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000148822 0247_ $$2doi$$a10.1053/j.gastro.2019.12.012
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000148822 1001_ $$aArchambault, Alexi N$$b0
000148822 245__ $$aCumulative Burden of Colorectal Cancer-Associated Genetic Variants is More Strongly Associated With Early-onset vs Late-onset Cancer.
000148822 260__ $$aPhiladelphia, Pa. [u.a.]$$bSaunders$$c2020
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000148822 500__ $$a2020 Apr;158(5):1274-1286.e12.
000148822 520__ $$aEarly-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.
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000148822 7001_ $$aSu, Yu-Ru$$b1
000148822 7001_ $$aJeon, Jihyoun$$b2
000148822 7001_ $$aThomas, Minta$$b3
000148822 7001_ $$aLin, Yi$$b4
000148822 7001_ $$aConti, David V$$b5
000148822 7001_ $$aWin, Aung Ko$$b6
000148822 7001_ $$aSakoda, Lori C$$b7
000148822 7001_ $$aLansdorp-Vogelaar, Iris$$b8
000148822 7001_ $$aPeterse, Elisabeth Fp$$b9
000148822 7001_ $$aZauber, Ann G$$b10
000148822 7001_ $$aDuggan, David$$b11
000148822 7001_ $$aHolowatyj, Andreana N$$b12
000148822 7001_ $$aHuyghe, Jeroen R$$b13
000148822 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b14$$udkfz
000148822 7001_ $$aCotterchio, Michelle$$b15
000148822 7001_ $$aBézieau, Stéphane$$b16
000148822 7001_ $$aSchmit, Stephanie L$$b17
000148822 7001_ $$aEdlund, Christopher K$$b18
000148822 7001_ $$aSouthey, Melissa C$$b19
000148822 7001_ $$aMacInnis, Robert J$$b20
000148822 7001_ $$aCampbell, Peter T$$b21
000148822 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b22$$udkfz
000148822 7001_ $$aSlattery, Martha L$$b23
000148822 7001_ $$aChan, Andrew T$$b24
000148822 7001_ $$aJoshi, Amit D$$b25
000148822 7001_ $$aSong, Mingyang$$b26
000148822 7001_ $$aCao, Yin$$b27
000148822 7001_ $$aWoods, Michael O$$b28
000148822 7001_ $$aWhite, Emily$$b29
000148822 7001_ $$aWeinstein, Stephanie J$$b30
000148822 7001_ $$aUlrich, Cornelia M$$b31
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000148822 7001_ $$aHampe, Jochen$$b35
000148822 7001_ $$aLi, Christopher I$$b36
000148822 7001_ $$aSchafmayer, Clemens$$b37
000148822 7001_ $$aOffit, Kenneth$$b38
000148822 7001_ $$aPharoah, Paul D$$b39
000148822 7001_ $$aMoreno, Victor$$b40
000148822 7001_ $$aLindblom, Annika$$b41
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000148822 7001_ $$aWu, Anna H$$b43
000148822 7001_ $$aLi, Li$$b44
000148822 7001_ $$aGunter, Marc J$$b45
000148822 7001_ $$aGsur, Andrea$$b46
000148822 7001_ $$aKeku, Temitope O$$b47
000148822 7001_ $$aPearlman, Rachel$$b48
000148822 7001_ $$aBishop, D Timothy$$b49
000148822 7001_ $$aCastellví-Bel, Sergi$$b50
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000148822 7001_ $$aVodicka, Pavel$$b52
000148822 7001_ $$aKampman, Ellen$$b53
000148822 7001_ $$aGiles, Graham G$$b54
000148822 7001_ $$aAlbanes, Demetrius$$b55
000148822 7001_ $$aBaron, John A$$b56
000148822 7001_ $$aBerndt, Sonja I$$b57
000148822 7001_ $$aBrezina, Stefanie$$b58
000148822 7001_ $$aBuch, Stephan$$b59
000148822 7001_ $$aBuchanan, Daniel D$$b60
000148822 7001_ $$aTrichopoulou, Antonia$$b61
000148822 7001_ $$aSeveri, Gianluca$$b62
000148822 7001_ $$aChirlaque, María-Dolores$$b63
000148822 7001_ $$aSánchez, Maria-José$$b64
000148822 7001_ $$aPalli, Domenico$$b65
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000148822 7001_ $$aGoodman, Phyllis J$$b77
000148822 7001_ $$aHopper, John L$$b78
000148822 7001_ $$aHudson, Thomas J$$b79
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000148822 7001_ $$aJoshu, Corinne E$$b82
000148822 7001_ $$aKüry, Sébastien$$b83
000148822 7001_ $$aMarkowitz, Sanford D$$b84
000148822 7001_ $$aMilne, Roger L$$b85
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000148822 7001_ $$aRennert, Gad$$b87
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