An Absolute Risk Model to Identify Individuals at Elevated Risk for Pancreatic Cancer in the General Population

PLOS ONE, Dec 2019

Purpose We developed an absolute risk model to identify individuals in the general population at elevated risk of pancreatic cancer. Patients and Methods Using data on 3,349 cases and 3,654 controls from the PanScan Consortium, we developed a relative risk model for men and women of European ancestry based on non-genetic and genetic risk factors for pancreatic cancer. We estimated absolute risks based on these relative risks and population incidence rates. Results Our risk model included current smoking (multivariable adjusted odds ratio (OR) and 95% confidence interval: 2.20 [1.84–2.62]), heavy alcohol use (>3 drinks/day) (OR: 1.45 [1.19–1.76]), obesity (body mass index >30 kg/m2) (OR: 1.26 [1.09–1.45]), diabetes >3 years (nested case-control OR: 1.57 [1.13–2.18], case-control OR: 1.80 [1.40–2.32]), family history of pancreatic cancer (OR: 1.60 [1.20–2.12]), non-O ABO genotype (AO vs. OO genotype) (OR: 1.23 [1.10–1.37]) to (BB vs. OO genotype) (OR 1.58 [0.97–2.59]), rs3790844(chr1q32.1) (OR: 1.29 [1.19–1.40]), rs401681(5p15.33) (OR: 1.18 [1.10–1.26]) and rs9543325(13q22.1) (OR: 1.27 [1.18–1.36]). The areas under the ROC curve for risk models including only non-genetic factors, only genetic factors, and both non-genetic and genetic factors were 58%, 57% and 61%, respectively. We estimate that fewer than 3/1,000 U.S. non-Hispanic whites have more than a 5% predicted lifetime absolute risk. Conclusion Although absolute risk modeling using established risk factors may help to identify a group of individuals at higher than average risk of pancreatic cancer, the immediate clinical utility of our model is limited. However, a risk model can increase awareness of the various risk factors for pancreatic cancer, including modifiable behaviors.

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An Absolute Risk Model to Identify Individuals at Elevated Risk for Pancreatic Cancer in the General Population

