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000309674 1001_ $$aPeoples, Anita R$$b0
000309674 245__ $$aGenetic risk factors modulate the association between physical activity and colorectal cancer.
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000309674 520__ $$aPhysical activity is an established protective factor for colorectal cancer (CRC), but it is unclear if genetic variants modify this effect. To investigate this possibility, we conducted a genome-wide gene-physical activity interaction analysis.Using logistic regression (1-d.f), two-step screening and testing method (EDGE), and joint tests (3-d.f), we analyzed interactions between common genetic variants across the genome and physical activity in relation to CRC risk. Self-reported physical activity levels were categorized as active (≥ 8.75 MET-h/wk) vs. inactive (< 8.75 MET-h/wk; 39,992 participants) and as study- and sex-specific quartiles of activity (42,602 participants).Physical activity was inversely associated with CRC risk overall (OR [active vs. inactive] = 0.85; 95% CI = 0.81-0.90). The two-step EDGE method identified an interaction between rs4779584, an intergenic variant near the GREM1 and SCG5 genes, and physical activity for CRC risk (p-interaction = 2.6 × 10-8). Stratification by genotype at this locus showed a significant reduction in CRC risk by 20% in active vs. inactive participants with the CC genotype (OR = 0.80; 95% CI = 0.75-0.85), but no significant physical activity-CRC associations among CT or TT carriers. When physical activity was modeled as quartiles, the 1-d.f. test identified that rs56906466, an intergenic variant near the KCNG1 gene, modified the association between physical activity and CRC (p-interaction = 3.5 × 10-8). Stratification at this locus showed that an increase in physical activity (highest vs. lowest quartile) was associated with a lower CRC risk solely among TT carriers (OR = 0.77; 95% CI = 0.72-0.82).In summary, we identified two genetic variants that modified the association between physical activity and CRC risk. One of them, related to GREM1 and SCG5, suggests that the bone morphogenetic protein (BMP)-related, inflammatory, and/or insulin signaling pathways may be involved in the protective association between physical activity and colorectal carcinogenesis.
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000309674 650_7 $$2Other$$aColorectal cancer
000309674 650_7 $$2Other$$aGWAS
000309674 650_7 $$2Other$$aGene-environment interaction
000309674 650_7 $$2Other$$aPhysical activity
000309674 7001_ $$aObón-Santacana, Mireia$$b1
000309674 7001_ $$aKim, Andre E$$b2
000309674 7001_ $$aKawaguchi, Eric S$$b3
000309674 7001_ $$aFu, Yubo$$b4
000309674 7001_ $$aQu, Conghui$$b5
000309674 7001_ $$aMoratalla-Navarro, Ferran$$b6
000309674 7001_ $$aMorrison, John$$b7
000309674 7001_ $$aLin, Yi$$b8
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000309674 7001_ $$aBerndt, Sonja I$$b10
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000309674 7001_ $$aBishop, D Timothy$$b12
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000309674 7001_ $$aBuchanan, Daniel D$$b15
000309674 7001_ $$aCampbell, Peter T$$b16
000309674 7001_ $$aChan, Andrew T$$b17
000309674 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b18
000309674 7001_ $$aConti, David V$$b19
000309674 7001_ $$aCorley, Douglas Ac$$b20
000309674 7001_ $$aDevall, Matthew A$$b21
000309674 7001_ $$aDimou, Niki$$b22
000309674 7001_ $$aDrew, David A$$b23
000309674 7001_ $$aGruber, Stephen B$$b24
000309674 7001_ $$aGunter, Marc J$$b25
000309674 7001_ $$aHarlid, Sophia$$b26
000309674 7001_ $$aHarrison, Tabitha A$$b27
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000309674 7001_ $$aHsu, Li$$b29
000309674 7001_ $$aHuyghe, Jeroen R$$b30
000309674 7001_ $$aKeku, Temitope O$$b31
000309674 7001_ $$aKundaje, Anshul$$b32
000309674 7001_ $$aLewinger, Juan Pablo$$b33
000309674 7001_ $$aLi, Li$$b34
000309674 7001_ $$aLynch, Brigid M$$b35
000309674 7001_ $$aLe Marchand, Loic$$b36
000309674 7001_ $$aMartín, Vicente$$b37
000309674 7001_ $$aMurphy, Neil$$b38
000309674 7001_ $$aNewton, Christina C$$b39
000309674 7001_ $$aOgino, Shuji$$b40
000309674 7001_ $$aHardikar, Sheetal$$b41
000309674 7001_ $$aOse, Jennifer$$b42
000309674 7001_ $$aPai, Rish K$$b43
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000309674 7001_ $$aMoreno, Victor$$b73
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