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153. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author

Turcot, Valérie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G. D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C. Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Gonçalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D’Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I. W., Groot, Mark C. H., Mutsert, Renée, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Jörgen, Grant, Struan F. A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Håkan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jørgensen, Marit E., Jørgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, René S., Kähönen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltán, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimäki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian’an, Lubitz, Steven A., Lyytikäinen, Leo-Pekka, Männistö, Satu, Marenne, Gaëlle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Müller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njølstad, Pål R., Nordestgaard, Børge G., Nyholt, Dale R., O’Connel, Jeffrey R., O’Donoghue, Michelle L., Loohuis, Loes M. Olde, Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R. B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renström, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H.-H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, André G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Edwards, Digna R. Velez, Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Völker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhao, Wei, Zhou, Wei, Zondervan, Krina T, CHD Exome+ Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, EPIC InterAct Consortium, INTERVAL Study, ReproGen Consortium, T2D-Genes Consortium, The MAGIC Investigators, Understanding Society Scientific Group, Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., and Loos, Ruth J. F.

Published
2019
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155. Genetically proxied glucose-lowering drug target perturbation and risk of cancer: a Mendelian randomisation analysis.

Author

Yarmolinsky, James, Bouras, Emmanouil, Constantinescu, Andrei, Burrows, Kimberley, Bull, Caroline J., Vincent, Emma E., Martin, Richard M., Dimopoulou, Olympia, Lewis, Sarah J., Moreno, Victor, Vujkovic, Marijana, Chang, Kyong-Mi, Voight, Benjamin F., Tsao, Philip S., Gunter, Marc J., Hampe, Jochen, Pellatt, Andrew J., Pharoah, Paul D. P., Schoen, Robert E., and Gallinger, Steven

Abstract

Aims/hypothesis: Epidemiological studies have generated conflicting findings on the relationship between glucose-lowering medication use and cancer risk. Naturally occurring variation in genes encoding glucose-lowering drug targets can be used to investigate the effect of their pharmacological perturbation on cancer risk. Methods: We developed genetic instruments for three glucose-lowering drug targets (peroxisome proliferator activated receptor γ [PPARG]; sulfonylurea receptor 1 [ATP binding cassette subfamily C member 8 (ABCC8)]; glucagon-like peptide 1 receptor [GLP1R]) using summary genetic association data from a genome-wide association study of type 2 diabetes in 148,726 cases and 965,732 controls in the Million Veteran Program. Genetic instruments were constructed using cis-acting genome-wide significant (p<5×10−8) SNPs permitted to be in weak linkage disequilibrium (r2<0.20). Summary genetic association estimates for these SNPs were obtained from genome-wide association study (GWAS) consortia for the following cancers: breast (122,977 cases, 105,974 controls); colorectal (58,221 cases, 67,694 controls); prostate (79,148 cases, 61,106 controls); and overall (i.e. site-combined) cancer (27,483 cases, 372,016 controls). Inverse-variance weighted random-effects models adjusting for linkage disequilibrium were employed to estimate causal associations between genetically proxied drug target perturbation and cancer risk. Co-localisation analysis was employed to examine robustness of findings to violations of Mendelian randomisation (MR) assumptions. A Bonferroni correction was employed as a heuristic to define associations from MR analyses as 'strong' and 'weak' evidence. Results: In MR analysis, genetically proxied PPARG perturbation was weakly associated with higher risk of prostate cancer (for PPARG perturbation equivalent to a 1 unit decrease in inverse rank normal transformed HbA1c: OR 1.75 [95% CI 1.07, 2.85], p=0.02). In histological subtype-stratified analyses, genetically proxied PPARG perturbation was weakly associated with lower risk of oestrogen receptor-positive breast cancer (OR 0.57 [95% CI 0.38, 0.85], p=6.45×10−3). In co-localisation analysis, however, there was little evidence of shared causal variants for type 2 diabetes liability and cancer endpoints in the PPARG locus, although these analyses were likely underpowered. There was little evidence to support associations between genetically proxied PPARG perturbation and colorectal or overall cancer risk or between genetically proxied ABCC8 or GLP1R perturbation with risk across cancer endpoints. Conclusions/interpretation: Our drug target MR analyses did not find consistent evidence to support an association of genetically proxied PPARG, ABCC8 or GLP1R perturbation with breast, colorectal, prostate or overall cancer risk. Further evaluation of these drug targets using alternative molecular epidemiological approaches may help to further corroborate the findings presented in this analysis. Data availability: Summary genetic association data for select cancer endpoints were obtained from the public domain: breast cancer (https://bcac.ccge.medschl.cam.ac.uk/bcacdata/); and overall prostate cancer (http://practical.icr.ac.uk/blog/). Summary genetic association data for colorectal cancer can be accessed by contacting GECCO (kafdem at fredhutch.org). Summary genetic association data on advanced prostate cancer can be accessed by contacting PRACTICAL (practical at icr.ac.uk). Summary genetic association data on type 2 diabetes from Vujkovic et al (Nat Genet, 2020) can be accessed through dbGAP under accession number phs001672.v3.p1 (pha004945.1 refers to the European-specific summary statistics). UK Biobank data can be accessed by registering with UK Biobank and completing the registration form in the Access Management System (AMS) (https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access). [ABSTRACT FROM AUTHOR]

Published
2023
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156. Low-Carbohydrate Diet Score and the Risk of Colorectal Cancer: Findings from the Singapore Chinese Health Study.

