Journal Article

DKFZ-2020-00014

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cumulative Burden of Colorectal Cancer-Associated Genetic Variants is More Strongly Associated With Early-onset vs Late-onset Cancer.

Archambault, A. N. ; Su, Y.-R. ; Jeon, J. ; Thomas, M. ; Lin, Y. ; Conti, D. V. ; Win, A. K. ; Sakoda, L. C. ; Lansdorp-Vogelaar, I. ; Peterse, E. F. ; Zauber, A. G. ; Duggan, D. ; Holowatyj, A. N. ; Huyghe, J. R. ; Brenner, H.DKFZ* ; Cotterchio, M. ; Bézieau, S. ; Schmit, S. L. ; Edlund, C. K. ; Southey, M. C. ; MacInnis, R. J. ; Campbell, P. T. ; Chang-Claude, J.DKFZ* ; Slattery, M. L. ; Chan, A. T. ; Joshi, A. D. ; Song, M. ; Cao, Y. ; Woods, M. O. ; White, E. ; Weinstein, S. J. ; Ulrich, C. M. ; Hoffmeister, M.DKFZ* ; Bien, S. A. ; Harrison, T. A. ; Hampe, J. ; Li, C. I. ; Schafmayer, C. ; Offit, K. ; Pharoah, P. D. ; Moreno, V. ; Lindblom, A. ; Wolk, A. ; Wu, A. H. ; Li, L. ; Gunter, M. J. ; Gsur, A. ; Keku, T. O. ; Pearlman, R. ; Bishop, D. T. ; Castellví-Bel, S. ; Moreira, L. ; Vodicka, P. ; Kampman, E. ; Giles, G. G. ; Albanes, D. ; Baron, J. A. ; Berndt, S. I. ; Brezina, S. ; Buch, S. ; Buchanan, D. D. ; Trichopoulou, A. ; Severi, G. ; Chirlaque, M.-D. ; Sánchez, M.-J. ; Palli, D. ; Kühn, T.DKFZ* ; Murphy, N. ; Cross, A. J. ; Burnett-Hartman, A. N. ; Chanock, S. J. ; Chapelle, A. d. l. ; Easton, D. F. ; Elliott, F. ; English, D. R. ; Feskens, E. J. ; FitzGerald, L. M. ; Goodman, P. J. ; Hopper, J. L. ; Hudson, T. J. ; Hunter, D. J. ; Jacobs, E. J. ; Joshu, C. E. ; Küry, S. ; Markowitz, S. D. ; Milne, R. L. ; Platz, E. A. ; Rennert, G. ; Rennert, H. S. ; Schumacher, F. R. ; Sandler, R. S. ; Seminara, D. ; Tangen, C. M. ; Thibodeau, S. N. ; Toland, A. E. ; van Duijnhoven, F. J. ; Visvanathan, K. ; Vodickova, L. ; Potter, J. D. ; Männistö, S. ; Weigl, K.DKFZ* ; Figueiredo, J. ; Martín, V. ; Larsson, S. C. ; Parfrey, P. S. ; Huang, W.-Y. ; Lenz, H.-J. ; Castelao, J. E. ; Gago-Dominguez, M. ; Muñoz-Garzón, V. ; Mancao, C. ; Haiman, C. A. ; Wilkens, L. R. ; Siegel, E. ; Barry, E. ; Younghusband, B. ; Van Guelpen, B. ; Harlid, S. ; Zeleniuch-Jacquotte, A. ; Liang, P. S. ; Du, M. ; Casey, G. ; Lindor, N. M. ; Le Marchand, L. ; Gallinger, S. J. ; Jenkins, M. A. ; Newcomb, P. A. ; Gruber, S. B. ; Schoen, R. E. ; Hampel, H. ; Corley, D. A. ; Hsu, L. ; Peters, U. ; Hayes, R. B.

2020
Saunders Philadelphia, Pa. [u.a.]

This record in other databases:  

Please use a persistent id in citations: doi:10.1053/j.gastro.2019.12.012

Abstract: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single-nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction=.01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI, 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI, 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction=5.61x10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI, 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI, 2.70-3.00). Sensitivity analyses were consistent with these findings.In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer-particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventative measures.

Note: 2020 Apr;158(5):1274-1286.e12.

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Contributing Institute(s):

1. C070 Klinische Epidemiologie und Alternf. (C070)
2. Präventive Onkologie (C120)
3. DKTK HD zentral (HD01)
4. C020 Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2020

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; IF >= 20 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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