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636 results on '"Martin, Richard M"'

1. Optical bounds on many-electron localization

Author

Souza, Ivo, Martin, Richard M., and Stengel, Massimiliano

Subjects
Condensed Matter - Materials Science
Abstract

We establish rigorous inequalities between different electronic properties linked to optical sum rules, and organize them into weak and strong bounds on three characteristic properties of insulators: electron localization length $\ell$ (the quantum fluctuations in polarization), electric susceptibility $\chi$, and optical gap $E_{\rm G}$. All-electron and valence-only versions of the bounds are given, and the latter are found to be more informative. The bounds on $\ell$ are particularly interesting, as they provide reasonably tight estimates for an ellusive ground-state property -- the average localization length of valence electrons -- from tabulated experimental data: electron density, high-frequency dielectric constant, and optical gap. The localization lengths estimated in this way for several materials follow simple chemical trends, especially for the alkali halides. We also illustrate our findings via analytically solvable harmonic oscillator models, which reveal an intriguing connection to the physics of long-ranged van der Waals forces.

Published
2024

2. Spin-resolved electronic structure of ferromagnetic triple-layered ruthenate Sr$_4$Ru$_3$O$_{10}$

Author

Ngabonziza, Prosper, Denlinger, Jonathan D., Fedorov, Alexei V., Cao, Gang, Allen, J. W., Gebreyesus, G., and Martin, Richard M.

Subjects
Condensed Matter - Strongly Correlated Electrons, Condensed Matter - Other Condensed Matter
Abstract

High-resolution angle- and spin-resolved photoemission spectroscopy reveals new features of the electronic structure of the ferromagnetic triple-layered ruthenate Sr$_4$Ru$_3$O$_{10}$. There are narrow spectral peaks $\sim$30 meV below the Fermi-level in two regions of the Brillouin zone: a hole-like band at the zone-center and a saddle-point van Hove singularity at the zone edge. Below T$_c$ each feature is almost completely spin-polarized, with opposite sign polarization and with strong Kondo-coherence-like temperature-dependent spectral weight variation suggestive of strong Hund's metal correlations. In addition, there are distinct Fermi surfaces for wide electron-like minority spin bands around the zone center and narrow hole-like majority spin Fermi surface contours around the zone corners. The origin of these features is in general agreement with density functional calculations, if they are shifted to reduce the exchange splitting, and scaled to take into account effects of correlation. Furthermore, the deduced narrow band origins from the tri-layer splitting of $d_{xz/yz}$ orbitals implies a layer-specific spin-polarization contribution from the narrow bands. Over a larger energy range, net spin-majority polarization of incoherent Ru $d$-bands is observed to extend down to the top of the oxygen bands, where additional narrow oxygen bands contribute to the magnetism with spin-minority polarization., Comment: 11 pages, 5 figures plus supplement 8 pages, 4 figures

