Rajani Bharati1, Mark A Jenkins1, Noralane M Lindor2, Loïc Le Marchand3, Steven Gallinger4, Robert W Haile5, Polly A Newcomb6, John L Hopper1, Aung Ko Win7. 1. Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia. 2. Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ, USA. 3. University of Hawaii Cancer Center, Honolulu, HI, USA. 4. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Cancer Care Ontario, Toronto, Ontario, Canada. 5. Department of Medicine, Division of Oncology, Stanford University, CA, USA. 6. Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 7. Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: awin@unimelb.edu.au.
Abstract
OBJECTIVE: To determine whether risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair (MMR) gene depends on family history of endometrial or colorectal cancer. METHODS: We retrospectively followed a cohort of 79,166 women who were recruited to the Colon Cancer Family Registry, after exclusion of women who were relatives of a carrier of a MMR gene mutation. The Kaplan-Meier failure method was used to estimate the cumulative risk of endometrial cancer. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for association between family history of endometrial or colorectal cancer and risk of endometrial cancer. RESULTS: A total of 628 endometrial cancer cases were observed, with mean age at diagnosis of 54.4 (standard deviation: 15.7) years. The cumulative risk of endometrial cancer to age 70 years was estimated to be 0.94% (95% CI 0.83-1.05) for women with no family history of endometrial cancer, and 3.80% (95% CI 2.75-4.98) for women with at least one first- or second-degree relative with endometrial cancer. Compared with women without family history, we found an increased risk of endometrial cancer for women with at least one first- or second-degree relative with endometrial cancer (HR 3.66, 95% CI 2.63-5.08), and for women with one first-degree relative with colorectal cancer diagnosed at age <50 years (HR 1.48, 95% CI 1.15-1.91). CONCLUSION: An increased risk of endometrial cancer is associated with a family history of endometrial cancer or early-onset colorectal cancer for women without a MMR gene mutation, indicating for potential underlying genetic and environmental factors shared by colorectal and endometrial cancers other than caused by MMR gene mutations.
OBJECTIVE: To determine whether risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair (MMR) gene depends on family history of endometrial or colorectal cancer. METHODS: We retrospectively followed a cohort of 79,166 women who were recruited to the Colon Cancer Family Registry, after exclusion of women who were relatives of a carrier of a MMR gene mutation. The Kaplan-Meier failure method was used to estimate the cumulative risk of endometrial cancer. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for association between family history of endometrial or colorectal cancer and risk of endometrial cancer. RESULTS: A total of 628 endometrial cancer cases were observed, with mean age at diagnosis of 54.4 (standard deviation: 15.7) years. The cumulative risk of endometrial cancer to age 70 years was estimated to be 0.94% (95% CI 0.83-1.05) for women with no family history of endometrial cancer, and 3.80% (95% CI 2.75-4.98) for women with at least one first- or second-degree relative with endometrial cancer. Compared with women without family history, we found an increased risk of endometrial cancer for women with at least one first- or second-degree relative with endometrial cancer (HR 3.66, 95% CI 2.63-5.08), and for women with one first-degree relative with colorectal cancer diagnosed at age <50 years (HR 1.48, 95% CI 1.15-1.91). CONCLUSION: An increased risk of endometrial cancer is associated with a family history of endometrial cancer or early-onset colorectal cancer for women without a MMR gene mutation, indicating for potential underlying genetic and environmental factors shared by colorectal and endometrial cancers other than caused by MMR gene mutations.
Authors: Melissa C Southey; Mark A Jenkins; Leeanne Mead; Jonathan Whitty; Melanie Trivett; Andrea A Tesoriero; Letitia D Smith; Kim Jennings; Garry Grubb; Simon G Royce; Michael D Walsh; Melissa A Barker; Joanne P Young; Jeremy R Jass; D James B St John; Finlay A Macrae; Graham G Giles; John L Hopper Journal: J Clin Oncol Date: 2005-08-22 Impact factor: 44.544
Authors: P Benatti; R Sassatelli; L Roncucci; M Pedroni; R Fante; C Di Gregorio; L Losi; R Gelmini; M Ponz de Leon Journal: Int J Cancer Date: 1993-05-28 Impact factor: 7.396
Authors: Paul J Goodfellow; Caroline C Billingsley; Heather A Lankes; Shamshad Ali; David E Cohn; Russell J Broaddus; Nilsa Ramirez; Colin C Pritchard; Heather Hampel; Alexis S Chassen; Luke V Simmons; Amy P Schmidt; Feng Gao; Louise A Brinton; Floor Backes; Lisa M Landrum; Melissa A Geller; Paul A DiSilvestro; Michael L Pearl; Shashikant B Lele; Matthew A Powell; Richard J Zaino; David Mutch Journal: J Clin Oncol Date: 2015-11-09 Impact factor: 44.544