RT Journal Article
T1 Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer.
A1 Archambault, Alexi N
A1 Su, Yu-Ru
A1 Jeon, Jihyoun
A1 Thomas, Minta
A1 Lin, Yi
A1 Conti, David V
A1 Win, Aung Ko
A1 Sakoda, Lori C
A1 Lansdorp-Vogelaar, Iris
A1 Peterse, Elisabeth F P
A1 Zauber, Ann G
A1 Duggan, David
A1 Holowatyj, Andreana N
A1 Huyghe, Jeroen R
A1 Brenner, Hermann
A1 Cotterchio, Michelle
A1 Bézieau, Stéphane
A1 Schmit, Stephanie L
A1 Edlund, Christopher K
A1 Southey, Melissa C
A1 MacInnis, Robert J
A1 Campbell, Peter T
A1 Chang-Claude, Jenny
A1 Slattery, Martha L
A1 Chan, Andrew T
A1 Joshi, Amit D
A1 Song, Mingyang
A1 Cao, Yin
A1 Woods, Michael O
A1 White, Emily
A1 Weinstein, Stephanie J
A1 Ulrich, Cornelia M
A1 Hoffmeister, Michael
A1 Bien, Stephanie A
A1 Harrison, Tabitha A
A1 Hampe, Jochen
A1 Li, Christopher I
A1 Schafmayer, Clemens
A1 Offit, Kenneth
A1 Pharoah, Paul D
A1 Moreno, Victor
A1 Lindblom, Annika
A1 Wolk, Alicja
A1 Wu, Anna H
A1 Li, Li
A1 Gunter, Marc J
A1 Gsur, Andrea
A1 Keku, Temitope O
A1 Pearlman, Rachel
A1 Bishop, D Timothy
A1 Castellví-Bel, Sergi
A1 Moreira, Leticia
A1 Vodicka, Pavel
A1 Kampman, Ellen
A1 Giles, Graham G
A1 Albanes, Demetrius
A1 Baron, John A
A1 Berndt, Sonja I
A1 Brezina, Stefanie
A1 Buch, Stephan
A1 Buchanan, Daniel D
A1 Trichopoulou, Antonia
A1 Severi, Gianluca
A1 Chirlaque, María-Dolores
A1 Sanchez-Perez, Maria-Jose
A1 Palli, Domenico
A1 Kühn, Tilman
A1 Murphy, Neil
A1 Cross, Amanda J
A1 Burnett-Hartman, Andrea N
A1 Chanock, Stephen J
A1 de la Chapelle, Albert
A1 Easton, Douglas F
A1 Elliott, Faye
A1 English, Dallas R
A1 Feskens, Edith J M
A1 FitzGerald, Liesel M
A1 Goodman, Phyllis J
A1 Hopper, John L
A1 Hudson, Thomas J
A1 Hunter, David J
A1 Jacobs, Eric J
A1 Joshu, Corinne E
A1 Küry, Sébastien
A1 Markowitz, Sanford D
A1 Milne, Roger L
A1 Platz, Elizabeth A
A1 Rennert, Gad
A1 Rennert, Hedy S
A1 Schumacher, Fredrick R
A1 Sandler, Robert S
A1 Seminara, Daniela
A1 Tangen, Catherine M
A1 Thibodeau, Stephen N
A1 Toland, Amanda E
A1 van Duijnhoven, Franzel J B
A1 Visvanathan, Kala
A1 Vodickova, Ludmila
A1 Potter, John D
A1 Männistö, Satu
A1 Weigl, Korbinian
A1 Figueiredo, Jane
A1 Martín, Vicente
A1 Larsson, Susanna C
A1 Parfrey, Patrick S
A1 Huang, Wen-Yi
A1 Lenz, Heinz-Josef
A1 Castelao, Jose E
A1 Gago-Dominguez, Manuela
A1 Muñoz-Garzón, Victor
A1 Mancao, Christoph
A1 Haiman, Christopher A
A1 Wilkens, Lynne R
A1 Siegel, Erin
A1 Barry, Elizabeth
A1 Younghusband, Ban
A1 Van Guelpen, Bethany
A1 Harlid, Sophia
A1 Zeleniuch-Jacquotte, Anne
A1 Liang, Peter S
A1 Du, Mengmeng
A1 Casey, Graham
A1 Lindor, Noralane M
A1 Le Marchand, Loic
A1 Gallinger, Steven J
A1 Jenkins, Mark A
A1 Newcomb, Polly A
A1 Gruber, Stephen B
A1 Schoen, Robert E
A1 Hampel, Heather
A1 Corley, Douglas A
A1 Hsu, Li
A1 Peters, Ulrike
A1 Hayes, Richard B
K1 Colon Cancer
K1 EOCRC
K1 Penetrance
K1 SNP
AB 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 = 5.61 × 10-5). 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 preventive measures.
YR 2019
FD 2019-12-19
LK http://hdl.handle.net/10668/14866
UL http://hdl.handle.net/10668/14866
LA en
DS RISalud
RD Apr 5, 2025