title: Genetic associations with sporadic neuroendocrine tumor risk.
abstract: Genetic risk factors for sporadic neuroendocrine tumors (NET) are poorly understood. We tested risk associations in patients with sporadic NET and non-cancer controls, using a custom array containing 1536 single-nucleotide polymorphisms (SNPs) in 355 candidate genes. We identified 18 SNPs associated with NET risk at a P-value <0.01 in a discovery set of 261 cases and 319 controls. Two of these SNPs were found to be significantly associated with NET risk in an independent replication set of 235 cases and 113 controls, at a P value ≤0.05. An SNP in interleukin 12A (IL12A rs2243123), a gene implicated in inflammatory response, replicated with an adjusted odds ratio (95% confidence interval) (aOR) = 1.47 (1.03, 2.11) P-trend = 0.04. A second SNP in defender against cell death, (DAD1 rs8005354), a gene that modulates apoptosis, replicated at aOR = 1.43 (1.02, 2.02) P-trend = 0.04. Consistent with our observations, a pathway analysis, performed in the discovery set, suggested that genetic variation in inflammatory pathways or apoptosis pathways is associated with NET risk. Our findings support further investigation of the potential role of IL12A and DAD1 in the etiology of NET.
authors: Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. mtermina@hsph.harvard.edu
authors: Monica
authors: M
authors: Ter-Minassian
authors: Zhaoxi
authors: Z
authors: Wang
authors: Kofi
authors: K
authors: Asomaning
authors: Michael C
authors: MC
authors: Wu
authors: Chen-Yu
authors: CY
authors: Liu
authors: Jessica K
authors: JK
authors: Paulus
authors: Geoffrey
authors: G
authors: Liu
authors: Penelope A
authors: PA
authors: Bradbury
authors: Rihong
authors: R
authors: Zhai
authors: Li
authors: L
authors: Su
authors: Christine S
authors: CS
authors: Frauenhoffer
authors: Susanne M
authors: SM
authors: Hooshmand
authors: Immaculata
authors: I
authors: De Vivo
authors: Xihong
authors: X
authors: Lin
authors: David C
authors: DC
authors: Christiani
authors: Matthew H
authors: MH
authors: Kulke
references: J Clin Oncol. 2008 Jun 20;26(18):3063-72
references: 18565894
references: J Biol Chem. 1998 Oct 2;273(40):26094-9
references: 9748289
references: J Mol Med (Berl). 2010 Apr;88(4):423-9
references: 20049409
references: Am J Hum Genet. 2010 Jun 11;86(6):970-7
references: 20560212
references: PLoS Genet. 2007 Feb 23;3(2):e29
references: 17319747
references: PLoS Genet. 2007 Mar 16;3(3):e42
references: 17367212
references: Neuroendocrinology. 2010;91(4):318-23
references: 20460879
references: Nature. 2005 Oct 27;437(7063):1299-320
references: 16255080
references: J Immunol. 2001 Oct 1;167(7):3836-45
references: 11564801
references: Genes Chromosomes Cancer. 2008 Jul;47(7):591-603
references: 18383209
references: Endocr Relat Cancer. 2009 Sep;16(3):953-66
references: 19458023
references: Br J Haematol. 2011 May;153(3):318-33
references: 21418178
references: Clin Cancer Res. 2009 Jan 1;15(1):400-5
references: 19118071
references: Genes Immun. 2010 Jul;11(5):397-405
references: 20555355
references: Neuroendocrinology. 2006;84(5):346-52
references: 17164537
references: Clin Cancer Res. 2007 Aug 15;13(16):4677-85
references: 17699845
references: Nat Genet. 2010 Aug;42(8):658-60
references: 20639880
references: Int J Cancer. 2008 Aug 15;123(4):867-73
references: 18491401
references: Exp Mol Pathol. 2007 Dec;83(3):474-9
references: 17950274
references: Cancer Epidemiol Biomarkers Prev. 2010 Sep;19(9):2152-63
references: 20716621
references: J Med Genet. 2005 Jun;42(6):503-10
references: 15937086
references: Virchows Arch. 2007 Aug;451 Suppl 1:S29-38
references: 17684762
references: Cancer Res. 2000 Feb 15;60(4):1111-6
references: 10706132
references: Ann Surg. 2004 Jul;240(1):117-22
references: 15213627
references: Carcinogenesis. 2007 Jul;28(7):1437-41
references: 17361014
references: Clin Endocrinol (Oxf). 2007 Jan;66(1):1-6
references: 17201794
references: Cancer Res. 2002 May 15;62(10):2819-23
references: 12019159
references: Cancer Epidemiol Biomarkers Prev. 2005 Feb;14(2):491-6
references: 15734977
references: Carcinogenesis. 2008 Oct;29(10):1938-43
references: 18676680
references: Am J Gastroenterol. 2008 Mar;103(3):729-32
references: 18341492
references: Cancer Causes Control. 2002 Feb;13(1):27-34
references: 11899115
references: Br J Haematol. 2011 May;153(3):341-50
references: 21418175
references: Ann Oncol. 2009 May;20(5):950-4
references: 19150948
references: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W635-41
references: 16845089
references: Cancer Epidemiol Biomarkers Prev. 2008 Apr;17(4):959-65
references: 18398037
references: Cancer Epidemiol Biomarkers Prev. 2008 Feb;17(2):311-9
references: 18268114
references: Am Rev Respir Dis. 1978 Dec;118(6 Pt 2):1-120
references: 742764
references: Genet Epidemiol. 2006 Nov;30(7):636-43
references: 16986161
references: Nat Genet. 2008 Apr;40(4):395-402
references: 18311140