A Germline Variant on Chromosome 4q31.1 Associates with Susceptibility to Developing Colon Cancer Metastasis
Year: 2016
Type: article
Study design: Observational Study
Abstract: We tested for germline variants showing association to colon cancer metastasis using a genome-wide association study that compared Ashkenazi Jewish individuals with stage IV metastatic colon cancers versus those with stage I or II non-metastatic colon cancers. In a two-stage study design, we demonstrated significant association to developing metastatic disease for rs60745952, that in Ashkenazi discovery and validation cohorts, respectively, showed an odds ratio (OR) = 2.3 (P = 2.73E-06) and OR = 1.89 (P = 8.05E-04) (exceeding validation threshold of 0.0044). Significant association to metastatic colon cancer was further confirmed by a meta-analysis of rs60745952 in these datasets plus an additional Ashkenazi validation cohort (OR = 1.92; 95% CI: 1.28-2.87), and by a permutation test that demonstrated a significantly longer haplotype surrounding rs60745952 in the stage IV samples. rs60745952, located in an intergenic region on chromosome 4q31.1, and not previously associated with cancer, is, thus, a germline genetic marker for susceptibility to developing colon cancer metastases among Ashkenazi Jews.
Source: PLoS ONE
Authors: Sanford D. Markowitz, Nora L. Nock, Stephanie L. Schmit, Zsofia K. Stadler, Vijai Joseph, Lu Zhang, Joseph E. Willis, Peter Scacheri, Martina Veigl, Mark D. Adams, Leon Raskin, John F. Sullivan, Kelly Stratton, Jinru Shia, Nathan Ellis, Hedy S. Rennert, Christopher Manschreck, Li Li, Kenneth Offit, Robert C. Elston, Gadi Rennert, Stephen B. Gruber
Institutions: Case Comprehensive Cancer Center, Case Western Reserve University, University of Southern California, USC Norris Comprehensive Cancer Center, Memorial Sloan Kettering Cancer Center, Vanderbilt University, University of Arizona Cancer Center, Technion – Israel Institute of Technology, Carmel Medical Center, Clalit Health Services
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: G1096387360, Genetic risk factors in African American colorectal cancer patients, G1480891745, Transdisciplinary Studies of Genetic Variation in Colorectal Cancer, Obesity-Related Insulin Resistance Signaling Pathway Factors and Colon Cancer, G3913265907, G4637436490, G5716778331, G6101372004, The role of gene enhancer elements in colon cancer, G7162541680, Case GI SPORE, G9000108948, G9000143528, G9000202443, G9000284690, Cancer Center Support Grant, Case Comprehensive Cancer Center Support Grant, University of Southern California Norris Comprehensive Cancer Center Support Grant (CCSG)
OpenAlex ID: W2233717710