Author

Yi-Chuan Yu, Paragomi, Pedram, Aizhen Jin, Renwei Wang, Schoen, Robert E., Woon-Puay Koh, Jian-Min Yuan, and Luu, Hung N.

Abstract

Background: Colorectal cancer is common cancer with a high mortality rate. Low-carbohydrate diet (LCD) score holistically evaluates the LCD pattern from carbohydrate, protein, and fat intake. Epidemiologic data of LCD-colorectal cancer association are sparse. Methods: We evaluated the associations between LCD (i.e., total, animal- and plant-based) and colorectal cancer risk in the Singapore Chinese Health Study, a population-based prospective cohort study including 61,321 Chinese in Singapore who were 45 to 74 years old at baseline. Cox proportional hazard regression model was used to determine the HRs and respective 95% confidence intervals (CI) for colorectal cancer associated with LCD after adjusting for potential confounders, including age, sex, BMI, physical activity, family history of colorectal cancer, etc. Results: After an average of 19.5 years of follow-up, 2,520 participants developed colorectal cancer (1,608 colon cancer and 912 rectal cancer). Overall, the association between total or plant-based LCD scores with the risk of colorectal, colon, or rectal cancer was null (all Ptrend = 0.28). The animal-based LCD was modestly associated with colon cancer risk (Ptrend = 0.02), but not with rectal cancer. Compared with the lowest quartile, HRs (95% CIs) of colon cancer for quartiles 2, 3, and 4 of animal-based LCD were 1.12 (0.98-1.29), 1.27 (1.10-1.46), and 1.14 (0.99-1.31), respectively. Conclusions: A low-level carbohydrate diet with a high level of animal protein and fat was associated with a moderate increase in the risk of colon cancer among Chinese Singaporeans. Impact: High consumption of animal protein/fat and low consumption of carbohydrates may increase colon cancer risk. [ABSTRACT FROM AUTHOR]

Published
2023
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158. Abstract 1930: Unsupervised sub-cellular segmentation of complex tissue and cell samples using highly multiplexed imaging-derived a priori knowledge

Author

Kochetov, Bogdan, primary, Bell, Phoenix D., additional, Raphael, Rebecca, additional, Raymond, Benjamin J., additional, Leibowitz, Brian J., additional, Tong, Jingshan, additional, Diergaarde, Brenda, additional, Yu, Jian, additional, Pai, Reetesh K., additional, Schoen, Robert E., additional, Zhang, Lin, additional, Singhi, Aatur, additional, and Uttam, Shikhar, additional

Published
2022
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160. Identifying colorectal cancer caused by biallelic MUTYH pathogenic variants using tumor mutational signatures

Author

Georgeson, Peter, primary, Harrison, Tabitha A., additional, Pope, Bernard J., additional, Zaidi, Syed H., additional, Qu, Conghui, additional, Steinfelder, Robert S., additional, Lin, Yi, additional, Joo, Jihoon E., additional, Mahmood, Khalid, additional, Clendenning, Mark, additional, Walker, Romy, additional, Amitay, Efrat L., additional, Berndt, Sonja I., additional, Brenner, Hermann, additional, Campbell, Peter T., additional, Cao, Yin, additional, Chan, Andrew T., additional, Chang-Claude, Jenny, additional, Doheny, Kimberly F., additional, Drew, David A., additional, Figueiredo, Jane C., additional, French, Amy J., additional, Gallinger, Steven, additional, Giannakis, Marios, additional, Giles, Graham G., additional, Gsur, Andrea, additional, Gunter, Marc J., additional, Hoffmeister, Michael, additional, Hsu, Li, additional, Huang, Wen-Yi, additional, Limburg, Paul, additional, Manson, JoAnn E., additional, Moreno, Victor, additional, Nassir, Rami, additional, Nowak, Jonathan A., additional, Obón-Santacana, Mireia, additional, Ogino, Shuji, additional, Phipps, Amanda I., additional, Potter, John D., additional, Schoen, Robert E., additional, Sun, Wei, additional, Toland, Amanda E., additional, Trinh, Quang M., additional, Ugai, Tomotaka, additional, Macrae, Finlay A., additional, Rosty, Christophe, additional, Hudson, Thomas J., additional, Jenkins, Mark A., additional, Thibodeau, Stephen N., additional, Winship, Ingrid M., additional, Peters, Ulrike, additional, and Buchanan, Daniel D., additional

Published
2022
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161. Five- or 10-year colonoscopy for 1-2 non-advanced adenomatous polyps (FORTE) NRG-CC005 study: A randomized phase III non-inferiority trial comparing colorectal cancer incidence in participants with 1-2 non-advanced adenomas randomized to a 5- and 10-year surveillance colonoscopy exam schedule versus a 10-year surveillance colonoscopy exam schedule.