Published
2023

3. Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants

Author

Wang, Anqi, Shen, Jiayi, Rodriguez, Alex A., Saunders, Edward J., Chen, Fei, Janivara, Rohini, Darst, Burcu F., Sheng, Xin, Xu, Yili, Chou, Alisha J., Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N., Plym, Anna, Sahimi, Ali, Hoffman, Thomas J., Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Laisk, Triin, Figuerêdo, Jéssica, Muir, Kenneth, Ito, Shuji, Liu, Xiaoxi, Uchio, Yuji, Kubo, Michiaki, Kamatani, Yoichiro, Lophatananon, Artitaya, Wan, Peggy, Andrews, Caroline, Lori, Adriana, Choudhury, Parichoy P., Schleutker, Johanna, Tammela, Teuvo L. J., Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Rentsch, Christopher T., Cho, Kelly, Mcmahon, Benjamin H., Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Nordestgaard, Borge G., Nielsen, Sune F., Weischer, Maren, Bojesen, Stig E., Røder, Andreas, Stroomberg, Hein V., Batra, Jyotsna, Chambers, Suzanne, Horvath, Lisa, Clements, Judith A., Tilly, Wayne, Risbridger, Gail P., Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordstrom, Tobias, Pashayan, Nora, Dunning, Alison M., Ghoussaini, Maya, Travis, Ruth C., Key, Tim J., Riboli, Elio, Park, Jong Y., Sellers, Thomas A., Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie, Cook, Michael B., Mucci, Lorelei A., Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J., Penney, Kathryn L., Turman, Constance, Tangen, Catherine M., Goodman, Phyllis J., Thompson, Jr., Ian M., Hamilton, Robert J., Fleshner, Neil E., Finelli, Antonio, Parent, Marie-Élise, Stanford, Janet L., Ostrander, Elaine A., Koutros, Stella, Beane Freeman, Laura E., Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L., Hoover, Robert N., Machiela, Mitchell J., Sørensen, Karina Dalsgaard, Borre, Michael, Blot, William J., Zheng, Wei, Yeboah, Edward D., Mensah, James E., Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Wu, Yudong, Zhao, Shan-Chao, Sun, Zan, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., West, Catharine M. L., Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Luedeke, Manuel, Kibel, Adam S., Drake, Bettina F., Cussenot, Olivier, Cancel-Tassin, Geraldine, Menegaux, Florence, Truong, Thérèse, Koudou, Yves Akoli, John, Esther M., Grindedal, Eli Marie, Maehle, Lovise, Khaw, Kay-Tee, Ingles, Sue A., Stern, Mariana C., Vega, Ana, Gómez-Caamaño, Antonio, Fachal, Laura, Rosenstein, Barry S., Kerns, Sarah L., Ostrer, Harry, Teixeira, Manuel R., Paulo, Paula, Brandão, Andreia, Watya, Stephen, Lubwama, Alexander, Bensen, Jeannette T., Butler, Ebonee N., Mohler, James L., Taylor, Jack A., Kogevinas, Manolis, Dierssen-Sotos, Trinidad, Castaño-Vinyals, Gemma, Cannon-Albright, Lisa, Teerlink, Craig C., Huff, Chad D., Pilie, Patrick, Yu, Yao, Bohlender, Ryan J., Gu, Jian, Strom, Sara S., Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Kaneva, Radka, Slavov, Chavdar, Mitev, Vanio, Leach, Robin J., Brenner, Hermann, Chen, Xuechen, Holleczek, Bernd, Schöttker, Ben, Klein, Eric A., Hsing, Ann W., Kittles, Rick A., Murphy, Adam B., Logothetis, Christopher J., Kim, Jeri, Neuhausen, Susan L., Steele, Linda, Ding, Yuan Chun, Isaacs, William B., Nemesure, Barbara, Hennis, Anselm J. M., Carpten, John, Pandha, Hardev, Michael, Agnieszka, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Xu, Jianfeng, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Newcomb, Lisa F., Lin, Daniel W., Fowke, Jay H., Neslund-Dudas, Christine M., Rybicki, Benjamin A., Gamulin, Marija, Lessel, Davor, Kulis, Tomislav, Usmani, Nawaid, Abraham, Aswin, Singhal, Sandeep, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Bush, William S., Aldrich, Melinda C., Crawford, Dana C., Srivastava, Shiv, Cullen, Jennifer, Petrovics, Gyorgy, Casey, Graham, Wang, Ying, Tettey, Yao, Lachance, Joseph, Tang, Wei, Biritwum, Richard B., Adjei, Andrew A., Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Yamoah, Kosj, Govindasami, Koveela, Chokkalingam, Anand P., Keaton, Jacob M., Hellwege, Jacklyn N., Clark, Peter E., Jalloh, Mohamed, Gueye, Serigne M., Niang, Lamine, Ogunbiyi, Olufemi, Shittu, Olayiwola, Amodu, Olukemi, Adebiyi, Akindele O., Aisuodionoe-Shadrach, Oseremen I., Ajibola, Hafees O., Jamda, Mustapha A., Oluwole, Olabode P., Nwegbu, Maxwell, Adusei, Ben, Mante, Sunny, Darkwa-Abrahams, Afua, Diop, Halimatou, Gundell, Susan M., Roobol, Monique J., Jenster, Guido, van Schaik, Ron H. N., Hu, Jennifer J., Sanderson, Maureen, Kachuri, Linda, Varma, Rohit, McKean-Cowdin, Roberta, Torres, Mina, Preuss, Michael H., Loos, Ruth J. F., Zawistowski, Matthew, Zöllner, Sebastian, Lu, Zeyun, Van Den Eeden, Stephen K., Easton, Douglas F., Ambs, Stefan, Edwards, Todd L., Mägi, Reedik, Rebbeck, Timothy R., Fritsche, Lars, Chanock, Stephen J., Berndt, Sonja I., Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S., Gaziano, J. Michael, Justice, Amy C., Mancuso, Nick, Terao, Chikashi, Eeles, Rosalind A., Kote-Jarai, Zsofia, Madduri, Ravi K., Conti, David V., and Haiman, Christopher A.

