@article{3101399,
    title = "Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21",
    author = "Zhang, M. and Wang, Z. and Obazee, O. and Jia, J. and Childs, E.J. and Hoskins, J. and Figlioli, G. and Mocci, E. and Collins, I. and Chung, C.C. and Hautman, C. and Arslan, A.A. and Beane-Freeman, L. and Bracci, P.M. and Buring, J. and Duell, E.J. and Gallinger, S. and Giles, G.G. and Goodman, G.E. and Goodman, P.J. and Kamineni, A. and Kolonel, L.N. and Kulke, M.H. and Malats, N. and Olson, S.H. and Sesso, H.D. and Visvanathan, K. and White, E. and Zheng, W. and Abnet, C.C. and Albanes, D. and Andreotti, G. and Brais, L. and Bas Bueno-de-Mesquita, H. and Basso, D. and Berndt, S.I. and Boutron-Ruault, M.-C. and Bijlsma, M.F. and Brenner, H. and Burdette, L. and Campa, D. and Caporaso, N.E. and Capurso, G. and Cavestro, G.M. and Cotterchio, M. and Costello, E. and Elena, J. and Boggi, U. and Michael Gaziano, J. and Gazouli, M. and Giovannucci, E.L. and Goggins, M. and Gross, M. and Haiman, C.A. and Hassan, M. and Helzlsouer, K.J. and Hu, N. and Hunter, D.J. and Iskierka-Jazdzewska, E. and Jenab, M. and Kaaks, R. and Key, T.J. and Khaw, K.-T. and Klein, E.A. and Kogevinas, M. and Krogh, V. and Kupcinskas, J. and Kurtz, R.C. and Landi, M.T. and Landi, S. and Marchand, L.L. and Mambrini, A. and Mannisto, S. and Milne, R.L. and Neale, R.E. and Oberg, A.L. and Panico, S. and Patel, A.V. and Peeters, P.H.M. and Peters, U. and Pezzilli, R. and Porta, M. and Purdue, M. and Ramón Quiros, J. and Riboli, E. and Rothman, N. and Scarpa, A. and Scelo, G. and Shu, X.-O. and Silverman, D.T. and Soucek, P. and Strobel, O. and Sund, M. and Malecka-Panas, E. and Taylor, P.R. and Tavano, F. and Travis, R.C. and Thornquist, M. and Tjønneland, A. and Tobias, G.S. and Trichopoulos, D. and Vashist, Y. and Vodicka, P. and Wactawski-Wende, J. and Wentzensen, N. and Yu, H. and Yu, K. and Zeleniuch-Jacquotte, A. and Kooperberg, C. and Risch, H.A. and Jacobs, E.J. and Li, D. and Fuchs, C. and Hoover, R. and Hartge, P. and Chanock, S.J. and Petersen, G.M. and Stolzenberg-Solomon, R.S. and Wolpin, B.M. and Kraft, P. and Klein, A.P. and Canzian, F. and Amundadottir, L.T.",
    journal = "OncoTargets and therapy",
    year = "2016",
    volume = "7",
    number = "41",
    pages = "66328-66343",
    publisher = "Impact Journals, LLC",
    doi = "10.18632/oncotarget.11041",
    keywords = "liver receptor homolog 1;  Myc protein;  telomerase reverse transcriptase, Article;  bioinformatics;  cancer risk;  cancer susceptibility;  case control study;  chromosome;  chromosomes 1q32.1;  chromosomes 5p15.33;  chromosomes 8q24.21;  CLPTM1L gene;  controlled study;  down regulation;  gene expression;  gene frequency;  gene locus;  genetic association;  genetic risk;  genetic variability;  genome analysis;  histopathology;  human;  human tissue;  major clinical study;  NR5A2 gene;  oncogene;  oncogene myc;  pancreas cancer;  signal transduction;  single nucleotide polymorphism;  TERT gene;  chromosome 1;  chromosome 5;  chromosome 8;  genetic predisposition;  genetics;  genome-wide association study;  genotype;  information processing;  pancreas tumor;  procedures, Chromosomes, Human, Pair 1;  Chromosomes, Human, Pair 5;  Chromosomes, Human, Pair 8;  Datasets as Topic;  Genetic Predisposition to Disease;  Genome-Wide Association Study;  Genotype;  Humans;  Pancreatic Neoplasms;  Polymorphism, Single Nucleotide",
    abstract = "Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10-15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10-9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10-8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L-TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10-8). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10-4-2.0x10-3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology."
}