Author

Schoen, Robert E, primary, Bandos, Hanna, additional, Corley, Douglas, additional, Dueker, Jeff, additional, Yothers, Greg, additional, Bai, Jinbing, additional, Huh, Warner King, additional, Bauman, Julie E., additional, Walker, Joan L., additional, Bruner, Deborah, additional, and Kachnic, Lisa A., additional

Published
2022
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163. Genome-Wide Interaction Analysis of Genetic Variants With Menopausal Hormone Therapy for Colorectal Cancer Risk

Author

Tian, Yu, Kim, Andre E, Bien, Stephanie A, Lin, Yi, Qu, Conghui, Harrison, Tabitha A, Carreras-Torres, Robert, Díez-Obrero, Virginia, Dimou, Niki, Drew, David A, Hidaka, Akihisa, Huyghe, Jeroen R, Jordahl, Kristina M, Morrison, John, Murphy, Neil, Obón-Santacana, Mireia, Ulrich, Cornelia M, Ose, Jennifer, Peoples, Anita R, Ruiz-Narvaez, Edward A, Shcherbina, Anna, Stern, Mariana C, Su, Yu-Ru, van Duijnhoven, Franzel J B, Arndt, Volker, Baurley, James W, Berndt, Sonja I, Bishop, D Timothy, Brenner, Hermann, Buchanan, Daniel D, Chan, Andrew T, Figueiredo, Jane C, Gallinger, Steven, Gruber, Stephen B, Harlid, Sophia, Hoffmeister, Michael, Jenkins, Mark A, Joshi, Amit D, Keku, Temitope O, Larsson, Susanna C., Le Marchand, Loic, Li, Li, Giles, Graham G, Milne, Roger L, Nan, Hongmei, Nassir, Rami, Ogino, Shuji, Budiarto, Arif, Platz, Elizabeth A, Potter, John D, Prentice, Ross L, Rennert, Gad, Sakoda, Lori C, Schoen, Robert E, Slattery, Martha L, Thibodeau, Stephen N, Van Guelpen, Bethany, Visvanathan, Kala, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Campbell, Peter T, Casey, Graham, Conti, David V, Gunter, Marc J, Kundaje, Anshul, Lewinger, Juan Pablo, Moreno, Victor, Newcomb, Polly A, Pardamean, Bens, Thomas, Duncan C, Tsilidis, Konstantinos K, Peters, Ulrike, Gauderman, W James, Hsu, Li, Chang-Claude, Jenny, Tian, Yu, Kim, Andre E, Bien, Stephanie A, Lin, Yi, Qu, Conghui, Harrison, Tabitha A, Carreras-Torres, Robert, Díez-Obrero, Virginia, Dimou, Niki, Drew, David A, Hidaka, Akihisa, Huyghe, Jeroen R, Jordahl, Kristina M, Morrison, John, Murphy, Neil, Obón-Santacana, Mireia, Ulrich, Cornelia M, Ose, Jennifer, Peoples, Anita R, Ruiz-Narvaez, Edward A, Shcherbina, Anna, Stern, Mariana C, Su, Yu-Ru, van Duijnhoven, Franzel J B, Arndt, Volker, Baurley, James W, Berndt, Sonja I, Bishop, D Timothy, Brenner, Hermann, Buchanan, Daniel D, Chan, Andrew T, Figueiredo, Jane C, Gallinger, Steven, Gruber, Stephen B, Harlid, Sophia, Hoffmeister, Michael, Jenkins, Mark A, Joshi, Amit D, Keku, Temitope O, Larsson, Susanna C., Le Marchand, Loic, Li, Li, Giles, Graham G, Milne, Roger L, Nan, Hongmei, Nassir, Rami, Ogino, Shuji, Budiarto, Arif, Platz, Elizabeth A, Potter, John D, Prentice, Ross L, Rennert, Gad, Sakoda, Lori C, Schoen, Robert E, Slattery, Martha L, Thibodeau, Stephen N, Van Guelpen, Bethany, Visvanathan, Kala, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Campbell, Peter T, Casey, Graham, Conti, David V, Gunter, Marc J, Kundaje, Anshul, Lewinger, Juan Pablo, Moreno, Victor, Newcomb, Polly A, Pardamean, Bens, Thomas, Duncan C, Tsilidis, Konstantinos K, Peters, Ulrike, Gauderman, W James, Hsu, Li, and Chang-Claude, Jenny

Abstract

BACKGROUND: The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. METHODS: We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2- or 3-degree-of-freedom joint test. A set-based score test was applied for rare genetic variants. RESULTS: The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P < 1.2 × 10-4). CONCLUSION: Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.