Published
2023
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4. Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study

Author

Dixon-Suen, Suzanne C, Lewis, Sarah J, Martin, Richard M, English, Dallas R, Boyle, Terry, Giles, Graham G, Michailidou, Kyriaki, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Lush, Michael, Investigators, ABCTB, Ahearn, Thomas U, Ambrosone, Christine B, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Augustinsson, Annelie, Auvinen, Päivi, Freeman, Laura E Beane, Becher, Heiko, Beckmann, Matthias W, Behrens, Sabine, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Bonanni, Bernardo, Brenner, Hermann, Brüning, Thomas, Buys, Saundra S, Camp, Nicola J, Campa, Daniele, Canzian, Federico, Castelao, Jose E, Cessna, Melissa H, Chang-Claude, Jenny, Chanock, Stephen J, Clarke, Christine L, Conroy, Don M, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dörk, Thilo, Dwek, Miriam, Eccles, Diana M, Eliassen, A Heather, Engel, Christoph, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Fletcher, Olivia, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, García-Closas, Montserrat, García-Sáenz, José A, Goldberg, Mark S, Guénel, Pascal, Gündert, Melanie, Hahnen, Eric, Haiman, Christopher A, Häberle, Lothar, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hart, Steven N, Harvie, Michelle, Hillemanns, Peter, Hollestelle, Antoinette, Hooning, Maartje J, Hoppe, Reiner, Hopper, John, Howell, Anthony, Hunter, David J, Jakubowska, Anna, Janni, Wolfgang, John, Esther M, Jung, Audrey, Kaaks, Rudolf, Keeman, Renske, Kitahara, Cari M, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N, Kubelka-Sabit, Katerina, Kurian, Allison W, Lacey, James V, Lambrechts, Diether, Le Marchand, Loic, Lindblom, Annika, Loibl, Sibylle, Lubiński, Jan, Mannermaa, Arto, and Manoochehri, Mehdi

Subjects
Aging, Genetics, Breast Cancer, Clinical Research, Cancer, Prevention, Female, Humans, Breast Neoplasms, Exercise, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Risk Factors, Sedentary Behavior, Breast Cancer Association Consortium, Breast, Physical activity, Sedentary Behaviour, Engineering, Medical and Health Sciences, Education, Sport Sciences
Abstract

ObjectivesPhysical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.MethodsWe performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.ResultsGreater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).ConclusionOur study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.

Published
2022

5. The effect of SGLT2 inhibition on prostate cancer: Mendelian randomization and observational analysis using electronic healthcare and cohort data

Author

Zheng, Jie, Lu, Jieli, Qi, Jiying, Yang, Qian, Zhao, Huiling, Liu, Haoyu, Chen, Zhihe, Huang, Lanhui, Ye, Youqiong, Xu, Min, Xu, Yu, Wang, Tiange, Li, Mian, Zhao, Zhiyun, Zheng, Ruizhi, Wang, Shuangyuan, Lin, Hong, Hu, Chunyan, Ling Chui, Celine Sze, Au Yeung, Shiu Lun, Luo, Shan, Dimopoulou, Olympia, Dixon, Padraig, Harrison, Sean, Liu, Yi, Robinson, Jamie, Yarmolinsky, James, Haycock, Philip, Yuan, Jinqiu, Lewis, Sarah, Yuan, Zhongshang, Gaunt, Tom R., Smith, George Davey, Ning, Guang, Martin, Richard M., Cui, Bin, Wang, Weiqing, and Bi, Yufang

