OBJECTIVE: The objective of this study was to fine-map common pancreatic cancer susceptibility regions. METHODS: We conducted targeted Roche-454 resequencing across 428 kb in 3 genomic regions identified in genome-wide association studies (GWAS) of pancreatic cancer, on chromosomes 1q32.1, 5p15.33, and 13q22.1. RESULTS: An analytical pipeline for calling genotypes was developed using HapMap samples sequenced on chr5p15.33. Concordance to 1000 Genomes data for chr5p15.33 was greater than 96%. The concordance for chr1q32.1 and chr13q22.1 with pancreatic cancer GWAS data was greater than 99%. Between 9.2% and 19.0% of variants detected were not present in 1000 Genomes for the respective continental population. The majority of completely novel single-nucleotide polymorphisms (SNPs) were less common (minor allele frequency [MAF], ≤5%) or rare (MAF, ≤2%), illustrating the value of enlarging test sets for discovery of less common variants. Using the data set, we examined haplotype blocks across each region using a tag SNP analysis (r² > 0.8 for MAF of ≥5%) and determined that at least 196, 243, and 63 SNPs are required for fine-mapping chr1q32.1, chr5p15.33, and chr13q22.1, respectively, in European populations. CONCLUSIONS: We have characterized germline variation in 3 regions associated with pancreatic cancer risk and show that targeted resequencing leads to the discovery of novel variants and improves the completeness of germline sequence variants for fine-mapping GWAS susceptibility loci.
OBJECTIVE: The objective of this study was to fine-map common pancreatic cancer susceptibility regions. METHODS: We conducted targeted Roche-454 resequencing across 428 kb in 3 genomic regions identified in genome-wide association studies (GWAS) of pancreatic cancer, on chromosomes 1q32.1, 5p15.33, and 13q22.1. RESULTS: An analytical pipeline for calling genotypes was developed using HapMap samples sequenced on chr5p15.33. Concordance to 1000 Genomes data for chr5p15.33 was greater than 96%. The concordance for chr1q32.1 and chr13q22.1 with pancreatic cancer GWAS data was greater than 99%. Between 9.2% and 19.0% of variants detected were not present in 1000 Genomes for the respective continental population. The majority of completely novel single-nucleotide polymorphisms (SNPs) were less common (minor allele frequency [MAF], ≤5%) or rare (MAF, ≤2%), illustrating the value of enlarging test sets for discovery of less common variants. Using the data set, we examined haplotype blocks across each region using a tag SNP analysis (r² > 0.8 for MAF of ≥5%) and determined that at least 196, 243, and 63 SNPs are required for fine-mapping chr1q32.1, chr5p15.33, and chr13q22.1, respectively, in European populations. CONCLUSIONS: We have characterized germline variation in 3 regions associated with pancreatic cancer risk and show that targeted resequencing leads to the discovery of novel variants and improves the completeness of germline sequence variants for fine-mapping GWAS susceptibility loci.
Authors: N W Kim; M A Piatyszek; K R Prowse; C B Harley; M D West; P L Ho; G M Coviello; W E Wright; S L Weinrich; J W Shay Journal: Science Date: 1994-12-23 Impact factor: 47.728
Authors: Gloria M Petersen; Laufey Amundadottir; Charles S Fuchs; Peter Kraft; Rachael Z Stolzenberg-Solomon; Kevin B Jacobs; Alan A Arslan; H Bas Bueno-de-Mesquita; Steven Gallinger; Myron Gross; Kathy Helzlsouer; Elizabeth A Holly; Eric J Jacobs; Alison P Klein; Andrea LaCroix; Donghui Li; Margaret T Mandelson; Sara H Olson; Harvey A Risch; Wei Zheng; Demetrius Albanes; William R Bamlet; Christine D Berg; Marie-Christine Boutron-Ruault; Julie E Buring; Paige M Bracci; Federico Canzian; Sandra Clipp; Michelle Cotterchio; Mariza de Andrade; Eric J Duell; J Michael Gaziano; Edward L Giovannucci; Michael Goggins; Göran Hallmans; Susan E Hankinson; Manal Hassan; Barbara Howard; David J Hunter; Amy Hutchinson; Mazda Jenab; Rudolf Kaaks; Charles Kooperberg; Vittorio Krogh; Robert C Kurtz; Shannon M Lynch; Robert R McWilliams; Julie B Mendelsohn; Dominique S Michaud; Hemang Parikh; Alpa V Patel; Petra H M Peeters; Aleksandar Rajkovic; Elio Riboli; Laudina Rodriguez; Daniela Seminara; Xiao-Ou Shu; Gilles Thomas; Anne Tjønneland; Geoffrey S Tobias; Dimitrios Trichopoulos; Stephen K Van Den Eeden; Jarmo Virtamo; Jean Wactawski-Wende; Zhaoming Wang; Brian M Wolpin; Herbert Yu; Kai Yu; Anne Zeleniuch-Jacquotte; Joseph F Fraumeni; Robert N Hoover; Patricia Hartge; Stephen J Chanock Journal: Nat Genet Date: 2010-01-24 Impact factor: 38.330
Authors: Alan A Arslan; Kathy J Helzlsouer; Charles Kooperberg; Xiao-Ou Shu; Emily Steplowski; H Bas Bueno-de-Mesquita; Charles S Fuchs; Myron D Gross; Eric J Jacobs; Andrea Z Lacroix; Gloria M Petersen; Rachael Z Stolzenberg-Solomon; Wei Zheng; Demetrius Albanes; Laufey Amundadottir; William R Bamlet; Aurelio Barricarte; Sheila A Bingham; Heiner Boeing; Marie-Christine Boutron-Ruault; Julie E Buring; Stephen J Chanock; Sandra Clipp; J Michael Gaziano; Edward L Giovannucci; Susan E Hankinson; Patricia Hartge; Robert N Hoover; David J Hunter; Amy Hutchinson; Kevin B Jacobs; Peter Kraft; Shannon M Lynch; Jonas Manjer; Joann E Manson; Anne McTiernan; Robert R McWilliams; Julie B Mendelsohn; Dominique S Michaud; Domenico Palli; Thomas E Rohan; Nadia Slimani; Gilles Thomas; Anne Tjønneland; Geoffrey S Tobias; Dimitrios Trichopoulos; Jarmo Virtamo; Brian M Wolpin; Kai Yu; Anne Zeleniuch-Jacquotte; Alpa V Patel Journal: Arch Intern Med Date: 2010-05-10
Authors: Fatemeh Kaveh; Lars O Baumbusch; Daniel Nebdal; Anne-Lise Børresen-Dale; Ole Christian Lingjærde; Hege Edvardsen; Vessela N Kristensen; Hiroko K Solvang Journal: BMC Cancer Date: 2016-11-22 Impact factor: 4.430