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

被引：111

作者：

Klein, Alison P. ^{[1
,2
,3
]}

Lindstroem, Sara ^{[4
,5
]}

Mendelsohn, Julie B. ^{[6
]}

Steplowski, Emily ^{[7
]}

Arslan, Alan A. ^{[8
,9
,10
]}

Bueno-de-Mesquita, H. Bas ^{[11
,12
]}

Fuchs, Charles S. ^{[13
,14
,15
]}

Gallinger, Steven ^{[16
]}

Gross, Myron ^{[17
]}

Helzlsouer, Kathy ^{[18
,19
,20
]}

Holly, Elizabeth A. ^{[21
]}

Jacobs, Eric J. ^{[22
]}

LaCroix, Andrea ^{[23
]}

Li, Donghui ^{[24
]}

Mandelson, Margaret T. ^{[23
,25
]}

Olson, Sara H. ^{[26
]}

Petersen, Gloria M. ^{[27
]}

Risch, Harvey A. ^{[28
]}

Stolzenberg-Solomon, Rachael Z. ^{[6
]}

Zheng, Wei ^{[29
,30
]}

Amundadottir, Laufey ^{[6
]}

Albanes, Demetrius ^{[6
]}

Allen, Naomi E. ^{[31
,32
]}

Bamlet, William R. ^{[27
]}

Boutron-Ruault, Marie-Christine ^{[33
,34
]}

Buring, Julie E. ^{[35
,36
,37
,38
]}

Bracci, Paige M. ^{[21
]}

Canzian, Federico ^{[39
]}

Clipp, Sandra ^{[40
]}

Cotterchio, Michelle ^{[41
,42
]}

Duell, Eric J. ^{[43
]}

Elena, Joanne ^{[44
]}

Gaziano, J. Michael ^{[35
,36
,37
,45
]}

Giovannucci, Edward L. ^{[4
,14
,15
,46
]}

Goggins, Michael ^{[47
,48
,49
]}

Hallmans, Goeran ^{[50
]}

Hassan, Manal ^{[24
]}

Hutchinson, Amy ^{[51
]}

Hunter, David J. ^{[4
,46
]}

Kooperberg, Charles ^{[52
]}

Kurtz, Robert C. ^{[53
]}

Liu, Simin ^{[54
,55
,56
]}

Overvad, Kim ^{[57
]}

Palli, Domenico ^{[58
]}

Patel, Alpa V. ^{[22
]}

Rabe, Kari G. ^{[27
]}

Shu, Xiao-Ou ^{[29
,30
]}

Slimani, Nadia ^{[59
]}

Tobias, Geoffrey S. ^{[6
]}

Trichopoulos, Dimitrios ^{[4
,60
]}

机构：

[1] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD 21218 USA

[2] Johns Hopkins Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD USA

[3] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA

[4] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[5] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA

[6] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA

[7] Informat Management Serv Inc, Silver Spring, MD USA

[8] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA

[9] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA

[10] NYU, Inst Canc, New York, NY USA

[11] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands

[12] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands

[13] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[14] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA

[15] Harvard Univ, Sch Med, Boston, MA USA

[16] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[17] Univ Minnesota, Sch Med, Dept Lab Med Pathol, Minneapolis, MN 55455 USA

[18] Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA

[19] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA

[20] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA

[21] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

[22] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA

[23] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA

[24] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA

[25] Grp Hlth Ctr Hlth Studies, Seattle, WA USA

[26] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA

[27] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA

[28] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Sch Publ Hlth, New Haven, CT 06510 USA

[29] Vanderbilt Univ, Dept Med, Nashville, TN USA

[30] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37235 USA

[31] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England

[32] UK Biobank, Oxford, England

[33] INSERM, Villejuif, France

[34] Inst Gustave Roussy, Villejuif, France

[35] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA

[36] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA

[37] Harvard Univ, Sch Med, Boston, MA USA

[38] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA

[39] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany

[40] George W Comstock Ctr Publ Hlth Res & Prevent, Hagerstown, MD USA

[41] Canc Care Ontario, Toronto, ON, Canada

[42] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada

[43] Catalan Inst Oncol ICO IDIBELL, Unit Nutr Environm & Canc, Barcelona, Spain

[44] NCI, Div Canc Control & Populat Sci, NIH, US Dept HHS, Bethesda, MD 20892 USA

[45] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA

[46] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[47] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

[48] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

[49] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[50] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden

来源：

PLOS ONE | 2013年 / 8卷 / 09期

关键词：

COHORT-CONSORTIUM PANSCAN; GENOME-WIDE ASSOCIATION; ABO BLOOD-GROUP; POOLED-ANALYSIS; FAMILY-HISTORY; HEREDITARY PANCREATITIS; GENETIC EPIDEMIOLOGY; SUSCEPTIBILITY; METAANALYSIS; MUTATIONS;

D O I：

10.1371/journal.pone.0072311

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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/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. 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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