Polymorphisms in genes of the steroid hormone biosynthesis and metabolism pathways and endometrial cancer risk |
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| Authors: | Katie A. Ashton Anthony Proietto Geoffrey Otton Ian Symonds Mark McEvoy John Attia Michael Gilbert Ute Hamann Rodney J. Scott |
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| Affiliation: | 1. Discipline of Medical Genetics, School of Biomedical Sciences, Faculty of Health, University of Newcastle, Australia and the Hunter Medical Research Institute, NSW 2308, Australia;2. Hunter Centre for Gynaecological Cancer, John Hunter Hospital, Newcastle, NSW 2305, Australia;3. School of Medicine and Public Health, Faculty of Health, University of Newcastle, NSW 2305, Australia;4. Molecular Genetics of Breast Cancer, German Cancer Research Center, Heidelberg 69120, Germany;5. Division of Genetics, Hunter Area Pathology Service, John Hunter Hospital, Newcastle, NSW 2305, Australia;1. Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden;2. Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden;3. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway;4. Department of Endocrinology, Trondheim University Hospital, Trondheim, Norway;5. CALAB Research, Stockholm, Sweden;6. Medical Evidence & Observational Research, Global Medicines Development AstraZeneca, United Kingdom;1. Faculty of Medicine, University of Montreal, Quebec, Canada;2. Department of Obstetrics and Gynecology, University of Montreal, Quebec, Canada;3. ART-PGD Center, CHU Sainte-Justine, Montreal, Quebec, Canada;4. Division of Pediatric and Adolescent Gynecology, CHU Sainte-Justine, Montreal, Quebec, Canada;1. Department of Urology, Tung''s Taichung MetroHarbor Hospital, Taichung County, Taiwan, ROC;2. Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan, ROC;3. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC;4. Department of Urology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, ROC;5. Department of Urology, Chia-Yi Christian Hospital, Chiayi, Taiwan, ROC;6. Tainan University of Technology, Tainan, Taiwan, ROC;7. Department of Urology, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC;8. School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, ROC;1. Experimental Cardiology Laboratory, University Medical Center Utrecht, Utrecht, The Netherlands;2. Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands;3. Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands;4. Julius Center of Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands;5. Department of Surgery and Cardiovascular Research Institute, NUS & NUHS, Singapore;1. International Medical Centre, Chinese PLA General Hospital, Beijing, China;2. Human Centrifuge Medical Training Base of Institute of Aviation Medicine, Air Force, Beijing, China;3. First Geriatric Cardiology Department, Chinese PLA General Hospital, Beijing, China;4. Shaoxing Women and Children''s Hospital, Shaoxing City, China;5. Medical School of Zhejiang University, Hangzhou City, China |
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| Abstract: | Objectives: The incidence of endometrial cancer has recently increased substantially and studies have shown that altered levels of exogenous and endogenous hormones are associated with individual variation in endometrial cancer risk. The environmental and reproductive risk factors that influence these hormones are well known, however, genetic variants involved in hormone biosynthesis and estrogen metabolism have not been well established in endometrial cancer. Methods: To determine whether polymorphisms in genes of the steroid hormone biosynthesis and metabolism pathways are associated with endometrial cancer risk, 28 polymorphisms in 18 genes were genotyped in 191 endometrial cancer cases and 291 healthy controls. Results: The GSTM1 deletion and the variant (GG) genotype of the CYP1B1 rs1800440 polymorphism were associated with a decreased risk of developing endometrial cancer. Furthermore, combinations of haplotypes in CYP1A1, CYP1B1 and GSTs were associated with a decreased risk. The analysis of the repeat polymorphisms revealed that women with the long repeat allele length of the ESR1 (GT)n repeat polymorphism were at an increased risk of developing endometrial cancer. Conversely, women with two long repeat length alleles of the (CAG)n repeat polymorphism in the AR correlated with a decrease in endometrial cancer risk compared to women with one or two alleles with the short repeat length. Conclusions: The findings are consistent with our hypothesis that variability in genes involved in steroidogenesis and estrogen metabolism may alter the risk of developing endometrial cancer, suggesting that they may be useful as biomarkers for genetic susceptibility to endometrial cancer. |
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