Citations 42
Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia
Kocarnik, Jonathan , Lindor, Noralane M. , Chang‐Claude, Jenny , Caberto, Christian, Love, Shelly-Ann, Slattery, Martha L. , Hindorff, Lucia A. , Park, Sungshim Lani, Schumacher, Fredrick R. , Hoffmeister, Michael , Duggan, David , Hou, Lifang , Carlson, Chris , Carty, Cara L. , Mann, Sue, Giovannucci, Edward L. , Fuchs, Charles S. , Jenkins, Mark A. , Haile, Robert W. , Conti, David V. , Potter, John D. , Caan, Bette J. , Hayes, Richard B. , Berndt, Sonja I. , Küry, Sébastien , Bezieau, Stéphane , Ambite, José Luis , Kumaraguruparan, Gowri, Richardson, Danielle , Goodloe, Robert, Dilks, Holli H., Baker, Paxton, Zanke, Brent W., Lemire, Mathieu , Gallinger, Steven , Jiao, Shuo , Harrison, Tabitha A. , Seminara, Daniela, Haiman, Christopher A. , Hutter, Carolyn M., Crawford, Dana C. , Heiss, Gerardo , Brenner, Hermann , Bush, William S. , Casey, Graham , Peters, Ulrike , Cheng, Iona C. , Dumitrescu, Logan , Avery, Christy L. , Chan, Andrew T. , Baron, John A. , Kraft, Peter , Butler, Anne Marie E. , Monroe, Kristine R. , Lin, Yi , Ma, Jing , Newcomb, Polly A. , Hopper, John L. , Campbell, Peter T. , Schoen, Robert E. , Chanock, Stephen Jacob , Hsu, Li , Kooperberg, Charles , Wilkens, Lynne R. , White, Emily E. , Hudson, Thomas J , Marchand, Loı̈c Le , Hoffmeister, Michael , Jenkins, Mark A , Haile, Robert W , Harrison, Tabitha A , Potter, John D , Kury, Sebastien , Brenner, Hermann , Hayes, Richard B , Bézieau, Stéphane , Conti, David V , Hou, Lifang , Caan, Bette J , Bush, William S
Gut | August 10, 2013 | Volume: 63 | Issue: 5 | Pages: 800-807
Objective Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. Design We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92×10 −4 was used to determine statistical significance of the associations. Results Two correlated SNPs—rs10090154 and rs4242382—in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI 1.07 to 1.18; p=1.74×10 −5 ), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. Conclusions This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24.
Genome-wide association study of survival in patients with pancreatic adenocarcinoma
Wu, Chen , Steplowski, Emily, Brotzman, Michelle, Xu, Mousheng, Mudgal, Poorva, Ámundadóttir, Laufey T. , Arslan, Alan A. , Bueno‐de‐Mesquita, H. Bas, Gross, Myron D., Helzlsouer, Kathy J., Jacobs, Eric J. , Petersen, Gloria M. , Zheng, Wei , Buring, Julie E. , Canzian, Federico , Cao, Guangwen , Duell, Eric J. , Elena, Joanne W. , Gaziano, J. Michael , Giovannucci, Edward L. , Hallmans, Göran, Hutchinson, Amy , Hunter, David J., Jenab, Mazda , Jiang, Guoliang , LaCroix, Andrea Z. , Li, Zhaoshen , Mendelsohn, Julie B., Panico, Salvatore , Patel, Alpa V. , Qian, Zhi Rong , Ríboli, Elio , Sesso, Howard D. , Shen, Hongbing , Shu, Xiao‐Ou , Tjønneland, Anne , Tobias, Geoffrey S. , Trichopoulos, Dimitrios, Virtamo, Jarmo, Visvanathan, Kala , Wactawski‐Wende, Jean , Wang, Chengfeng , Yu, Kai , Zeleniuch‐Jacquotte, Anne , Hoover, Robert N. , Hartge, Patricia, Fuchs, Charles S. , Lin, Dongxin , Wolpin, Brian M. , Kraft, Peter , Stolzenberg‐Solomon, Rachael Z. , Kooperberg, Charles , Albanes, Demetrius , Boutron‐Ruault, Marie‐Christine , Khaw, Kay‐Tee , Chanock, Stephen Jacob , Amundadottir, Laufey , Duell, Eric J , Arslan, Alan A , Canzian, Federico , Tjønneland, Anne , Wactawski-Wende, Jean , Shu, Xiao-Ou , Visvanathan, Kala , Jenab, Mazda , Zheng, Wei , Cao, Guangwen , Riboli, Elio , Zeleniuch-Jacquotte, Anne , Shen, Hongbing
Gut | November 24, 2012 | Volume: 63 | Issue: 1 | Pages: 152-160
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 (p≤10 −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=1.63×10 −7 ), rs981621 (p=1.65×10 −7 ) and rs16861827 (p=3.75×10 −7 ), respectively. 131 SNPs with p≤10 −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=1.72×10 −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.