TY - JOUR
T1 - Genome-wide association study identifies tumor anatomical site-specific risk variants for colorectal cancer survival
AU - Labadie, Julia D.
AU - Savas, Sevtap
AU - Harrison, Tabitha A.
AU - Banbury, Barb
AU - Huang, Yuhan
AU - Buchanan, Daniel D.
AU - Campbell, Peter T.
AU - Gallinger, Steven J.
AU - Giles, Graham G.
AU - Gunter, Marc J.
AU - Hoffmeister, Michael
AU - Hsu, Li
AU - Jenkins, Mark A.
AU - Lin, Yi
AU - Ogino, Shuji
AU - Phipps, Amanda I.
AU - Slattery, Martha L.
AU - Steinfelder, Robert S.
AU - Sun, Wei
AU - Van Guelpen, Bethany
AU - Hua, Xinwei
AU - Figuieredo, Jane C.
AU - Pai, Rish K.
AU - Nassir, Rami
AU - Qi, Lihong
AU - Chan, Andrew T.
AU - Peters, Ulrike
AU - Newcomb, Polly A.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Identification of new genetic markers may improve the prediction of colorectal cancer prognosis. Our objective was to examine genome-wide associations of germline genetic variants with disease-specific survival in an analysis of 16,964 cases of colorectal cancer. We analyzed genotype and colorectal cancer-specific survival data from a consortium of 15 studies. Approximately 7.5 million SNPs were examined under the log-additive model using Cox proportional hazards models, adjusting for clinical factors and principal components. Additionally, we ran secondary analyses stratifying by tumor site and disease stage. We used a genome-wide p-value threshold of 5 × 10–8 to assess statistical significance. No variants were statistically significantly associated with disease-specific survival in the full case analysis or in the stage-stratified analyses. Three SNPs were statistically significantly associated with disease-specific survival for cases with tumors located in the distal colon (rs698022, HR = 1.48, CI 1.30–1.69, p = 8.47 × 10–9) and the proximal colon (rs189655236, HR = 2.14, 95% CI 1.65–2.77, p = 9.19 × 10–9 and rs144717887, HR = 2.01, 95% CI 1.57–2.58, p = 3.14 × 10–8), whereas no associations were detected for rectal tumors. Findings from this large genome-wide association study highlight the potential for anatomical-site-stratified genome-wide studies to identify germline genetic risk variants associated with colorectal cancer-specific survival. Larger sample sizes and further replication efforts are needed to more fully interpret these findings.
AB - Identification of new genetic markers may improve the prediction of colorectal cancer prognosis. Our objective was to examine genome-wide associations of germline genetic variants with disease-specific survival in an analysis of 16,964 cases of colorectal cancer. We analyzed genotype and colorectal cancer-specific survival data from a consortium of 15 studies. Approximately 7.5 million SNPs were examined under the log-additive model using Cox proportional hazards models, adjusting for clinical factors and principal components. Additionally, we ran secondary analyses stratifying by tumor site and disease stage. We used a genome-wide p-value threshold of 5 × 10–8 to assess statistical significance. No variants were statistically significantly associated with disease-specific survival in the full case analysis or in the stage-stratified analyses. Three SNPs were statistically significantly associated with disease-specific survival for cases with tumors located in the distal colon (rs698022, HR = 1.48, CI 1.30–1.69, p = 8.47 × 10–9) and the proximal colon (rs189655236, HR = 2.14, 95% CI 1.65–2.77, p = 9.19 × 10–9 and rs144717887, HR = 2.01, 95% CI 1.57–2.58, p = 3.14 × 10–8), whereas no associations were detected for rectal tumors. Findings from this large genome-wide association study highlight the potential for anatomical-site-stratified genome-wide studies to identify germline genetic risk variants associated with colorectal cancer-specific survival. Larger sample sizes and further replication efforts are needed to more fully interpret these findings.
UR - https://www.scopus.com/pages/publications/85122569586
U2 - 10.1038/s41598-021-03945-x
DO - 10.1038/s41598-021-03945-x
M3 - Article
C2 - 34996992
AN - SCOPUS:85122569586
SN - 2045-2322
VL - 12
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 127
ER -