinn MA
- Webb PM
- Spurdle AB
- on behalf of the Australian Endometrial Cancer Study Group
- Affiliations
-
- 1Population Health Department, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Australia. christina.nagle@qimrberghofer.edu.au
- 2School of Public Health, University of Queensland, Brisbane, Australia.
- 3Genetics & Computational Biology Department, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Australia.
- 4Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Australia.
- 5Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Australia.
- 6Genetic Medicine & Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, Australia.
- 7Queensland Centre of Gynaecological Research, Royal Brisbane and Women's Hospital, Herston, Australia.
- 8Faculty of Medicine, The University of Queensland, Brisbane, Australia.
- 9Department of Gynaecology Oncology, Royal Hobart Hospital, Hobart, Australia.
- 10Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Australia.
- KMID: 2409940
- DOI: http://doi.org/10.3802/jgo.2018.29.e39
Abstract
OBJECTIVE
The risk of developing endometrial cancer (EC) and/or survival following a diagnosis of EC might differ by tumor DNA mismatch repair (MMR) status. We assessed the association between tumor MMR status (classified as MMR-proficient, somatic MMR-deficient, germline MMR-deficient) and the risk of developing EC and survival following a diagnosis of EC.
METHODS
We analyzed data from women who participated in the Australian National Endometrial Cancer Study (ANECS) conducted between 2005 and 2007. Risk analyses (698 cases/691 population controls) utilized sociodemographic and lifestyle information obtained from telephone interviews at recruitment. For survival analyses (728 cases), patients' clinical data was abstracted from medical records, and survival data were obtained via linkage with the Australian National Death Index. We used logistic regression analysis to evaluate the associations between tumor MMR status and EC risk, and proportional hazards models to perform survival analyses with adjustment of known prognostic factors.
RESULTS
Established risk factors for EC did not differ significantly by tumor MMR status. In analyses including all EC subtypes, overall and EC-specific survival did not differ by tumor MMR status. Among women with the most common endometrioid subtype, EC-specific survival was worse for women with somatic MMR-deficient EC compared to women with MMR-proficient EC (hazard ratio [HR]=2.18; 95% confidence interval [CI]=1.19-4.01).
CONCLUSION
The risk of EC is not associated with MMR status. Accurate separation of germline from somatic causes of MMR deficiency suggests that patients with endometrioid subtype somatic MMR-deficient tumors have poorer EC-specific survival than those with MMR-proficient tumors, after accounting for other prognostic factors.
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