Genome-wide association study of survival in patients with pancreatic adenocarcinoma

被引：49

作者：

Wu, Chen ^{[1
,2
,3
]}

Kraft, Peter ^{[1
,4
,5
]}

Stolzenberg-Solomon, Rachael ^{[6
]}

Steplowski, Emily ^{[7
]}

Brotzman, Michelle ^{[8
]}

Xu, Mousheng ^{[1
]}

Mudgal, Poorva ^{[1
]}

Amundadottir, Laufey ^{[6
]}

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

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

Gross, Myron ^{[14
]}

Helzlsouer, Kathy ^{[15
,16
]}

Jacobs, Eric J. ^{[17
]}

Kooperberg, Charles ^{[18
]}

Petersen, Gloria M. ^{[19
]}

Zheng, Wei ^{[20
,21
]}

Albanes, Demetrius ^{[6
]}

Boutron-Ruault, Marie-Christine ^{[22
,23
]}

Buring, Julie E. ^{[24
,25
,26
]}

Canzian, Federico ^{[27
]}

Cao, Guangwen ^{[28
]}

Duell, Eric J. ^{[29
]}

Elena, Joanne W. ^{[30
]}

Gaziano, J. Michael ^{[24
,25
,31
]}

Giovannucci, Edward L. ^{[1
,32
,33
,34
]}

Hallmans, Goran ^{[35
]}

Hutchinson, Amy ^{[36
]}

Hunter, David J. ^{[1
,32
]}

Jenab, Mazda ^{[37
]}

Jiang, Guoliang ^{[38
]}

Khaw, Kay-Tee ^{[39
]}

LaCroix, Andrea ^{[40
]}

Li, Zhaoshen ^{[41
]}

Mendelsohn, Julie B. ^{[6
]}

Panico, Salvatore ^{[42
]}

Patel, Alpa V. ^{[17
]}

Qian, Zhi Rong ^{[43
]}

Riboli, Elio ^{[44
]}

Sesso, Howard ^{[24
,25
]}

Shen, Hongbing ^{[45
]}

Shu, Xiao-Ou ^{[20
,21
]}

Tjonneland, Anne ^{[46
]}

Tobias, Geoffrey S. ^{[6
]}

Trichopoulos, Dimitrios ^{[1
,47
]}

Virtamo, Jarmo ^{[48
]}

Visvanathan, Kala ^{[49
,50
]}

Wactawski-Wende, Jean ^{[51
]}

Wang, Chengfeng ^{[3
,52
]}

Yu, Kai ^{[6
]}

Zeleniuch-Jacquotte, Anne ^{[10
,11
]}

机构：

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

[2] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100021, Peoples R China

[3] Peking Union Med Coll, Beijing 100021, Peoples R China

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

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

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

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

[8] Westat Corp, Rockville, MD USA

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

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

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

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

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

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

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

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

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

[18] Fred Hutchinson Canc Res Ctr, Div Publ Hlth, Program Biostat & Biomath, Seattle, WA 98104 USA

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

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

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

[22] INSERM, Villejuif, France

[23] Inst Gustave Roussy, Villejuif, France

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

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

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

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

[28] Second Mil Med Univ, Dept Epidemiol, Shanghai, Peoples R China

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

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

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

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

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

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

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

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

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

[38] Fudan Univ, Canc Hosp, Dept Radiat Oncol, Shanghai 200433, Peoples R China

[39] Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Clin Gerontol Unit, Cambridge CB2 2QQ, England

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

[41] Second Mil Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Shanghai, Peoples R China

[42] Univ Naples Federico II, Dept Clin & Expt Med, Naples, Italy

[43] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[44] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England

[45] Nanjing Med Univ, Ctr Canc, Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China

[46] Danish Canc Soc Res Ctr, Copenhagen, Denmark

[47] Acad Athens, Bur Epidemiol Res, Athens, Greece

[48] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland

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

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

来源：

GUT | 2014年 / 63卷 / 01期

基金：

美国国家卫生研究院;

关键词：

Cancer Genetics; Molecular Epidemiology; Pancreatic Cancer; CANCER RISK; GENE POLYMORPHISMS; SBF2; SUSCEPTIBILITY; GEMCITABINE; NEUROPATHY; MUTATIONS; VARIANTS; INSULIN; OBESITY;

D O I：

10.1136/gutjnl-2012-303477

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background and objective Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. Methods We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p10(-5)) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). Results In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63x10(-7)), rs981621 (p=1.65x10(-7)) and rs16861827 (p=3.75x10(-7)), respectively. 131 SNPs with p10(-5) were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72x10(-7)) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. Conclusions Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.

引用

页码：152 / 160

页数：9