PLoS ONE (Jan 2013)

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
https://doi.org/10.1371/journal.pone.0072311
Journal volume & issue
Vol. 8, no. 9
p. e72311

Abstract

Read online

We developed an absolute risk model to identify individuals in the general population at elevated risk of pancreatic cancer.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.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/m(2)) (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.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.