Sharon E Johnatty1, Yen Y Tan2, Daniel D Buchanan3, Michael Bowman1, Rhiannon J Walters1, Andreas Obermair4, Michael A Quinn5, Penelope B Blomfield6, Alison Brand7, Yee Leung8, Martin K Oehler9, Judy A Kirk10, Tracy A O'Mara1, Penelope M Webb11, Amanda B Spurdle12. 1. Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. 2. Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. 3. Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia; Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia. 4. Queensland Centre for Gynaecological Cancer, The University of Queensland, Queensland, Australia. 5. Department of Obstetrics and Gynaecology, Royal Women's Hospital, University of Melbourne, Melbourne, Victoria, Australia. 6. Department of Gynaecology Oncology, Royal Hobart Hospital, Hobart, Tasmania, Australia. 7. Department of Gynaecological Oncology, Westmead Hospital, University of Sydney, Westmead, New South Wales, Australia. 8. School of Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia. 9. Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia. 10. Familial Cancer Service, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney Medical School, University of Sydney Centre for Cancer Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia. 11. Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. 12. Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Electronic address: amanda.spurdle@qimrberghofer.edu.au.
Abstract
OBJECTIVE: To determine endometrial cancer (EC) risk according to family cancer history, including assessment by degree of relatedness, type of and age at cancer diagnosis of relatives. METHODS: Self-reported family cancer history was available for 1353 EC patients and 628 controls. Logistic regression was used to quantify the association between EC and cancer diagnosis in ≥1 first or second degree relative, and to assess whether level of risk differed by degree of relationship and/or relative's age at diagnosis. Risk was also evaluated for family history of up to three cancers from known familial syndromes (Lynch, Cowden, hereditary breast and ovarian cancer) overall, by histological subtype and, for a subset of 678 patients, by EC tumor mismatch repair (MMR) gene expression. RESULTS: Report of EC in ≥1 first- or second-degree relative was associated with significantly increased risk of EC (P=3.8×10-7), independent of lifestyle risk factors. There was a trend in increasing EC risk with closer relatedness and younger age at EC diagnosis in relatives (PTrend=4.43×10-6), and with increasing numbers of Lynch cancers in relatives (PTrend≤0.0001). EC risk associated with family history did not differ by proband tumor MMR status, or histological subtype. Reported EC in first- or second-degree relatives remained associated with EC risk after conservative correction for potential misreported family history (OR 2.0; 95% CI, 1.24-3.37, P=0.004). CONCLUSION: The strongest predictor of EC risk was closer relatedness and younger EC diagnosis age in ≥1 relative. Associations remained significant irrespective of proband MMR status, and after excluding MMR pathogenic variant carriers, indicating that Lynch syndrome genes do not fully explain familial EC risk.
OBJECTIVE: To determine endometrial cancer (EC) risk according to family cancer history, including assessment by degree of relatedness, type of and age at cancer diagnosis of relatives. METHODS: Self-reported family cancer history was available for 1353 EC patients and 628 controls. Logistic regression was used to quantify the association between EC and cancer diagnosis in ≥1 first or second degree relative, and to assess whether level of risk differed by degree of relationship and/or relative's age at diagnosis. Risk was also evaluated for family history of up to three cancers from known familial syndromes (Lynch, Cowden, hereditary breast and ovarian cancer) overall, by histological subtype and, for a subset of 678 patients, by EC tumor mismatch repair (MMR) gene expression. RESULTS: Report of EC in ≥1 first- or second-degree relative was associated with significantly increased risk of EC (P=3.8×10-7), independent of lifestyle risk factors. There was a trend in increasing EC risk with closer relatedness and younger age at EC diagnosis in relatives (PTrend=4.43×10-6), and with increasing numbers of Lynch cancers in relatives (PTrend≤0.0001). EC risk associated with family history did not differ by proband tumor MMR status, or histological subtype. Reported EC in first- or second-degree relatives remained associated with EC risk after conservative correction for potential misreported family history (OR 2.0; 95% CI, 1.24-3.37, P=0.004). CONCLUSION: The strongest predictor of EC risk was closer relatedness and younger EC diagnosis age in ≥1 relative. Associations remained significant irrespective of proband MMR status, and after excluding MMR pathogenic variant carriers, indicating that Lynch syndrome genes do not fully explain familial EC risk.
