Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

被引：257

作者：

Wolpin, Brian M. ^{[1
,2
]}

Rizzato, Cosmeri ^{[3
]}

Kraft, Peter ^{[4
,5
]}

Kooperberg, Charles ^{[6
]}

Petersen, Gloria M. ^{[7
]}

Wang, Zhaoming ^{[8
,9
]}

Arslan, Alan A. ^{[10
,11
,12
]}

Beane-Freeman, Laura ^{[8
]}

Bracci, Paige M. ^{[13
]}

Buring, Julie ^{[14
,15
]}

Canzian, Federico ^{[3
]}

Duell, Eric J. ^{[16
]}

Gallinger, Steven ^{[17
]}

Giles, Graham G. ^{[18
,19
]}

Goodman, Gary E. ^{[6
]}

Goodman, Phyllis J. ^{[20
]}

Jacobs, Eric J. ^{[21
]}

Kamineni, Aruna ^{[22
]}

Klein, Alison P. ^{[23
,24
]}

Kolonel, Laurence N. ^{[25
]}

Kulke, Matthew H.

Li, Donghui ^{[26
]}

Malats, Nuria ^{[27
]}

Olson, Sara H. ^{[28
]}

Risch, Harvey A. ^{[29
]}

Sesso, Howard D. ^{[4
,14
,15
]}

Visvanathan, Kala ^{[30
]}

White, Emily ^{[31
,32
]}

Zheng, Wei ^{[33
,34
]}

Abnet, Christian C. ^{[8
]}

Albanes, Demetrius ^{[8
]}

Andreotti, Gabriella ^{[8
]}

Austin, Melissa A. ^{[32
]}

Barfield, Richard ^{[5
]}

Basso, Daniela ^{[35
]}

Berndt, Sonja I. ^{[8
]}

Boutron-Ruault, Marie-Christine ^{[36
,37
,38
]}

Brotzman, Michelle ^{[39
]}

Buechler, Markus W. ^{[40
]}

Bueno-de-Mesquita, H. Bas ^{[41
,42
,43
]}

Bugert, Peter ^{[44
]}

Burdette, Laurie ^{[9
]}

Campa, Daniele ^{[45
]}

Caporaso, Neil E. ^{[8
]}

Capurso, Gabriele ^{[46
]}

Chung, Charles ^{[8
,9
]}

Cotterchio, Michelle ^{[47
,48
]}

Costello, Eithne ^{[49
]}

Elena, Joanne ^{[50
]}

Funel, Niccola ^{[51
]}

机构：

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

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

[3] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany

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

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

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

[7] Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN USA

[8] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

[9] Leidos Biomed Res Inc, Div Canc Epidemiol & Genet, Frederick Natl Lab Canc Res, Canc Genom Res Lab,Natl Canc Inst, Frederick, MD USA

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

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

[12] NYU, New York, NY USA

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

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

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

[16] Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol ICO, Canc Epidemiol Res Program, Unit Nutr Environm & Canc, Barcelona, Spain

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

[18] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia

[19] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia

[20] Fred Hutchinson Canc Res Ctr, Southwest Oncol Grp Stat Ctr, Seattle, WA 98104 USA

[21] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA

[22] Grp Hlth Res Inst, Seattle, WA USA

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

[24] Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA

[25] Canc Res Ctr Hawaii, Honolulu, HI USA

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

[27] CNIO Spanish Natl Canc Res Ctr, Genet & Mol Epidemiol Grp, Madrid, Spain

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

[29] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA

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

[31] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA

[32] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[33] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA

[34] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN USA

[35] Univ Hosp Padova, Dept Lab Med, Padua, Italy

[36] INSERM, Ctr Res Epidemiol & Populat Hlth CESP, Nutr Hormones & Womens Hlth Team, Villejuif, France

[37] Univ Paris 11, UMRS 1018, Villejuif, France

[38] IGR, Villejuif, France

[39] Westat Corp, Rockville, MD USA

[40] Univ Heidelberg Hosp, Dept Gen Surg, Heidelberg, Germany

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

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

[43] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

[44] Heidelberg Univ, Med Fac Mannheim, Inst Transfus Med & Immunol, German Red Cross Blood Serv Baden Wurttemberg Hes, Mannheim, Germany

[45] DKFZ, Div Canc Epidemiol, Heidelberg, Germany

[46] Univ Roma La Sapienza, Digest & Liver Dis Unit, I-00185 Rome, Italy

[47] Univ Toronto, Canc Care Ontario, Toronto, ON M5S 1A1, Canada

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

[49] Univ Liverpool, Liverpool Pancreas Biomed Res Unit, Natl Inst Hlth, Liverpool L69 3BX, Merseyside, England

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

来源：

NATURE GENETICS | 2014年 / 46卷 / 09期

基金：

美国国家卫生研究院;

关键词：

BLADDER-CANCER; RISK LOCI; LINKAGE DISEQUILIBRIUM; GENETIC SUSCEPTIBILITY; VARIANTS; METAANALYSIS; IMPUTATION; PROSTATE; SURVIVAL; BREAST;

D O I：

10.1038/ng.3052

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 x 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 x 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 x 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 x 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 x 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 x 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.

引用

页码：994 / +

页数：9

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