Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer

被引：548

作者：

Amundadottir, Laufey ^{[1
,2
]}

Kraft, Peter ^{[3
,4
]}

Stolzenberg-Solomon, Rachael Z. ^{[2
]}

Fuchs, Charles S. ^{[5
,6
]}

Petersen, Gloria M. ^{[7
]}

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

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

Gross, Myron ^{[13
]}

Helzlsouer, Kathy ^{[14
]}

Jacobs, Eric J. ^{[15
]}

LaCroix, Andrea ^{[16
]}

Zheng, Wei ^{[17
,18
]}

Albanes, Demetrius ^{[2
]}

Bamlet, William ^{[7
]}

Berg, Christine D. ^{[19
]}

Berrino, Franco ^{[20
]}

Bingham, Sheila ^{[21
]}

Buring, Julie E. ^{[22
,23
,24
]}

Bracci, Paige M. ^{[25
]}

Canzian, Federico ^{[26
]}

Clavel-Chapelon, Francoise ^{[27
,28
]}

Clipp, Sandra ^{[29
]}

Cotterchio, Michelle ^{[30
]}

de Andrade, Mariza ^{[7
]}

Duell, Eric J. ^{[31
]}

Fox, John W., Jr. ^{[32
]}

Gallinger, Steven ^{[33
]}

Gaziano, J. Michael ^{[34
,35
]}

Giovannucci, Edward L. ^{[3
,6
,36
]}

Goggins, Michael ^{[37
,38
,39
]}

Gonzalez, Carlos A. ^{[40
]}

Hallmans, Goran ^{[41
]}

Hankinson, Susan E. ^{[3
,6
]}

Hassan, Manal ^{[42
]}

Holly, Elizabeth A. ^{[25
]}

Hunter, David J. ^{[3
,6
]}

Hutchinson, Amy ^{[2
,43
]}

Jackson, Rebecca ^{[44
,45
]}

Jacobs, Kevin B. ^{[43
,46
]}

Jenab, Mazda ^{[31
]}

Kaaks, Rudolf ^{[26
]}

Klein, Alison P. ^{[47
]}

Kooperberg, Charles ^{[16
]}

Kurtz, Robert C. ^{[49
]}

Li, Donghui ^{[42
]}

Lynch, Shannon M. ^{[48
]}

Mandelson, Margaret ^{[16
,50
]}

McWilliams, Robert R. ^{[51
]}

Mendelsohn, Julie B. ^{[2
]}

Michaud, Dominique S. ^{[3
,52
]}

机构：

[1] Natl Canc Inst, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlt & Human Serv, Bethesda, MD 20892 USA

[2] Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD USA

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

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

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

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

[7] Mayo Clin, Dept Hlth Sci Res, Coll Med, Rochester, MN USA

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

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

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

[11] Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands

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

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

[14] St Johns Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA

[15] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA

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

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

[18] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA

[19] Natl Canc Inst, Canc Prevent Div, NIH, Dept Hlth & Human Serv, Bethesda, MD USA

[20] Ist Nazl Tumori, Etiol Epidemiol & Prevent Unit, Fdn IRCCS, I-20133 Milan, Italy

[21] Univ Cambridge, MRC, Dunn Human Nutr Unit, Cambridge, England

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

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

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

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

[26] German Canc Res Ctr, Div Canc Epidemiol, DKFZ, D-6900 Heidelberg, Germany

[27] INSERM, Villejuif, France

[28] Inst Gustave Roussy, Villejuif, France

[29] Johns Hopkins Bloomberg Sch Publ Hlth, George W Comstock Ctr Publ Hlth Res & Prevent, Hagerstown, MD USA

[30] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada

[31] Int Agcy Res Canc, F-69372 Lyon, France

[32] Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA

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

[34] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA

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

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

[37] Johns Hopkins Univ, Sch Med, Dept Oncol, Sol Goldman Pancreat Res Ctr, Baltimore, MD 21205 USA

[38] Johns Hopkins Univ, Sch Med, Dept Pathol, Sol Goldman Pancreat Res Ctr, Baltimore, MD 21205 USA

[39] Johns Hopkins Univ, Sch Med, Dept Med, Sol Goldman Pancreat Res Ctr, Baltimore, MD 21205 USA

[40] ICO, Unit Nutr Environm & Canc, Canc Epidemiol Res Programme, Barcelona, Spain

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

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

[43] SAIC Frederick Inc, Core Genotyping Facil, Adv Technol Program, NCI, Frederick, MD USA

[44] Ohio State Univ, Dept Internal Med, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA

[45] Ohio State Univ, Ctr Clin & Translat Sci, Columbus, OH 43210 USA

[46] Bioinformed LLC, Gaithersburg, MD USA

[47] Johns Hopkins Med Inst, Dept Epidemiol, Johns Hopkins Bloomberg Sch Publ Hlth, Sol Goldman Pancreat Res Ctr, Baltimore, MD 21205 USA

[48] Natl Canc Inst, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, NIH,Dept Hlth & Human Serv, Bethesda, MD USA

[49] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA

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

来源：

NATURE GENETICS | 2009年 / 41卷 / 09期

关键词：

BASE-LINE CHARACTERISTICS; WOMENS HEALTH; BLOOD-GROUP; RISK; DESIGN; GENES; POLYMORPHISMS; RATIONALE; MORTALITY; ALLERGIES;

D O I：

10.1038/ng.429

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.

引用

页码：986 / U47

页数：7

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