Authors: Tracy A O'Mara; Dylan M Glubb; Frederic Amant; Daniela Annibali; Katie Ashton; John Attia; Paul L Auer; Matthias W Beckmann; Amanda Black; Manjeet K Bolla; Hiltrud Brauch; Hermann Brenner; Louise Brinton; Daniel D Buchanan; Barbara Burwinkel; Jenny Chang-Claude; Stephen J Chanock; Chu Chen; Maxine M Chen; Timothy H T Cheng; Christine L Clarke; Mark Clendenning; Linda S Cook; Fergus J Couch; Angela Cox; Marta Crous-Bous; Kamila Czene; Felix Day; Joe Dennis; Jeroen Depreeuw; Jennifer Anne Doherty; Thilo Dörk; Sean C Dowdy; Matthias Dürst; Arif B Ekici; Peter A Fasching; Brooke L Fridley; Christine M Friedenreich; Lin Fritschi; Jenny Fung; Montserrat García-Closas; Mia M Gaudet; Graham G Giles; Ellen L Goode; Maggie Gorman; Christopher A Haiman; Per Hall; Susan E Hankison; Catherine S Healey; Alexander Hein; Peter Hillemanns; Shirley Hodgson; Erling A Hoivik; Elizabeth G Holliday; John L Hopper; David J Hunter; Angela Jones; Camilla Krakstad; Vessela N Kristensen; Diether Lambrechts; Loic Le Marchand; Xiaolin Liang; Annika Lindblom; Jolanta Lissowska; Jirong Long; Lingeng Lu; Anthony M Magliocco; Lynn Martin; Mark McEvoy; Alfons Meindl; Kyriaki Michailidou; Roger L Milne; Miriam Mints; Grant W Montgomery; Rami Nassir; Håkan Olsson; Irene Orlow; Geoffrey Otton; Claire Palles; John R B Perry; Julian Peto; Loreall Pooler; Jennifer Prescott; Tony Proietto; Timothy R Rebbeck; Harvey A Risch; Peter A W Rogers; Matthias Rübner; Ingo Runnebaum; Carlotta Sacerdote; Gloria E Sarto; Fredrick Schumacher; Rodney J Scott; V Wendy Setiawan; Mitul Shah; Xin Sheng; Xiao-Ou Shu; Melissa C Southey; Anthony J Swerdlow; Emma Tham; Jone Trovik; Constance Turman; Jonathan P Tyrer; Celine Vachon; David VanDen Berg; Adriaan Vanderstichele; Zhaoming Wang; Penelope M Webb; Nicolas Wentzensen; Henrica M J Werner; Stacey J Winham; Alicja Wolk; Lucy Xia; Yong-Bing Xiang; Hannah P Yang; Herbert Yu; Wei Zheng; Paul D P Pharoah; Alison M Dunning; Peter Kraft; Immaculata De Vivo; Ian Tomlinson; Douglas F Easton; Amanda B Spurdle; Deborah J Thompson Journal: Nat Commun Date: 2018-08-09 Impact factor: 14.919
Authors: Andreas Obermair; Eva Baxter; Donal J Brennan; Jessica N McAlpine; Jennifer J Muellerer; Frédéric Amant; Mignon D J M van Gent; Robert L Coleman; Shannon N Westin; Melinda S Yates; Camilla Krakstad; Monika Janda Journal: Obstet Gynecol Sci Date: 2020-07-08
Authors: Pik-Fang Kho; Frederic Amant; Daniela Annibali; Katie Ashton; John Attia; Paul L Auer; Matthias W Beckmann; Amanda Black; Louise Brinton; Daniel D Buchanan; Stephen J Chanock; Chu Chen; Maxine M Chen; Timothy H T Cheng; Linda S Cook; Marta Crous-Bous; Kamila Czene; Immaculata De Vivo; Joe Dennis; Thilo Dörk; Sean C Dowdy; Alison M Dunning; Matthias Dürst; Douglas F Easton; Arif B Ekici; Peter A Fasching; Brooke L Fridley; Christine M Friedenreich; Montserrat García-Closas; Mia M Gaudet; Graham G Giles; Ellen L Goode; Maggie Gorman; Christopher A Haiman; Per Hall; Susan E Hankinson; Alexander Hein; Peter Hillemanns; Shirley Hodgson; Erling A Hoivik; Elizabeth G Holliday; David J Hunter; Angela Jones; Peter Kraft; Camilla Krakstad; Diether Lambrechts; Loic Le Marchand; Xiaolin Liang; Annika Lindblom; Jolanta Lissowska; Jirong Long; Lingeng Lu; Anthony M Magliocco; Lynn Martin; Mark McEvoy; Roger L Milne; Miriam Mints; Rami Nassir; Geoffrey Otton; Claire Palles; Loreall Pooler; Tony Proietto; Timothy R Rebbeck; Stefan P Renner; Harvey A Risch; Matthias Rübner; Ingo Runnebaum; Carlotta Sacerdote; Gloria E Sarto; Fredrick Schumacher; Rodney J Scott; V Wendy Setiawan; Mitul Shah; Xin Sheng; Xiao-Ou Shu; Melissa C Southey; Emma Tham; Ian Tomlinson; Jone Trovik; Constance Turman; Jonathan P Tyrer; David Van Den Berg; Zhaoming Wang; Nicolas Wentzensen; Lucy Xia; Yong-Bing Xiang; Hannah P Yang; Herbert Yu; Wei Zheng; Penelope M Webb; Deborah J Thompson; Amanda B Spurdle; Dylan M Glubb; Tracy A O'Mara Journal: Int J Cancer Date: 2020-08-07 Impact factor: 7.396
Authors: Anthony Nguyen; John O'Dwyer; Thanh Vu; Penelope M Webb; Sharon E Johnatty; Amanda B Spurdle Journal: BMJ Open Date: 2020-06-11 Impact factor: 2.692
Authors: Sharon E Johnatty; Colin J R Stewart; Deborah Smith; Daniel Buchanan; Yee Leung; Martin K Oehler; Alison Brand; Penelope M Webb; Amanda B Spurdle Journal: Cancer Med Date: 2018-11-28 Impact factor: 4.452