An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population.
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 M-C., 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 X-O., 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.
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.