Published
2022
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164. Large-scale Integrated Analysis of Genetics and Metabolomic Data Reveals Potential Links Between Lipids and Colorectal Cancer Risk

Author

Shu, Xiang, Chen, Zhishan, Long, Jirong, Guo, Xingyi, Yang, Yaohua, Qu, Conghui, Ahn, Yoon-Ok, Cai, Qiuyin, Casey, Graham, Gruber, Stephen B., Huyghe, Jeroen R., Jee, Sun Ha, Jenkins, Mark A., Jia, Wei-Hua, Jung, Keum Ji, Kamatani, Yoichiro, Kim, Dong-Hyun, Kim, Jeongseon, Kweon, Sun-Seog, Le Marchand, Loic, Matsuda, Koichi, Matsuo, Keitaro, Newcomb, Polly A., Oh, Jae Hwan, Ose, Jennifer, Oze, Isao, Pai, Rish K., Pan, Zhi-Zhong, Pharoah, Paul D.P., Playdon, Mary C., Ren, Ze-Fang, Schoen, Robert E., Shin, Aesun, Shin, Min-Ho, Shu, Xiao-Ou, Sun, Xiaohui, Tangen, Catherine M., Tanikawa, Chizu, Ulrich, Cornelia M., van Duijnhoven, Franzel J.B., van Guelpen, Bethany, Wolk, Alicja, Woods, Michael O., Wu, Anna H., Peters, Ulrike, Zheng, Wei, Shu, Xiang, Chen, Zhishan, Long, Jirong, Guo, Xingyi, Yang, Yaohua, Qu, Conghui, Ahn, Yoon-Ok, Cai, Qiuyin, Casey, Graham, Gruber, Stephen B., Huyghe, Jeroen R., Jee, Sun Ha, Jenkins, Mark A., Jia, Wei-Hua, Jung, Keum Ji, Kamatani, Yoichiro, Kim, Dong-Hyun, Kim, Jeongseon, Kweon, Sun-Seog, Le Marchand, Loic, Matsuda, Koichi, Matsuo, Keitaro, Newcomb, Polly A., Oh, Jae Hwan, Ose, Jennifer, Oze, Isao, Pai, Rish K., Pan, Zhi-Zhong, Pharoah, Paul D.P., Playdon, Mary C., Ren, Ze-Fang, Schoen, Robert E., Shin, Aesun, Shin, Min-Ho, Shu, Xiao-Ou, Sun, Xiaohui, Tangen, Catherine M., Tanikawa, Chizu, Ulrich, Cornelia M., van Duijnhoven, Franzel J.B., van Guelpen, Bethany, Wolk, Alicja, Woods, Michael O., Wu, Anna H., Peters, Ulrike, and Zheng, Wei

Abstract

Background: The etiology of colorectal cancer is not fully understood. Methods: Using genetic variants and metabolomics data including 217 metabolites from the Framingham Heart Study (n = 1,357), we built genetic prediction models for circulating metabolites. Models with prediction R2 > 0.01 (Nmetabolite = 58) were applied to predict levels of metabolites in two large consortia with a combined sample size of approximately 46,300 cases and 59,200 controls of European and approximately 21,700 cases and 47,400 controls of East Asian (EA) descent. Genetically predicted levels of metabolites were evaluated for their associations with colorectal cancer risk in logistic regressions within each racial group, after which the results were combined by meta-analysis. Results: Of the 58 metabolites tested, 24 metabolites were significantly associated with colorectal cancer risk [Benjamini-Hochberg FDR (BH-FDR) < 0.05] in the European population (ORs ranged from 0.91 to 1.06; P values ranged from 0.02 to 6.4 × 10-8). Twenty one of the 24 associations were replicated in the EA population (ORs ranged from 0.26 to 1.69, BH-FDR < 0.05). In addition, the genetically predicted levels of C16:0 cholesteryl ester was significantly associated with colorectal cancer risk in the EA population only (OREA: 1.94, 95% CI, 1.60−2.36, P = 2.6 × 10-11; OREUR: 1.01, 95% CI, 0.99−1.04, P = 0.3). Nineteen of the 25 metabolites were glycerophospholipids and triacylglycerols (TAG). Eighteen associations exhibited significant heterogeneity between the two racial groups (PEUR-EA-Het < 0.005), which were more strongly associated in the EA population. This integrative study suggested a potential role of lipids, especially certain glycerophospholipids and TAGs, in the etiology of colorectal cancer. Conclusions: This study identified potential novel risk biomarkers for colorectal cancer by integrating genetics and circulating metabolomics data. Impact: The identified metabolites could be developed

Published
2022
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167. A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1

Author

Lemire, Mathieu, Qu, Conghui, Loo, Lenora W. M., Zaidi, Syed H. E., Wang, Hansong, Berndt, Sonja I., Bézieau, Stéphane, Brenner, Hermann, Campbell, Peter T., Chan, Andrew T., Chang-Claude, Jenny, Du, Mengmeng, Edlund, Christopher K., Gallinger, Steven, Haile, Robert W., Harrison, Tabitha A., Hoffmeister, Michael, Hopper, John L., Hou, Lifang, Hsu, Li, Jacobs, Eric J., Jenkins, Mark A., Jeon, Jihyoun, Küry, Sébastien, Li, Li, Lindor, Noralane M., Newcomb, Polly A., Potter, John D., Rennert, Gad, Rudolph, Anja, Schoen, Robert E., Schumacher, Fredrick R., Seminara, Daniela, Severi, Gianluca, Slattery, Martha L., White, Emily, Woods, Michael O., Cotterchio, Michelle, Le Marchand, Loïc, Casey, Graham, Gruber, Stephen B., Peters, Ulrike, and Hudson, Thomas J.