Published
2024
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6. Identifying proteomic risk factors for overall, aggressive, and early onset prostate cancer using Mendelian Randomisation and tumour spatial transcriptomics

Author

Desai, Trishna A., Hedman, Åsa K., Dimitriou, Marios, Koprulu, Mine, Figiel, Sandy, Yin, Wencheng, Johansson, Mattias, Watts, Eleanor L., Atkins, Joshua R., Sokolov, Aleksandr V., Schiöth, Helgi B., Gunter, Marc J., Tsilidis, Konstantinos K., Martin, Richard M., Pietzner, Maik, Langenberg, Claudia, Mills, Ian G., Lamb, Alastair D., Mälarstig, Anders, Key, Tim J., Travis, Ruth C., and Smith-Byrne, Karl

Published
2024
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7. 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., Gallinger, Steven, Jenkins, Mark A., Pai, Rish K., Gill, Dipender, and Tsilidis, Kostas K.

Published
2023
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8. Electronic Structure and Magnetism of the Triple-layered Ruthenate Sr$_{4}$Ru$_{3}$O$_{10}$

Author

Gebreyesus, G., Ngabonziza, Prosper, Nagura, Jonah, Seriani, Nicola, Akin-Ojo, Omololu, and Martin, Richard M.

Subjects
Condensed Matter - Strongly Correlated Electrons
Abstract

We report electronic band structure calculations for Sr$_{4}$Ru$_{3}$O$_{10}$ that displays both ferromagnetic and metamagnetic behavior. The density functional calculations find the ground state to be ferromagnetic in agreement with the experiment and we find that the inclusion of Coulomb Hubbard interaction U applied to the Ru 4d states has dramatic effects on the Fermi surface, which reveal the role of Coulomb interactions and correlated many-body physics. The minority spin bands are mainly empty with Fermi surfaces in the outer areas of the Brillouin zone away from the $\Gamma$ point with bands that disperse steeply upward. The majority spin bands are full or nearly fully occupied and form narrow bands near the Fermi energy around the $\Gamma$ point, which could be the electronic origin of the metamagnetism. The results are in qualitative agreement with recent angle resolved photoemission spectroscopy (ARPES) experiments and show the need for a combined theoretical study and experimental ARPES investigation with better energy resolution to reveal the nature of the narrow bands close to the Fermi-level, which is critical for understanding the exotic magnetic properties observed in this material.

Published
2021
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10. Body size and risk of colorectal cancer molecular defined subtypes and pathways: Mendelian randomization analyses

Author

Papadimitriou, Nikos, Qu, Conghui, Harrison, Tabitha A., Bever, Alaina M., Martin, Richard M., Tsilidis, Konstantinos K., Newcomb, Polly A., Thibodeau, Stephen N., Newton, Christina C., Um, Caroline Y., Obón-Santacana, Mireia, Moreno, Victor, Brenner, Hermann, Mandic, Marko, Chang-Claude, Jenny, Hoffmeister, Michael, Pellatt, Andrew J., Schoen, Robert E., Harlid, Sophia, Ogino, Shuji, Ugai, Tomotaka, Buchanan, Daniel D., Lynch, Brigid M., Gruber, Stephen B., Cao, Yin, Hsu, Li, Huyghe, Jeroen R., Lin, Yi, Steinfelder, Robert S., Sun, Wei, Van Guelpen, Bethany, Zaidi, Syed H., Toland, Amanda E., Berndt, Sonja I., Huang, Wen-Yi, Aglago, Elom K., Drew, David A., French, Amy J., Georgeson, Peter, Giannakis, Marios, Hullar, Meredith, Nowak, Johnathan A., Thomas, Claire E., Le Marchand, Loic, Cheng, Iona, Gallinger, Steven, Jenkins, Mark A., Gunter, Marc J., Campbell, Peter T., Peters, Ulrike, Song, Mingyang, Phipps, Amanda I., and Murphy, Neil

