Pancreatic cancer risk to siblings of probands in bilineal cancer settings |
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| Authors: | Kari G. Rabe Maria A. Stevens Amanda Toledo Hernández Shruti Chandra Joleen M. Hubbard Jennifer L. Kemppainen Shounak Majumder Gloria M. Petersen |
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| Affiliation: | 1. Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN;2. Division of Health Care Policy and Research, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN;3. School of Medicine, Medical Science Campus, University of Puerto Rico, San Juan, Puerto Rico;4. Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN;5. Department of Medical Oncology, Mayo Clinic, Rochester, MN;6. Department of Clinical Genomics, Mayo Clinic, Rochester, MN;7. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN;1. Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;2. MRC Unit for Genomic and Precision Medicine, Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;3. Department of Biochemistry and Medical Microbiology, School of Medicine, University of Namibia, Windhoek, Namibia;4. Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;5. Division of Human Genetics, Department of Pathology, Colorectal Cancer Research Group, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa;1. Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, Milan, Italy;2. Pediatric Radiology and Neuroradiology Department, Vittore Buzzi Children’s Hospital, Milan, Italy;3. COALA (Center for diagnosis and treatment of leukodystrophies), Vittore Buzzi Children''s Hospital, Milan, Italy;4. Child Neuropsychiatry Unit, UONPIA ASST Rhodense, Milan, Italy;5. Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, University of Milan, Milan, Italy;6. Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, Vrije Universiteit Amsterdam, University of Amsterdam, Amsterdam, The Netherlands;7. Molecular Genetics Section, Medical Genetics Laboratory, Papa Giovanni XXIII Hospital, Bergamo, Italy;8. Child Neurology Unit, Vittore Buzzi Children''s Hospital, Milan, Italy;1. School of Women’s and Children’s Health, University of New South Wales, Randwick, New South Wales, Australia;2. Centre for Clinical Genetics, Sydney Children’s Hospital, Randwick, New South Wales, Australia;3. Sydney Health Ethics, Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, New South Wales, Australia;4. Victorian Clinical Genetics Services, Parkville, Victoria, Australia;5. Murdoch Children’s Research Institute, Parkville, Victoria, Australia;6. UWA Centre for Medical Research, University of Western Australia, Nedlands, Western Australia, Australia;7. Harry Perkins Institute of Medical Research, Nedlands, Western Australia, Australia;8. NSW Health Pathology East Genomics Laboratory, Randwick, New South Wales, Australia;1. Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo, Norway;2. Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, United Kingdom;3. Applied Tumor Genomic Research Program, University of Helsinki, Helsinki, Finland;1. Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL;2. Departments of Pathology and Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA;3. Center for Medical Genetics and Genomics, UPMC Magee-Womens Hospital, Pittsburgh, PA;4. Department of Obstetrics & Gynecology and Women’s Health, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY;5. Department of Obstetrics and Gynecology, Prisma Health, Columbia, SC;1. Vanderbilt University School of Medicine, Medical Scientist Training Program, Vanderbilt University, Nashville, TN;2. Vanderbilt Center for Arrhythmia Research and Therapeutics (VanCART), Vanderbilt University Medical Center, Nashville, TN;3. Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN;4. Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN;5. Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN |
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| Abstract: | PurposePancreatic cancer (PC) risk is increased in families, but PC risk and risk perception have been understudied when both parents have cancer.MethodsAn unbiased method defining cancer triads (proband with PC and both parents with cancer) in a prospective registry estimated risk of PC to probands’ siblings in triad group 1 (no parent with PC), group 2 (1 parent with PC), and group 3 (both parents with PC). We estimated standardized incidence ratios (SIRs) using a Surveillance, Epidemiology, and End Results (SEER) reference. We also estimated the risk when triad probands carried germline pathogenic/likely pathogenic variants in any of the 6 PC-associated genes (ATM, BRCA1, BRCA2, CDKN2A, MLH1, and TP53). PC risk perception/concern was surveyed in siblings and controls.ResultsRisk of PC was higher (SIR = 3.5; 95% CI = 2.2-5.2) in 933 at-risk siblings from 297 triads. Risk increased by triad group: 2.8 (95% CI = 1.5-4.5); 4.5 (95% CI = 1.6-9.7); and 21.2 (95% CI = 4.3-62.0). SIR in variant-negative triads was 3.0 (95% CI = 1.6-5.0), whereas SIR in variant-positive triads was 10.0 (95% CI = 3.2-23.4). Siblings’ perceived risk/concern of developing PC increased by triad group.ConclusionSibling risks were 2.8- to 21.2-fold higher than that of the general population. Positive variant status increased the risk in triads. Increasing number of PC cases in a triad was associated with increased concern and perceived PC risk. |
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| Keywords: | Familial risk Pancreatic cancer Risk perception |
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