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Genetic associations with sporadic neuroendocrine tumor risk.

Authors
Ter-Minassian-M; Wang-Z; Asomaning-K; Wu-MC; Liu-C-Y; Paulus-JK; Liu-G; Bradbury-PA; Zhai-R; Su-L; Frauenhoffer-CS; Hooshmand-SM; De Vivo-I; Lin-X; Christiani-DC; Kulke-MH
Source
Carcinogenesis 2011 Aug; 32(8):1216-1222
NIOSHTIC No.
20039747
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.
Keywords
Tumors; Endocrine-function; Endocrine-system; Endocrine-system-disorders; Humans; Men; Biological-factors; Biological-function; Biomarkers; Age-groups; Genetics; Genetic-factors; Genes; Risk-factors
Contact
Monica Ter-Minassian, Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115
CODEN
CRNGDP
Publication Date
20110801
Document Type
Journal Article
Email Address
mtermina@hsph.harvard.edu
Funding Type
Grant
Fiscal Year
2011
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-T42-OH-008416; B10122011
Issue of Publication
8
ISSN
0143-3334
Source Name
Carcinogenesis
State
MA
Performing Organization
Harvard School of Public Health
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