Published
2024
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11. Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis

Author

Landi, Maria Teresa, Stevens, Victoria, Wang, Ying, Albanes, Demetrios, Caporaso, Neil, Brennan, Paul, Amos, Christopher I., Shete, Sanjay, Hung, Rayjean J., Bickeböller, Heike, Risch, Angela, Houlston, Richard, Lam, Stephen, Tardon, Adonina, Chen, Chu, Bojesen, Stig E., Johansson, Mattias, Wichmann, H-Erich, Christiani, David, Rennert, Gadi, Arnold, Susanne, Field, John K., Le Marchand, Loic, Melander, Olle, Brunnström, Hans, Liu, Geoffrey, Andrew, Angeline, Kiemeney, Lambertus A., Shen, Hongbing, Zienolddiny, Shan, Grankvist, Kjell, Johansson, Mikael, Teare, M. Dawn, Hong, Yun-Chul, Yuan, Jian-Min, Lazarus, Philip, Schabath, Matthew B., Aldrich, Melinda C., Eeles, Rosalind A., Haiman, Christopher A., Kote-Jarai, Zsofia, Schumacher, Fredrick R., Benlloch, Sara, Al Olama, Ali Amin, Muir, Kenneth R., Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Chanock, Stephen, Tangen, Catherine M., Batra, Jyotsna, Clements, Judith A., Grönberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie J., Wolk, Alicja, West, Catharine M.L., Mucci, Lorelei A., Cancel-Tassin, Géraldine, Koutros, Stella, Sørensen, Karina Dalsgaard, Grindedal, Eli Marie, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry S., Lu, Yong-Jie, Giles, Graham G., MacInnis, Robert J., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanfrod, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Nielsen, Sune F., Brenner, Hermann, Maier, Christiane, Logothetis, Christopher J., John, Esther M., Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Castelao, Jose Esteban, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa, Pandha, Hardev, Thibodeau, Stephen N., Hunter, David J., Kraft, Peter, Blot, William J., Riboli, Elio, Yarmolinsky, James, Robinson, Jamie W., Mariosa, Daniela, Karhunen, Ville, Huang, Jian, Dimou, Niki, Murphy, Neil, Burrows, Kimberley, Bouras, Emmanouil, Smith-Byrne, Karl, Lewis, Sarah J., Galesloot, Tessel E., Vermeulen, Sita, Martin, Paul, Hou, Lifang, Newcomb, Polly A., White, Emily, Wu, Anna H., Le Marchand, Loïc, Phipps, Amanda I., Buchanan, Daniel D., Zhao, Sizheng Steven, Gill, Dipender, Chanock, Stephen J., Purdue, Mark P., Davey Smith, George, Herzig, Karl-Heinz, Järvelin, Marjo-Riitta, Amos, Chris I., Dehghan, Abbas, Gunter, Marc J., Tsilidis, Kostas K., and Martin, Richard M.

Published
2024
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14. The association between genetically elevated polyunsaturated fatty acids and risk of cancer