doi:10.1371/journal.pone.0072311.t002 An Absolute Risk Model to Identify Individuals at Elevated Risk for Pancreatic Cancer in the General Population Alison P. Klein Sara Lindstro m Julie B. Mendelsohn Emily Steplowski Alan A. Arslan H. Bas Bueno-de-Mesquita Charles S. Fuchs Steven Gallinger Myron Gross Kathy Helzlsouer Elizabeth A. Holly Eric J. Jacobs Andrea LaCroix Donghui Li Margaret T. Mandelson Sara H. Olson Gloria M. Petersen Harvey A. Risch Rachael Z. Stolzenberg-Solomon Wei Zheng Laufey Amundadottir Demetrius Albanes Naomi E. Allen William R. Bamlet Marie-Christine Boutron-Ruault Julie E. Buring Paige M. Bracci Federico Canzian Sandra Clipp Michelle Cotterchio Eric J. Duell Joanne Elena J. Michael Gaziano Edward L. Giovannucci Michael Goggins Go ran Hallmans Manal Hassan Amy Hutchinson David J. Hunter Charles Kooperberg Robert C. Kurtz Simin Liu Kim Overvad Domenico Palli Alpa V. Patel Kari G. Rabe Xiao- Ou Shu Nadia Slimani Geoffrey S. Tobias Dimitrios Trichopoulos Stephen K. Van Den Eeden Paolo Vineis Jarmo Virtamo Jean Wactawski-Wende Brian M. Wolpin Herbert Yu Kai Yu Anne Zeleniuch-Jacquotte Stephen J. Chanock Robert N. Hoover Patricia Hartge Peter Kraft - Purpose: We developed an absolute risk model to identify individuals in the general population at elevated risk of pancreatic cancer. Patients and Methods: Using data on 3,349 cases and 3,654 controls from the PanScan Consortium, we developed a relative risk model for men and women of European ancestry based on non-genetic and genetic risk factors for pancreatic cancer. We estimated absolute risks based on these relative risks and population incidence rates. Results: Our risk model included current smoking (multivariable adjusted odds ratio (OR) and 95% confidence interval: 2.20 [1.842.62]), heavy alcohol use (.3 drinks/day) (OR: 1.45 [1.191.76]), obesity (body mass index .30 kg/m2) (OR: 1.26 [1.09 1.45]), diabetes .3 years (nested case-control OR: 1.57 [1.132.18], case-control OR: 1.80 [1.402.32]), family history of pancreatic cancer (OR: 1.60 [1.202.12]), non-O ABO genotype (AO vs. OO genotype) (OR: 1.23 [1.101.37]) to (BB vs. OO genotype) (OR 1.58 [0.972.59]), rs3790844(chr1q32.1) (OR: 1.29 [1.191.40]), rs401681(5p15.33) (OR: 1.18 [1.101.26]) and rs9543325(13q22.1) (OR: 1.27 [1.181.36]). The areas under the ROC curve for risk models including only non-genetic factors, only genetic factors, and both non-genetic and genetic factors were 58%, 57% and 61%, respectively. We estimate that fewer than 3/1,000 U.S. non-Hispanic whites have more than a 5% predicted lifetime absolute risk. Conclusion: Although absolute risk modeling using established risk factors may help to identify a group of individuals at higher than average risk of pancreatic cancer, the immediate clinical utility of our model is limited. However, a risk model can increase awareness of the various risk factors for pancreatic cancer, including modifiable behaviors. Citation: Klein AP, Lindstro m S, Mendelsohn JB, Steplowski E, Arslan AA, et al. (2013) An Absolute Risk Model to Identify Individuals at Elevated Risk for Pancreatic Cancer in the General Population. PLoS ONE 8(9): e72311. doi:10.1371/journal.pone.0072311 Editor: Francisco X. Real, Centro Nacional de Investigaciones Oncolo gicas (CNIO), Spain Received November 7, 2012; Accepted July 10, 2013; Published September 13, 2013 This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Funding: The NYU Womens Health Study is supported by research grants R01CA034588, R01CA098661, center grant P30CA016087 from the NCI and the center grant ES000260 from the National Institute of Environmental Health Sciences. The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. The Mayo Clinic Molecular Epidemiology of Pancreatic Cancer study is supported by the Mayo Clinic SPORE in Pancreatic Cancer (P50 CA102701). The authors would like to acknowledge Traci Hammer, Jodi Cogswell, Hugues Sicotte, Ann Oberg, Janet Olson, Martha Matsumoto, and Dennis Robinson. The Yale University study was supported by grant number 5R01CA098870 from the NCI, NIH. The cooperation of 30 Connecticut hospitals, including Stamford Hospital, in allowing patient access, is gratefully acknowledged. This study was approved by the State of Connecticut Department of Public Health Human Investigation Committee. Certain data used in this study were obtained from the Connecticut Tumor Registry in the Connecticut Department of Public Health. The authors assume full responsibility for analyses and interpretation of these data. The PHS, NHS, HPFS and WHS at Harvard were supported by the NCI, NIH (Grants No. (...truncated)


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Alison P. Klein, Sara Lindström, Julie B. Mendelsohn, Emily Steplowski, Alan A. Arslan, H. Bas Bueno-de-Mesquita, Charles S. Fuchs, Steven Gallinger, Myron Gross, Kathy Helzlsouer, Elizabeth A. Holly, Eric J. Jacobs, Andrea LaCroix, Donghui Li, Margaret T. Mandelson, Sara H. Olson, Gloria M. Petersen, Harvey A. Risch, Rachael Z. Stolzenberg-Solomon, Wei Zheng, Laufey Amundadottir, Demetrius Albanes, Naomi E. Allen, William R. Bamlet, Marie-Christine Boutron-Ruault, Julie E. Buring, Paige M. Bracci, Federico Canzian, Sandra Clipp, Michelle Cotterchio, Eric J. Duell, Joanne Elena, J. Michael Gaziano, Edward L. Giovannucci, Michael Goggins, Göran Hallmans, Manal Hassan, Amy Hutchinson, David J. Hunter, Charles Kooperberg, Robert C. Kurtz, Simin Liu, Kim Overvad, Domenico Palli, Alpa V. Patel, Kari G. Rabe, Xiao-Ou Shu, Nadia Slimani, Geoffrey S. Tobias, Dimitrios Trichopoulos, Stephen K. Van Den Eeden, Paolo Vineis, Jarmo Virtamo, Jean Wactawski-Wende, Brian M. Wolpin, Herbert Yu, Kai Yu, Anne Zeleniuch-Jacquotte, Stephen J. Chanock, Robert N. Hoover, Patricia Hartge, Peter Kraft. An Absolute Risk Model to Identify Individuals at Elevated Risk for Pancreatic Cancer in the General Population, PLOS ONE, 2013, Volume 8, Issue 9, DOI: 10.1371/journal.pone.0072311