Published
2015
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172. Genome-Wide Interaction Analysis of Genetic Variants With Menopausal Hormone Therapy for Colorectal Cancer Risk

Author

Tian, Yu, primary, Kim, Andre E, additional, Bien, Stephanie A, additional, Lin, Yi, additional, Qu, Conghui, additional, Harrison, Tabitha A, additional, Carreras-Torres, Robert, additional, Díez-Obrero, Virginia, additional, Dimou, Niki, additional, Drew, David A, additional, Hidaka, Akihisa, additional, Huyghe, Jeroen R, additional, Jordahl, Kristina M, additional, Morrison, John, additional, Murphy, Neil, additional, Obón-Santacana, Mireia, additional, Ulrich, Cornelia M, additional, Ose, Jennifer, additional, Peoples, Anita R, additional, Ruiz-Narvaez, Edward A, additional, Shcherbina, Anna, additional, Stern, Mariana C, additional, Su, Yu-Ru, additional, van Duijnhoven, Franzel J B, additional, Arndt, Volker, additional, Baurley, James W, additional, Berndt, Sonja I, additional, Bishop, D Timothy, additional, Brenner, Hermann, additional, Buchanan, Daniel D, additional, Chan, Andrew T, additional, Figueiredo, Jane C, additional, Gallinger, Steven, additional, Gruber, Stephen B, additional, Harlid, Sophia, additional, Hoffmeister, Michael, additional, Jenkins, Mark A, additional, Joshi, Amit D, additional, Keku, Temitope O, additional, Larsson, Susanna C, additional, Le Marchand, Loic, additional, Li, Li, additional, Giles, Graham G, additional, Milne, Roger L, additional, Nan, Hongmei, additional, Nassir, Rami, additional, Ogino, Shuji, additional, Budiarto, Arif, additional, Platz, Elizabeth A, additional, Potter, John D, additional, Prentice, Ross L, additional, Rennert, Gad, additional, Sakoda, Lori C, additional, Schoen, Robert E, additional, Slattery, Martha L, additional, Thibodeau, Stephen N, additional, Van Guelpen, Bethany, additional, Visvanathan, Kala, additional, White, Emily, additional, Wolk, Alicja, additional, Woods, Michael O, additional, Wu, Anna H, additional, Campbell, Peter T, additional, Casey, Graham, additional, Conti, David V, additional, Gunter, Marc J, additional, Kundaje, Anshul, additional, Lewinger, Juan Pablo, additional, Moreno, Victor, additional, Newcomb, Polly A, additional, Pardamean, Bens, additional, Thomas, Duncan C, additional, Tsilidis, Konstantinos K, additional, Peters, Ulrike, additional, Gauderman, W James, additional, Hsu, Li, additional, and Chang-Claude, Jenny, additional

Published
2022
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173. 785: CLINICAL AND GENOMIC CHARACTERIZATION OF INTERVAL COLORECTAL CANCER IN THREE PROSPECTIVE COHORTS

Author

Yang, Keming, primary, Cao, Yin, additional, Liu, Yang, additional, Gurjao, Carino, additional, Guo, Chuan-Guo, additional, Lo, Chun-Han, additional, Zong, Xiaoyu, additional, Drew, David A., additional, Geraghty, Connor M., additional, Prezioso, Elizabeth, additional, Moore, Matthew, additional, Williams, Craig R., additional, Riley, Tom, additional, Saul, Melissa, additional, Diergaarde, Brenda, additional, Ogino, Shuji, additional, Giannakis, Marios, additional, Bass, Adam, additional, Schoen, Robert E., additional, and Chan, Andrew, additional

Published
2022
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175. Large-scale integrated analysis of genetics and metabolomic data reveals potential links between lipids and colorectal cancer risk

Author

Shu, Xiang, primary, Chen, Zhishan, additional, Long, Jirong, additional, Guo, Xingyi, additional, Yang, Yaohua, additional, Qu, Conghui, additional, Ahn, Yoon-Ok, additional, Cai, Qiuyin, additional, Casey, Graham, additional, Gruber, Stephen B., additional, Huyghe, Jeroen R., additional, Jee, Sun Ha, additional, Jenkins, Mark A., additional, Jia, Wei-Hua, additional, Jung, Keum Ji, additional, Kamatani, Yoichiro, additional, Kim, Dong-Hyun, additional, Kim, Jeongseon, additional, Kweon, Sun-Seog, additional, Le Marchand, Loic, additional, Matsuda, Koichi, additional, Matsuo, Keitaro, additional, Newcomb, Polly A., additional, Oh, Jae Hwan, additional, Ose, Jennifer, additional, Oze, Isao, additional, Pai, Rish K., additional, Pan, Zhi-Zhong, additional, Pharoah, Paul D P., additional, Playdon, Mary C., additional, Ren, Ze-Fang, additional, Schoen, Robert E., additional, Shin, Aesun, additional, Shin, Min-Ho, additional, Shu, Xiao-Ou, additional, Sun, Xiaohui, additional, Tangen, Catherine M., additional, Tanikawa, Chizu, additional, Ulrich, Cornelia M., additional, van Duijnhoven, Fränzel J B., additional, Van Guelpen, Bethany, additional, Wolk, Alicja, additional, Woods, Michael O., additional, Wu, Anna H., additional, Peters, Ulrike, additional, and Zheng, Wei, additional