Author

Tintle, Nathan, Rice, Terri, Cheng, Iona, Jenkins, Mark, Gallinger, Steve, Cornish, Alex J., Sud, Amit, Vijayakrishnan, Jayaram, Wrensch, Margaret, Johansson, Mattias, Norman, Aaron D., Klein, Alison, Clay-Gilmour, Alyssa, Franke, Andre, Ardisson Korat, Andres V., Wheeler, Bill, Nilsson, Björn, Smith, Caren, Heng, Chew-Kiat, Song, Ci, Riadi, David, Claus, Elizabeth B., Ellinghaus, Eva, Ostroumova, Evgenia, Hosnijeh, de Vathaire, Florent, Cugliari, Giovanni, Matullo, Giuseppe, Oi-Lin Ng, Irene, Passow, Jeanette E., Foo, Jia Nee, Han, Jiali, Liu, Jianjun, Barnholtz-Sloan, Jill, Schildkraut, Joellen M., Maris, John, Wiemels, Joseph L., Hemminki, Kari, Yang, Keming, Kiemeney, Lambertus A., Wu, Lang, Amundadottir, Laufey, Stern, Marc-Henri, Boutron, Marie-Christine, Iles, Mark Martin, Purdue, Mark P., Stanulla, Martin, Bondy, Melissa, Gaudet, Mia, Mobuchon, Lenha, Camp, Nicola J., Sham, Pak Chung, Guénel, Pascal, Brennan, Paul, Taylor, Philip R., Ostrom, Quinn, Stolzenberg-Solomon, Rachael, Dorajoo, Rajkumar, Houlston, Richard, Jenkins, Robert B., Diskin, Sharon, Berndt, Sonja I., Tsavachidis, Spiridon, Channock, Stephen J., Harrison, Tabitha, Galesloot, Tessel, Gyllensten, Ulf, Joseph, Vijai, Shi, Y., Yang, Wenjian, Lin, Yi, Van Den Eeden, Stephen K., Haycock, Philip C., Borges, Maria Carolina, Burrows, Kimberley, Lemaitre, Rozenn N., Burgess, Stephen, Khankari, Nikhil K., Tsilidis, Konstantinos K., Gaunt, Tom R., Hemani, Gibran, Zheng, Jie, Truong, Therese, Birmann, Brenda M., OMara, Tracy, Spurdle, Amanda B., Iles, Mark M., Law, Matthew H., Slager, Susan L., Saberi Hosnijeh, Fatemeh, Mariosa, Daniela, Cotterchio, Michelle, Cerhan, James R., Peters, Ulrike, Enroth, Stefan, Gharahkhani, Puya, Le Marchand, Loic, Williams, Ann C., Block, Robert C., Amos, Christopher I., Hung, Rayjean J., Zheng, Wei, Gunter, Marc J., Smith, George Davey, Relton, Caroline, and Martin, Richard M.

Published
2023
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18. Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers

Author

Smith-Byrne, Karl, primary, Hedman, Åsa, additional, Dimitriou, Marios, additional, Desai, Trishna, additional, Sokolov, Alexandr V., additional, Schioth, Helgi B., additional, Koprulu, Mine, additional, Pietzner, Maik, additional, Langenberg, Claudia, additional, Atkins, Joshua, additional, Penha, Ricardo Cortez, additional, McKay, James, additional, Brennan, Paul, additional, Zhou, Sirui, additional, Richards, Brent J., additional, Yarmolinsky, James, additional, Martin, Richard M., additional, Borlido, Joana, additional, Mu, Xinmeng J., additional, Butterworth, Adam, additional, Shen, Xia, additional, Wilson, Jim, additional, Assimes, Themistocles L., additional, Hung, Rayjean J., additional, Amos, Christopher, additional, Purdue, Mark, additional, Rothman, Nathaniel, additional, Chanock, Stephen, additional, Travis, Ruth C., additional, Johansson, Mattias, additional, and Mälarstig, Anders, additional

Published
2024
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19. Identification of potential mediators of the relationship between body mass index and colorectal cancer: a Mendelian randomization analysis

Author

Bouras, Emmanouil, primary, Gill, Dipender, additional, Zuber, Verena, additional, Murphy, Neil, additional, Dimou, Niki, additional, Aleksandrova, Krasimira, additional, Lewis, Sarah J, additional, Martin, Richard M, additional, Yarmolinsky, James, additional, Albanes, Demetrius, additional, Brenner, Hermann, additional, Castellví-Bel, Sergi, additional, Chan, Andrew T, additional, Cheng, Iona, additional, Gruber, Stephen, additional, Van Guelpen, Bethany, additional, Li, Christopher I, additional, Le Marchand, Loic, additional, Newcomb, Polly A, additional, Ogino, Shuji, additional, Pellatt, Andrew, additional, Schmit, Stephanie L, additional, Wolk, Alicja, additional, Wu, Anna H, additional, Peters, Ulrike, additional, Gunter, Marc J, additional, and Tsilidis, Konstantinos K, additional

Published
2024
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20. Applying Mendelian randomization to appraise causality in relationships between nutrition and cancer

