TY - JOUR
T1 - A germline variant on chromosome 4q31.1 associates with susceptibility to developing colon cancer metastasis
AU - Markowitz, Sanford D.
AU - Nock, Nora L.
AU - Schmit, Stephanie L.
AU - Stadler, Zsofia K.
AU - Joseph, Vijai
AU - Zhang, Lu
AU - Willis, Joseph E.
AU - Scacheri, Peter
AU - Veigl, Martina
AU - Adams, Mark D.
AU - Raskin, Leon
AU - Sullivan, John F.
AU - Stratton, Kelly
AU - Shia, Jinru
AU - Ellis, Nathan
AU - Rennert, Hedy S.
AU - Manschreck, Christopher
AU - Li, Li
AU - Offit, Kenneth
AU - Elston, Robert C.
AU - Rennert, Gadi
AU - Gruber, Stephen B.
N1 - Publisher Copyright:
Copyright © 2016 Markowitz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/1/11
Y1 - 2016/1/11
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84954565409
UR - https://www.scopus.com/pages/publications/84954565409#tab=citedBy
U2 - 10.1371/journal.pone.0146435
DO - 10.1371/journal.pone.0146435
M3 - Article
C2 - 26751797
AN - SCOPUS:84954565409
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 1
M1 - e0146435
ER -