Published
2022
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179. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author

Turcot, Valérie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G. D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C. Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Gonçalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Corominas Galbany, Jordi, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D’Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I. W., Groot, Mark C. H., Mutsert, Renée, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Jörgen, Grant, Struan F. A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Håkan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jørgensen, Marit E., Jørgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, René S., Kähönen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltán, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimäki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian’an, Lubitz, Steven A., Lyytikäinen, Leo-Pekka, Männistö, Satu, Marenne, Gaëlle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Müller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njølstad, Pål R., Nordestgaard, Børge G., Nyholt, Dale R., O’Connel, Jeffrey R., O’Donoghue, Michelle L., Olde Loohuis, Loes M., Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R. B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renström, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H.-H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, André G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Velez Edwards, Digna R., Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Völker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhao, Wei, Zhou, Wei, Zondervan, Krina T, Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., Loos, Ruth J. F., CHD Exome+ Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, EPIC InterAct Consortium, INTERVAL Study, ReproGen Consortium, T2D-Genes Consortium, The MAGIC Investigators, and Understanding Society Scientific Group

Published
2018
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182. Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region

Author

Jordahl, Kristina M., primary, Shcherbina, Anna, additional, Kim, Andre E., additional, Su, Yu-Ru, additional, Lin, Yi, additional, Wang, Jun, additional, Qu, Conghui, additional, Albanes, Demetrius, additional, Arndt, Volker, additional, Baurley, James W., additional, Berndt, Sonja I., additional, Bien, Stephanie A., additional, Bishop, D. Timothy, additional, Bouras, Emmanouil, additional, Brenner, Hermann, additional, Buchanan, Daniel D., additional, Budiarto, Arif, additional, Campbell, Peter T., additional, Carreras-Torres, Robert, additional, Casey, Graham, additional, Cenggoro, Tjeng Wawan, additional, Chan, Andrew T., additional, Conti, David V., additional, Dampier, Christopher H., additional, Devall, Matthew A., additional, Díez-Obrero, Virginia, additional, Dimou, Niki, additional, Drew, David A., additional, Figueiredo, Jane C., additional, Gallinger, Steven, additional, Giles, Graham G., additional, Gruber, Stephen B., additional, Gsur, Andrea, additional, Gunter, Marc J., additional, Hampel, Heather, additional, Harlid, Sophia, additional, Harrison, Tabitha A., additional, Hidaka, Akihisa, additional, Hoffmeister, Michael, additional, Huyghe, Jeroen R., additional, Jenkins, Mark A., additional, Joshi, Amit D., additional, Keku, Temitope O., additional, Larsson, Susanna C., additional, Le Marchand, Loic, additional, Lewinger, Juan Pablo, additional, Li, Li, additional, Mahesworo, Bharuno, additional, Moreno, Victor, additional, Morrison, John L., additional, Murphy, Neil, additional, Nan, Hongmei, additional, Nassir, Rami, additional, Newcomb, Polly A., additional, Obón-Santacana, Mireia, additional, Ogino, Shuji, additional, Ose, Jennifer, additional, Pai, Rish K., additional, Palmer, Julie R., additional, Papadimitriou, Nikos, additional, Pardamean, Bens, additional, Peoples, Anita R., additional, Pharoah, Paul D.P., additional, Platz, Elizabeth A., additional, Potter, John D., additional, Prentice, Ross L., additional, Rennert, Gad, additional, Ruiz-Narvaez, Edward, additional, Sakoda, Lori C., additional, Scacheri, Peter C., additional, Schmit, Stephanie L., additional, Schoen, Robert E., additional, Slattery, Martha L., additional, Stern, Mariana C., additional, Tangen, Catherine M., additional, Thibodeau, Stephen N., additional, Thomas, Duncan C., additional, Tian, Yu, additional, Tsilidis, Konstantinos K., additional, Ulrich, Cornelia M., additional, van Duijnhoven, Franzel J.B., additional, Van Guelpen, Bethany, additional, Visvanathan, Kala, additional, Vodicka, Pavel, additional, White, Emily, additional, Wolk, Alicja, additional, Woods, Michael O., additional, Wu, Anna H., additional, Zemlianskaia, Natalia, additional, Chang-Claude, Jenny, additional, Gauderman, W. James, additional, Hsu, Li, additional, Kundaje, Anshul, additional, and Peters, Ulrike, additional

Published
2022
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185. Genetic variants associated with circulating C‐reactive protein levels and colorectal cancer survival: Sex‐specific and lifestyle factors specific associations