Author

Wade, Kaitlin H., Yarmolinsky, James, Giovannucci, Edward, Lewis, Sarah J., Millwood, Iona Y., Munafò, Marcus R., Meddens, Fleur, Burrows, Kimberley, Bell, Joshua A., Davies, Neil M., Mariosa, Daniela, Kanerva, Noora, Vincent, Emma E., Smith-Byrne, Karl, Guida, Florence, Gunter, Marc J., Sanderson, Eleanor, Dudbridge, Frank, Burgess, Stephen, Cornelis, Marilyn C., Richardson, Tom G., Borges, Maria Carolina, Bowden, Jack, Hemani, Gibran, Cho, Yoonsu, Spiller, Wes, Richmond, Rebecca C., Carter, Alice R., Langdon, Ryan, Lawlor, Deborah A., Walters, Robin G., Vimaleswaran, Karani Santhanakrishnan, Anderson, Annie, Sandu, Meda R., Tilling, Kate, Davey Smith, George, Martin, Richard M., and Relton, Caroline L.

Published
2022
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22. Circulating inflammatory cytokines and risk of five cancers: a Mendelian randomization analysis

Author

Bouras, Emmanouil, Karhunen, Ville, Gill, Dipender, Huang, Jian, Haycock, Philip C., Gunter, Marc J., Johansson, Mattias, Brennan, Paul, Key, Tim, Lewis, Sarah J., Martin, Richard M., Murphy, Neil, Platz, Elizabeth A., Travis, Ruth, Yarmolinsky, James, Zuber, Verena, Martin, Paul, Katsoulis, Michail, Freisling, Heinz, Nøst, Therese Haugdahl, Schulze, Matthias B., Dossus, Laure, Hung, Rayjean J., Amos, Christopher I., Ahola-Olli, Ari, Palaniswamy, Saranya, Männikkö, Minna, Auvinen, Juha, Herzig, Karl-Heinz, Keinänen-Kiukaanniemi, Sirkka, Lehtimäki, Terho, Salomaa, Veikko, Raitakari, Olli, Salmi, Marko, Jalkanen, Sirpa, Jarvelin, Marjo-Riitta, Dehghan, Abbas, and Tsilidis, Konstantinos K.

Published
2022
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24. Investigating the effect of sexual behaviour on oropharyngeal cancer risk: a methodological assessment of Mendelian randomization

Author

Gormley, Mark, Dudding, Tom, Kachuri, Linda, Burrows, Kimberley, Chong, Amanda H. W., Martin, Richard M., Thomas, Steven J., Tyrrell, Jessica, Ness, Andrew R., Brennan, Paul, Munafò, Marcus R., Pring, Miranda, Boccia, Stefania, Olshan, Andrew F., Diergaarde, Brenda, Hung, Rayjean J., Liu, Geoffrey, Tajara, Eloiza H., Severino, Patricia, Toporcov, Tatiana N., Lacko, Martin, Waterboer, Tim, Brenner, Nicole, Smith, George Davey, Vincent, Emma E., and Richmond, Rebecca C.

Published
2022
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25. Prostate cancer–Exercise and Metformin Trial (Pre-EMpT): study protocol for a feasibility factorial randomized controlled trial in men with localised or locally advanced prostate cancer

Author

McGeagh, Lucy, Robles, Luke A., Persad, Raj, Rowe, Edward, Bahl, Amit, Aning, Jonathan, Koupparis, Anthony, Abrams, Paul, Perks, Claire, Holly, Jeffrey, Johnson, Lyndsey, Shiridzinomwa, Constance, Challapalli, Amarnath, Shingler, Ellie, Taylor, Hilary, Oxley, Jon, Sandu, Meda, Martin, Richard M., and Lane, J. Athene

Published
2022
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29. Optimising the use of the prostate- specific antigen blood test in asymptomatic men for early prostate cancer detection in primary care: report from a UK clinical consensus.

