TY  - JOUR
AU  - Laskar, R. S.
AU  - Qu, C.
AU  - Huyghe, J. R.
AU  - Harrison, T.
AU  - Hayes, R. B.
AU  - Cao, Y.
AU  - Campbell, P. T.
AU  - Steinfelder, R.
AU  - Talukdar, F. R.
AU  - Brenner, H.
AU  - Ogino, S.
AU  - Brendt, S.
AU  - Bishop, D. T.
AU  - Buchanan, D. D.
AU  - Chan, A. T.
AU  - Cotterchio, M.
AU  - Gruber, S. B.
AU  - Gsur, A.
AU  - van Guelpen, B.
AU  - Jenkins, M. A.
AU  - Keku, T. O.
AU  - Lynch, B. M.
AU  - Le Marchand, L.
AU  - Martin, R. M.
AU  - McCarthy, K.
AU  - Moreno, V.
AU  - Pearlman, R.
AU  - Song, M.
AU  - Tsilidis, K. K.
AU  - Vodička, P.
AU  - Woods, M. O.
AU  - Wu, K.
AU  - Hsu, L.
AU  - Gunter, M. J.
AU  - Peters, U.
AU  - Murphy, N.
TI  - Genome-wide association study and Mendelian randomization analyses provide insights into the causes of early-onset colorectal cancer.
JO  - Annals of oncology
VL  - 35
IS  - 6
SN  - 0923-7534
CY  - Amsterdam [u.a.
PB  - Elsevier
M1  - DKFZ-2024-00432
SP  - 523-536
PY  - 2024
N1  - 2024 Jun;35(6):523-536
AB  - The incidence of early-onset colorectal cancer (EOCRC; diagnosed <50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. Colorectal cancer (CRC) has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC.We conducted a genome-wide association study meta-analysis of 6,176 EOCRC cases and 65,829 controls from Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Colorectal Transdisciplinary study (CORECT), Colon Cancer Family Registry (CCFR), and UK Biobank. We then used the EOCRC GWAS to investigate 28 modifiable risk factors using two-sample Mendelian randomization (MR).We found two novel risk loci for EOCRC at 1p34.1 and 4p15.33, not previously associated with CRC risk. We identified a deleterious coding variant (rs36053993, G396D) at polyposis-associated DNA repair gene MUTYH (OR=1.80 [95
KW  - Early-onset colorectal cancer (Other)
KW  - GWAS (Other)
KW  - Mendelian randomization (Other)
KW  - genetics (Other)
KW  - risk factors (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:38408508
DO  - DOI:10.1016/j.annonc.2024.02.008
UR  - https://inrepo02.dkfz.de/record/288713
ER  -