Title: A Germline Variant on Chromosome 4q31.1 Associates with Susceptibility to Developing Colon Cancer Metastasis.
Authors: Markowitz, Sanford D; Nock, Nora L; Schmit, Stephanie L; Stadler, Zsofia K; Joseph, Vijai; Zhang, Lu; Willis, Joseph E; Scacheri, Peter; Veigl, Martina; Adams, Mark D; Raskin, Leon; Sullivan, John F; Stratton, Kelly; Shia, Jinru; Ellis, Nathan; Rennert, Hedy S; Manschreck, Christopher; Li, Li; Offit, Kenneth; Elston, Robert C; Rennert, Gadi; Gruber, Stephen B
Published In PLoS One, (2016)
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.
PubMed ID: 26751797
MeSH Terms: Aged; Chromosomes, Human, Pair 4/genetics*; Cohort Studies; Colonic Neoplasms/ethnology; Colonic Neoplasms/genetics*; Colonic Neoplasms/pathology*; Female; Genetic Predisposition to Disease; Genome, Human; Genome-Wide Association Study; Genotype; Germ-Line Mutation*; Haplotypes; Humans; Jews; Linkage Disequilibrium; Male; Middle Aged; Models, Statistical; Neoplasm Metastasis/genetics*; Neoplasm Metastasis/pathology; Odds Ratio; Polymorphism, Single Nucleotide