Author

Huang, Yuhan, primary, Hua, Xinwei, additional, Labadie, Julia D., additional, Harrison, Tabitha A., additional, Dai, James Y., additional, Lindstrom, Sara, additional, Lin, Yi, additional, Berndt, Sonja I., additional, Buchanan, Daniel D., additional, Campbell, Peter T., additional, Casey, Graham, additional, Gallinger, Steven J., additional, Gunter, Marc J., additional, Hoffmeister, Michael, additional, Jenkins, Mark A., additional, Sakoda, Lori C., additional, Schoen, Robert E., additional, Diergaarde, Brenda, additional, Slattery, Martha L., additional, White, Emily, additional, Giles, Graham, additional, Brenner, Hermann, additional, Chang‐Claude, Jenny, additional, Joshi, Amit, additional, Ma, Wenjie, additional, Pai, Rish K., additional, Chan, Andrew T., additional, Peters, Ulrike, additional, and Newcomb, Polly A., additional

Published
2022
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187. Prevalence of intratumoral regulatory T cells expressing neuropilin-1 is associated with poorer outcomes in patients with cancer

Author

Chuckran, Christopher A., primary, Cillo, Anthony R., additional, Moskovitz, Jessica, additional, Overacre-Delgoffe, Abigail, additional, Somasundaram, Ashwin S., additional, Shan, Feng, additional, Magnon, Grant C., additional, Kunning, Sheryl R., additional, Abecassis, Irina, additional, Zureikat, Amer H., additional, Luketich, James, additional, Pennathur, Arjun, additional, Sembrat, John, additional, Rojas, Mauricio, additional, Merrick, Daniel T., additional, Taylor, Sarah E., additional, Orr, Brian, additional, Modugno, Francesmary, additional, Buckanovich, Ron, additional, Schoen, Robert E., additional, Kim, Seungwon, additional, Duvvuri, Umamaheswar, additional, Zeh, Herbert, additional, Edwards, Robert, additional, Kirkwood, John M., additional, Coffman, Lan, additional, Ferris, Robert L., additional, Bruno, Tullia C., additional, and Vignali, Dario A. A., additional

Published
2021
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188. Recommendations for a step-wise comparative approach to the evaluation of new screening tests for colorectal cancer

Author

Young, Graeme P., Senore, Carlo, Mandel, Jack S., Allison, James E., Atkin, Wendy S., Benamouzig, Robert, Bossuyt, Patrick M. M., Silva, Mahinda De, Guittet, Lydia, Halloran, Stephen P., Haug, Ulrike, Hoff, Geir, Itzkowitz, Steven H., Leja, Marcis, Levin, Bernard, Meijer, Gerrit A., OʼMorain, Colm A., Parry, Susan, Rabeneck, Linda, Rozen, Paul, Saito, Hiroshi, Schoen, Robert E., Seaman, Helen E., Steele, Robert J. C., Sung, Joseph J. Y., and Winawer, Sidney J.

Published
2016
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189. Targeting Myc-driven stress vulnerability in mutant KRAS colorectal cancer.

Author

Hang Ruan, Leibowitz, Brian J., Yingpeng Peng, Lin Shen, Lujia Chen, Kuang, Charlie, Schoen, Robert E., Xinghua Lu, Lin Zhang, and Jian Yu

Abstract

Mutant KRAS is a key driver in colorectal cancer (CRC) and promotes Myc translation and Myc-dependent stress adaptation and proliferation. Here, we report that the combination of two FDA-approved drugs Bortezomib and Everolimus (RAD001) (BR) is highly efficacious against mutant KRAS CRC cells. Mechanistically, the combination, not single agent, rapidly depletes Myc protein, not mRNA, and leads to GCN2- and p-eIF2α-dependent cell death through the activation of extrinsic and intrinsic apoptotic pathways. Cell death is selectively induced in mutant KRAS CRC cells with elevated basal Myc and p-eIF2α and is characterized by CHOP induction and transcriptional signatures in proteotoxicity, oxidative stress, metabolic inhibition, and immune activation. BR-induced p-GCN2/p-eIF2α elevation and cell death are strongly attenuated by MYC knockdown and enhanced by MYC overexpression. The BR combination is efficacious against mutant KRAS patient derived organoids (PDO) and xenografts (PDX) by inducing p-eIF2α/CHOP and cell death. Interestingly, an elevated four-gene (DDIT3, GADD45B, CRYBA4 and HSPA1L) stress signature is linked to shortened overall survival in CRC patients. These data support that Myc-dependent stress adaptation drives the progression of mutant KRAS CRC and serves as a therapeutic vulnerability, which can be targeted using dual translational inhibitors. [ABSTRACT FROM AUTHOR]

Published
2022
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193. Salicylic acid and risk of colorectal cancer: a two sample Mendelian randomization study

