Frederick S Albright1, Wendy Kohlmann2, Leigh Neumayer3,4, Saundra S Buys2,5, Cindy B Matsen2,5, Kimberly A Kaphingst2,6, Lisa A Cannon-Albright7,8,9. 1. Department of Pharmacotherapy, University of Utah College of Pharmacy, Salt Lake City, UT, USA. 2. Huntsman Cancer Institute, University of Utah Health Sciences Center, 391 Chipeta Way, Suite D, Salt Lake City, UT, 84108, USA. 3. Department of Surgery, University of Utah School of Medicine, Salt Lake City, USA. 4. Department of Surgery, University of Arizona College of Medicine, Tucson, AZ, USA. 5. Division of Oncology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA. 6. Department of Communication, University of Utah College of Humanities, Salt Lake City, UT, USA. 7. Huntsman Cancer Institute, University of Utah Health Sciences Center, 391 Chipeta Way, Suite D, Salt Lake City, UT, 84108, USA. lisa.albright@utah.edu. 8. Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA. lisa.albright@utah.edu. 9. George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT, USA. lisa.albright@utah.edu.
Abstract
PURPOSE: Using a large resource linking genealogy with decades of cancer data, a non-traditional approach was used to estimate individualized risk for breast cancer (BC) based on specific family history extending to first cousins, providing a clearer picture of the contribution of various aspects of both close and distant combinations of affected relatives. METHODS: RRs for BC were estimated in 640,366 females for a representative set of breast cancer family history constellations that included number of first- (FDR), second-(SDR), and third-degree relatives (TDR), maternal and paternal relatives, and age at earliest diagnosis in a relative. RESULTS: RRs for first-degree relatives of BC cases ranged from 1.61 (= 1 FDR affected, CI 1.56, 1.67) to 5.00 (≥ 4 FDRs affected, CI 3.35, 7.18). RRs for second-degree relatives of probands with 0 affected FDRs ranged from 1.04 (= 1 SDR affected, CI 1.00, 1.08) to 1.71 (≥ 4 SDRs affected, CI 1.26, 2.27) and for second-degree relatives of probands with exactly 1 FDR from 1.54 (0 SDRs affected, CI 1.47, 1.61) to 4.78 (≥ 5 SDRs; CI 2.47, 8.35). RRs for third-degree relatives with no closer relatives affected were significantly elevated over population risk for probands with ≥ 5 affected TDRs RR = 1.32, CI 1.11, 1.57). CONCLUSIONS: The majority of females in the Utah resource had a positive family history of BC in FDRs to TDRs. Presence of any number of affected FDRs or SDRs significantly increased risk for BC over population risk; and more than four TDRs, even with no affected FDRs or SDRs, significantly increased risk over population risk. Risk prediction derived from the specific and extended family history constellation of affected relatives allows identification of females at increased risk even when they do not have a conventionally defined high-risk family; these risks could be a powerful, efficient tool to individualize cancer screening and prevention.
PURPOSE: Using a large resource linking genealogy with decades of cancer data, a non-traditional approach was used to estimate individualized risk for breast cancer (BC) based on specific family history extending to first cousins, providing a clearer picture of the contribution of various aspects of both close and distant combinations of affected relatives. METHODS: RRs for BC were estimated in 640,366 females for a representative set of breast cancer family history constellations that included number of first- (FDR), second-(SDR), and third-degree relatives (TDR), maternal and paternal relatives, and age at earliest diagnosis in a relative. RESULTS: RRs for first-degree relatives of BC cases ranged from 1.61 (= 1 FDR affected, CI 1.56, 1.67) to 5.00 (≥ 4 FDRs affected, CI 3.35, 7.18). RRs for second-degree relatives of probands with 0 affected FDRs ranged from 1.04 (= 1 SDR affected, CI 1.00, 1.08) to 1.71 (≥ 4 SDRs affected, CI 1.26, 2.27) and for second-degree relatives of probands with exactly 1 FDR from 1.54 (0 SDRs affected, CI 1.47, 1.61) to 4.78 (≥ 5 SDRs; CI 2.47, 8.35). RRs for third-degree relatives with no closer relatives affected were significantly elevated over population risk for probands with ≥ 5 affected TDRs RR = 1.32, CI 1.11, 1.57). CONCLUSIONS: The majority of females in the Utah resource had a positive family history of BC in FDRs to TDRs. Presence of any number of affected FDRs or SDRs significantly increased risk for BC over population risk; and more than four TDRs, even with no affected FDRs or SDRs, significantly increased risk over population risk. Risk prediction derived from the specific and extended family history constellation of affected relatives allows identification of females at increased risk even when they do not have a conventionally defined high-risk family; these risks could be a powerful, efficient tool to individualize cancer screening and prevention.
Entities:
Keywords:
Breast cancer; Family history; Individualized risk; Relative risk; UPDB
Authors: Marie T Kumerow; Juan L Rodriguez; Shifan Dai; Katherine Kolor; Melissa Rotunno; Lucy A Peipins Journal: Prev Med Date: 2022-04-20 Impact factor: 4.637