Citations 2
Genetic risk factors modulate the association between physical activity and colorectal cancer
Kim, Andre E., Fu, Yubo, Morrison, John, Lin, Yi, Berndt, Sonja, Chang-Claude, Jenny, Conti, David V., Corley, Douglas A. , Gruber, Stephen B. , Harlid, Sophia , Huyghe, Jeroen R. , Kundaje, Anshul , Martín, Vicente , Newton, Christina C. , Hardikar, Sheetal , Pai, Rish K. , Papadimitriou, Nikos , Pinchev, Mila, Schoen, Robert , Tsilidis, Konstantinos K, Duijnhoven, Franzel J. B. van, Visvanathan, Kala , Wolk, Alicja, Woods, Michael O. , Wu, Anna H. , Ulrich, Cornelia M. , Peters, Ulrike, Gauderman, W. James, Moreno, Victor, Martín, Vicente , Drew, David A. , Martín, Vicente , Drew, David A , Visvanathan, Kala , Kundaje, Anshul , Papadimitriou, Nikos , Peoples, Anita R , Obón‐Santacana, Mireia , Kawaguchi, Eric , Qu, Conghui , Moratalla-Navarro, Ferrán , Morrison, John, Arndt, Volker , Bien, Stephanie A. , Bishop, D. Timothy , Bouras, Emmanouil , Brenner, Hermann , Buchanan, Daniel D. , Campbell, Peter T. , Chan, Andrew T. , Chang‐Claude, Jenny , Conti, David V. , Devall, Matthew A M , Dimou, Niki , Gunter, Marc J. , Harrison, Tabitha A. , Hoffmeister, Michael , Hsu, Li , Keku, Temitope O , Lewinger, Juan Pablo , Lynch, Brigid M , Marchand, Loı̈c Le , Murphy, Neil , Ogino, Shuji , Ose, Jennifer , Palmer, Julie R. , Pardamean, Bens , Pellatt, Andrew J. , Platz, Elizabeth A. , Potter, John D. , Rennert, Gad , Ruiz-Narvaez, Edward , Sakoda, Lori C. , Schoen, Robert E., Shcherbina, Anna, Stern, Mariana Carla , Su, Yu-Ru , Thomas, Claire E. , Tian, Yu , Tsilidis, Konstantinos K. , Um, Caroline Y. , Guelpen, Bethany Van , Wang, Jun, White, Emily , Wolk, Alicja , Peters, Ulrike, Gauderman, W. James
No container title available | September 2, 2025 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Background Physical activity (PA) 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–PA interaction analysis. Methods Using logistic regression and two-step and joint tests, we analyzed interactions between common genetic variants across the genome and PA in relation to CRC risk. Self-reported PA levels were categorized as active (≥ 8.75 MET-h/wk) vs. inactive (< 8.75 MET-h/wk) and as study- and sex-specific quartiles of activity. Results PA had an overall protective effect on CRC (OR [active vs. inactive] = 0.85; 95%CI = 0.81–0.90). The two-step GxE method identified an interaction between rs4779584, an intergenic variant near the GREM1 and SCG5 genes, and PA 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 PA–CRC association among CT or TT carriers. When PA was modeled as quartiles, the 1-d.f. GxE test identified that rs56906466, an intergenic variant near the KCNG1 gene, modified the association between PA and CRC (p-interaction = 3.5×10 − 8 ). Stratification at this locus showed that increase in PA (highest vs. lowest quartile) was associated with a lower CRC risk solely among TT carriers (OR = 0.77; 95%CI = 0.72–0.82). Conclusions In summary, we identified two genetic variants that modified the association between PA 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 associated with the protective influence of PA on colorectal carcinogenesis.
Body mass index at birth and early life and colorectal cancer: A two‐sample Mendelian randomization analysis in European and East Asian genetic similarity populations
Papadimitriou, Nikos , Jenab, Mazda, Moreno, Victor, Platz, Elizabeth A., Duijnhoven, Fränzel J.B. van , Pai, Rish K. , Phipps, Amanda I. , Peters, Ulrike , Hughes, David J , Papadimitriou, Nikos , Murphy, Neil , Chen, Zhishan , Brenner, Hermann , Kweon, Sun-Seog , Marchand, Loı̈c Le , Platz, Elizabeth A. , Cheng, Iona C. , Zheng, Wei , Hughes, David J.
Pediatric Obesity | November 26, 2024 | Volume: 20 | Issue: 1 | Pages: No page available
SummaryBackgroundVarying obesogenic inherited predisposition in early to later life may differentially impact colorectal cancer (CRC) development. Previous Mendelian randomization (MR) studies, conducted in populations of European genetic similarity, have not observed any significant associations between early life body weight with CRC risk. However, it remains unclear whether body mass index (BMI) at different early lifetime points is causally related with CRC risk in both Europeans and East Asian populations.ObjectivesWe conducted a two‐sample MR study to investigate potential causal relationships between genetically predicted BMI during early life (birth to 8 years old) and at specific periods (birth, transient, early rise and late rise) and CRC risk.MethodsSummary data were obtained from genome‐wide association study (GWAS) of BMI in 28 681 children from the Norwegian Mother, Father and Child Cohort Study (MoBa) study and applied to CRC GWAS data from European and East Asian descent populations (102 893 cases and 485 083 non‐cases).ResultsThere were no significant associations observed between early life BMI and CRC risk in European or East Asian populations. The effect estimates were similar in European studies (odds ratio [OR] per a 1‐standard deviation [SD] increase: 1.01, 95% confidence interval [CI]: 0.95, 1.07) and in East Asians (OR per a 1‐SD increase: 1.02, 95% CI: 0.91, 1.14). Similar nonsignificant associations were found between time of BMI measurement during childhood and cancer‐site‐specific analyses.ConclusionsWe found little evidence of any associations between early life adiposity on later life CRC risk.