Author

Nounu, Aayah, primary, Richmond, Rebecca C, additional, Stewart, Isobel D, additional, Surendran, Praveen, additional, Wareham, Nicholas J., additional, Butterworth, Adam, additional, Weinstein, Stephanie J, additional, Albanes, Demetrius, additional, Baron, John A, additional, Hopper, John L, additional, Figueiredo, Jane C, additional, Newcomb, Polly A, additional, Lindor, Noralane M, additional, Casey, Graham, additional, Platz, Elizabeth A, additional, Marchand, Loïc Le, additional, Ulrich, Cornelia M, additional, Li, Christopher I, additional, van Duijnhoven, Fränzel JB, additional, Gsur, Andrea, additional, Campbell, Peter T, additional, Moreno, Víctor, additional, Vodicka, Pavel, additional, Vodickova, Ludmila, additional, Amitay, Efrat, additional, Alwers, Elizabeth, additional, Chang-Claude, Jenny, additional, Sakoda, Lori C, additional, Slattery, Martha L, additional, Schoen, Robert E, additional, Gunter, Marc J, additional, Castellví-Bel, Sergi, additional, Kim, Hyeong Rok, additional, Kweon, Sun-Seog, additional, Chan, Andrew T, additional, Li, Li, additional, Zheng, Wei, additional, Bishop, D Timothy, additional, Buchanan, Daniel D, additional, Giles, Graham G, additional, Gruber, Stephen B, additional, Rennert, Gad, additional, Stadler, Zsofia K, additional, Harrison, Tabitha A, additional, Lin, Yi, additional, Keku, Temitope O, additional, Woods, Michael O, additional, Schafmayer, Clemens, additional, Van Guelpen, Bethany, additional, Gallinger, Steven, additional, Hampel, Heather, additional, Berndt, Sonja I, additional, Pharoah, Paul D P, additional, Lindblom, Annika, additional, Wolk, Alicja, additional, Wu, Anna H, additional, White, Emily, additional, Peters, Ulrike, additional, Drew, David A, additional, Scherer, Dominique, additional, Bermejo, Justo Lorenzo, additional, Brenner, Hermann, additional, Hoffmeister, Michael, additional, Williams, Ann C, additional, and Relton, Caroline L, additional

Published
2021
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195. Genetic variants of adiponectin and risk of colorectal cancer

Author

Song, Mingyang, Gong, Jian, Giovannucci, Edward L., Berndt, Sonja I., Brenner, Hermann, Chang-Claude, Jenny, Curtis, Keith R., Harrison, Tabitha A., Hoffmeister, Michael, Hsu, Li, Jiao, Shuo, Le Marchand, Loic, Potter, John D., Schoen, Robert E., Seminara, Daniela, Slattery, Martha L., White, Emily, Wu, Kana, Ogino, Shuji, Fuchs, Charles S., Hunter, David J., Tworoger, Shelley S., Hu, Frank B., Rimm, Eric, Jensen, Majken, Peters, Ulrike, and Chan, Andrew T.

Published
2015
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197. Mendelian randomization study of height and risk of colorectal cancer

Author

Thrift, Aaron P, Gong, Jian, Peters, Ulrike, Chang-Claude, Jenny, Rudolph, Anja, Slattery, Martha L, Chan, Andrew T, Esko, Tonu, Wood, Andrew R, Yang, Jian, Vedantam, Sailaja, Gustafsson, Stefan, Pers, Tune H, Baron, John A, Bezieau, Stéphane, Küry, Sébastien, Ogino, Shuji, Berndt, Sonja I, Casey, Graham, Haile, Robert W, Du, Mengmeng, Harrison, Tabitha A, Thornquist, Mark, Duggan, David J, Le Marchand, Loic, Lemire, Mathieu, Lindor, Noralane M, Seminara, Daniela, Song, Mingyang, Thibodeau, Stephen N, Cotterchio, Michelle, Win, Aung Ko, Jenkins, Mark A, Hopper, John L, Ulrich, Cornelia M, Potter, John D, Newcomb, Polly A, Schoen, Robert E, Hoffmeister, Michael, Brenner, Hermann, White, Emily, Hsu, Li, and Campbell, Peter T

Published
2015
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198. Association of Aspirin and NSAID Use With Risk of Colorectal Cancer According to Genetic Variants

Author

Nan, Hongmei, Hutter, Carolyn M., Lin, Yi, Jacobs, Eric J., Ulrich, Cornelia M., White, Emily, Baron, John A., Berndt, Sonja I., Brenner, Hermann, Butterbach, Katja, Caan, Bette J., Campbell, Peter T., Carlson, Christopher S., Casey, Graham, Chang-Claude, Jenny, Chanock, Stephen J., Cotterchio, Michelle, Duggan, David, Figueiredo, Jane C., Fuchs, Charles S., Giovannucci, Edward L., Gong, Jian, Haile, Robert W., Harrison, Tabitha A., Hayes, Richard B., Hoffmeister, Michael, Hopper, John L., Hudson, Thomas J., Jenkins, Mark A., Jiao, Shuo, Lindor, Noralane M., Lemire, Mathieu, Le Marchand, Loic, Newcomb, Polly A., Ogino, Shuji, Pflugeisen, Bethann M., Potter, John D., Qu, Conghui, Rosse, Stephanie A., Rudolph, Anja, Schoen, Robert E., Schumacher, Fredrick R., Seminara, Daniela, Slattery, Martha L., Thibodeau, Stephen N., Thomas, Fridtjof, Thornquist, Mark, Warnick, Greg S., Zanke, Brent W., Gauderman, W. James, Peters, Ulrike, Hsu, Li, and Chan, Andrew T.

Published
2015
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