A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33

被引：497

作者：

Petersen, Gloria M. ^{[2
]}

Amundadottir, Laufey ^{[1
]}

Fuchs, Charles S. ^{[3
,4
]}

Kraft, Peter ^{[6
]}

Stolzenberg-Solomon, Rachael Z.

Jacobs, Kevin B. ^{[7
,8
]}

Arslan, Alan A. ^{[9
,10
,11
]}

Bueno-de-Mesquita, H. Bas ^{[12
,13
]}

Gallinger, Steven ^{[14
]}

Gross, Myron ^{[15
]}

Helzlsouer, Kathy ^{[16
]}

Holly, Elizabeth A. ^{[17
]}

Jacobs, Eric J. ^{[18
]}

Klein, Alison P. ^{[19
,20
]}

LaCroix, Andrea ^{[21
]}

Li, Donghui ^{[22
]}

Mandelson, Margaret T. ^{[21
,23
]}

Olson, Sara H. ^{[24
]}

Risch, Harvey A. ^{[25
]}

Zheng, Wei ^{[26
,27
]}

Albanes, Demetrius

Bamlet, William R. ^{[2
]}

Berg, Christine D. ^{[28
]}

Boutron-Ruault, Marie-Christine ^{[29
]}

Buring, Julie E. ^{[30
,31
,32
]}

Bracci, Paige M. ^{[17
]}

Canzian, Federico ^{[33
]}

Clipp, Sandra ^{[34
]}

Cotterchio, Michelle ^{[35
]}

de Andrade, Mariza ^{[2
]}

Duell, Eric J. ^{[36
]}

Gaziano, J. Michael ^{[37
,38
,39
,40
]}

Giovannucci, Edward L. ^{[4
,5
,41
]}

Goggins, Michael ^{[42
,43
,44
]}

Hallmans, Goran ^{[45
]}

Hankinson, Susan E. ^{[4
,5
]}

Hassan, Manal ^{[22
]}

Howard, Barbara ^{[46
]}

Hunter, David J. ^{[4
,5
]}

Hutchinson, Amy ^{[7
]}

Jenab, Mazda

Kaaks, Rudolf

Kooperberg, Charles ^{[21
]}

Krogh, Vittorio ^{[47
]}

Kurtz, Robert C. ^{[48
]}

Lynch, Shannon M. ^{[49
]}

McWilliams, Robert R. ^{[2
]}

Mendelsohn, Julie B.

Michaud, Dominique S. ^{[5
,50
]}

Parikh, Hemang ^{[1
]}

机构：

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

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

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

[4] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA

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

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

[7] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA

[8] Bioinformed Consulting Serv, Gaithersburg, MD USA

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[25] Yale Univ, Sch Publ Hlth, New Haven, CT USA

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

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

[28] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA

[29] Univ Paris Sud, INSERM, Inst Gustave Roussy, Villejuif, France

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

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

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

[33] German Canc Res Ctr, Heidelberg, Germany

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

[35] Univ Toronto, Canc Care Ontario & Dalla Lana Sch Publ Hlth, Toronto, ON, Canada

[36] Catalan Inst Oncol, Barcelona, Spain

[37] Brigham & Womens Hosp, Phys Hlth Study, Div Aging, Dept Med, Boston, MA 02115 USA

[38] Brigham & Womens Hosp, Phys Hlth Study, Div Cardiovasc Dis, Dept Med, Boston, MA 02115 USA

[39] Brigham & Womens Hosp, Phys Hlth Study, Div Prevent Med, Dept Med, Boston, MA 02115 USA

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

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

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

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

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

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

[46] Georgetown Univ, MedStar Res Inst, Hyattsville, MD USA

[47] Fdn IRCCS, Ist Nazl Tumoridi Milano, Nutr Epidemiol Unit, Milan, Italy

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

[49] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA

[50] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England

来源：

NATURE GENETICS | 2010年 / 42卷 / 03期

关键词：

BASE-LINE CHARACTERISTICS; RECOMBINATION HOTSPOTS; WOMENS HEALTH; BREAST-CANCER; RISK; GENE; VARIANTS; TELOMERASE; CELLS; LUNG;

D O I：

10.1038/ng.522

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 x 10(-11), per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 x 10(-8), per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 x 10(-10), per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 x 10(-7), per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.

引用

页码：224 / U29

页数：7

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