A Germline Variant on Chromosome 4q31.1 Associates with Susceptibility to Developing Colon Cancer Metastasis

作者：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

来源：PLos One, 2016, 11(1): e0146435.

DOI：10.1371/journal.pone.0146435

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.

• 出版日期2016-1-11