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

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

doi:10.1371/journal.pone.0072311

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

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 ZhengLaufey 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

Quantitative Health Sciences

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English (US)
Article number	e72311
Journal	PloS one
Volume	8
Issue number	9
DOIs	https://doi.org/10.1371/journal.pone.0072311
State	Published - Sep 13 2013

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Klein, A. P., Lindström, S., Mendelsohn, J. B., Steplowski, E., Arslan, A. A., Bueno-de-Mesquita, H. B., Fuchs, C. S., Gallinger, S., Gross, M., Helzlsouer, K., Holly, E. A., Jacobs, E. J., LaCroix, A., Li, D., Mandelson, M. T., Olson, S. H., Petersen, G. M., Risch, H. A., Stolzenberg-Solomon, R. Z., ... Kraft, P. (2013). An Absolute Risk Model to Identify Individuals at Elevated Risk for Pancreatic Cancer in the General Population. PloS one, 8(9), Article e72311. https://doi.org/10.1371/journal.pone.0072311

Klein, AP, Lindström, S, Mendelsohn, JB, Steplowski, E, Arslan, AA, Bueno-de-Mesquita, HB, Fuchs, CS, Gallinger, S, Gross, M, Helzlsouer, K, Holly, EA, Jacobs, EJ, LaCroix, A, Li, D, Mandelson, MT, Olson, SH, Petersen, GM, Risch, HA, Stolzenberg-Solomon, RZ, Zheng, W, Amundadottir, L, Albanes, D, Allen, NE, Bamlet, WR, Boutron-Ruault, MC, Buring, JE, Bracci, PM, Canzian, F, Clipp, S, Cotterchio, M, Duell, EJ, Elena, J, Gaziano, JM, Giovannucci, EL, Goggins, M, Hallmans, G, Hassan, M, Hutchinson, A, Hunter, DJ, Kooperberg, C, Kurtz, RC, Liu, S, Overvad, K, Palli, D, Patel, AV, Rabe, KG, Shu, XO, Slimani, N, Tobias, GS, Trichopoulos, D, Van Den Eeden, SK, Vineis, P, Virtamo, J, Wactawski-Wende, J, Wolpin, BM, Yu, H, Yu, K, Zeleniuch-Jacquotte, A, Chanock, SJ, Hoover, RN, Hartge, P & Kraft, P 2013, 'An Absolute Risk Model to Identify Individuals at Elevated Risk for Pancreatic Cancer in the General Population', PloS one, vol. 8, no. 9, e72311. https://doi.org/10.1371/journal.pone.0072311

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

abstract = "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.",

author = "Klein, {Alison P.} and Sara Lindstr{\"o}m and Mendelsohn, {Julie B.} and Emily Steplowski and Arslan, {Alan A.} and Bueno-de-Mesquita, {H. Bas} and Fuchs, {Charles S.} and Steven Gallinger and Myron Gross and Kathy Helzlsouer and Holly, {Elizabeth A.} and Jacobs, {Eric J.} and Andrea LaCroix and Donghui Li and Mandelson, {Margaret T.} and Olson, {Sara H.} and Petersen, {Gloria M.} and Risch, {Harvey A.} and Stolzenberg-Solomon, {Rachael Z.} and Wei Zheng and Laufey Amundadottir and Demetrius Albanes and Allen, {Naomi E.} and Bamlet, {William R.} and Boutron-Ruault, {Marie Christine} and Buring, {Julie E.} and Bracci, {Paige M.} and Federico Canzian and Sandra Clipp and Michelle Cotterchio and Duell, {Eric J.} and Joanne Elena and Gaziano, {J. Michael} and Giovannucci, {Edward L.} and Michael Goggins and G{\"o}ran Hallmans and Manal Hassan and Amy Hutchinson and Hunter, {David J.} and Charles Kooperberg and Kurtz, {Robert C.} and Simin Liu and Kim Overvad and Domenico Palli and Patel, {Alpa V.} and Rabe, {Kari G.} and Shu, {Xiao Ou} and Nadia Slimani and Tobias, {Geoffrey S.} and Dimitrios Trichopoulos and {Van Den Eeden}, {Stephen K.} and Paolo Vineis and Jarmo Virtamo and Jean Wactawski-Wende and Wolpin, {Brian M.} and Herbert Yu and Kai Yu and Anne Zeleniuch-Jacquotte and Chanock, {Stephen J.} and Hoover, {Robert N.} and Patricia Hartge and Peter Kraft",

year = "2013",

month = sep,

day = "13",

doi = "10.1371/journal.pone.0072311",

language = "English (US)",

volume = "8",

journal = "PloS one",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "9",

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TY - JOUR

T1 - An Absolute Risk Model to Identify Individuals at Elevated Risk for Pancreatic Cancer in the General Population

AU - Klein, Alison P.

AU - Lindström, Sara

AU - Mendelsohn, Julie B.

AU - Steplowski, Emily

AU - Arslan, Alan A.

AU - Bueno-de-Mesquita, H. Bas

AU - Fuchs, Charles S.

AU - Gallinger, Steven

AU - Gross, Myron

AU - Helzlsouer, Kathy

AU - Holly, Elizabeth A.

AU - Jacobs, Eric J.

AU - LaCroix, Andrea

AU - Li, Donghui

AU - Mandelson, Margaret T.

AU - Olson, Sara H.

AU - Petersen, Gloria M.

AU - Risch, Harvey A.

AU - Stolzenberg-Solomon, Rachael Z.

AU - Zheng, Wei

AU - Amundadottir, Laufey

AU - Albanes, Demetrius

AU - Allen, Naomi E.

AU - Bamlet, William R.

AU - Boutron-Ruault, Marie Christine

AU - Buring, Julie E.

AU - Bracci, Paige M.

AU - Canzian, Federico

AU - Clipp, Sandra

AU - Cotterchio, Michelle

AU - Duell, Eric J.

AU - Elena, Joanne

AU - Gaziano, J. Michael

AU - Giovannucci, Edward L.

AU - Goggins, Michael

AU - Hallmans, Göran

AU - Hassan, Manal

AU - Hutchinson, Amy

AU - Hunter, David J.

AU - Kooperberg, Charles

AU - Kurtz, Robert C.

AU - Liu, Simin

AU - Overvad, Kim

AU - Palli, Domenico

AU - Patel, Alpa V.

AU - Rabe, Kari G.

AU - Shu, Xiao Ou

AU - Slimani, Nadia

AU - Tobias, Geoffrey S.

AU - Trichopoulos, Dimitrios

AU - Van Den Eeden, Stephen K.

AU - Vineis, Paolo

AU - Virtamo, Jarmo

AU - Wactawski-Wende, Jean

AU - Wolpin, Brian M.

AU - Yu, Herbert

AU - Yu, Kai

AU - Zeleniuch-Jacquotte, Anne

AU - Chanock, Stephen J.

AU - Hoover, Robert N.

AU - Hartge, Patricia

AU - Kraft, Peter

PY - 2013/9/13

Y1 - 2013/9/13

N2 - 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.

AB - 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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DO - 10.1371/journal.pone.0072311

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VL - 8

JO - PloS one

JF - PloS one

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ER -

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

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