A germline variant on chromosome 4q31.1 associates with susceptibility to developing colon cancer metastasis

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. ElstonGadi Rennert, Stephen B. Gruber

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1 Scopus citations


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.

Original languageEnglish (US)
Article numbere0146435
JournalPloS one
Issue number1
StatePublished - Jan 11 2016

ASJC Scopus subject areas

  • General


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