Author

Harding, Thomas A, Martin, Richard M, Merriel, Samuel WD, Jones, Robert, O'Sullivan, Joe M, Kirby, Mike, Olajide, Oluwabunmi, Norman, Alexander, Bhatt, Jaimin, Hulson, Oliver, Martins, Tanimola, Gnanapragasam, Vincent J, Aning, Jonathan, Burgess, Meg, Rosario, Derek J, Pashayan, Nora, Tesfai, Abel, Norori, Natalia, Rylance, Amy, and Seggie, Andrew

Subjects
EARLY detection of cancer, PROSTATE cancer patients, PRIMARY health care, ASYMPTOMATIC patients, PROSTATE-specific antigen
Abstract

Background: Screening is not recommended for prostate cancer in the UK. Asymptomatic men aged ≥50 years can request a prostate-specific antigen (PSA) test following counselling on potential harms and benefits. There are areas of clinical uncertainty among GPs, resulting in the content and quality of counselling varying. Aim: To produce a consensus that can influence guidelines for UK primary care on the optimal use of the PSA test in asymptomatic men for early prostate cancer detection. Design and setting: Prostate Cancer UK facilitated a RAND/UCLA consensus. Method: Statements covering five topics were developed with a subgroup of experts. A panel of 15 experts in prostate cancer scored (round one) statements on a scale of one (strongly disagree) to nine (strongly agree). Panellists met to discuss statements before rescoring (round two). A lived experience panel of seven men scored a subset of statements with outcomes fed into the main panel. Results: Of the initial 94 statements reviewed by the expert panel, a final 48/85 (56%) achieved consensus. In the absence of screening, there was consensus on proactive approaches to initiate discussions about the PSA test with men who were at higher-than-average risk. Conclusion: Improvements in the prostate cancer diagnostic pathway may have reduced some of the harms associated with PSA testing; however, several areas of uncertainty remain in relation to screening, including optimal PSA thresholds for referral and intervals for retesting. There is consensus on proactive approaches to testing in higher-than-average risk groups. This should prompt a review of current guidelines. [ABSTRACT FROM AUTHOR]

Published
2024

31. A proteogenomic analysis of the adiposity colorectal cancer relationship identifies GREM1 as a probable mediator

Author

Lee, Matthew A, primary, Hatcher, Charlie A, additional, Hazelwood, Emma, additional, Goudswaard, Lucy J, additional, Tsilidis, Konstantinos K, additional, Vincent, Emma E, additional, Martin, Richard M, additional, Smith-Byrne, Karl, additional, Brenner, Hermann, additional, Cheng, Iona, additional, Kweon, Sun-Seog, additional, Le Marchand, Loic, additional, Newcomb, Polly A, additional, Schoen, Rovert E, additional, Peters, Ulrike, additional, Gunter, Marc J, additional, Van Guelpen, Bethany, additional, and Murphy, Neil, additional

Published
2024
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33. Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis

Author

Yarmolinsky, James, primary, Robinson, Jamie W., additional, Mariosa, Daniela, additional, Karhunen, Ville, additional, Huang, Jian, additional, Dimou, Niki, additional, Murphy, Neil, additional, Burrows, Kimberley, additional, Bouras, Emmanouil, additional, Smith-Byrne, Karl, additional, Lewis, Sarah J., additional, Galesloot, Tessel E., additional, Kiemeney, Lambertus A., additional, Vermeulen, Sita, additional, Martin, Paul, additional, Albanes, Demetrius, additional, Hou, Lifang, additional, Newcomb, Polly A., additional, White, Emily, additional, Wolk, Alicja, additional, Wu, Anna H., additional, Le Marchand, Loïc, additional, Phipps, Amanda I., additional, Buchanan, Daniel D., additional, Zhao, Sizheng Steven, additional, Gill, Dipender, additional, Chanock, Stephen J., additional, Purdue, Mark P., additional, Davey Smith, George, additional, Brennan, Paul, additional, Herzig, Karl-Heinz, additional, Järvelin, Marjo-Riitta, additional, Amos, Chris I., additional, Hung, Rayjean J., additional, Dehghan, Abbas, additional, Johansson, Mattias, additional, Gunter, Marc J., additional, Tsilidis, Kostas K., additional, Martin, Richard M., additional, Landi, Maria Teresa, additional, Stevens, Victoria, additional, Wang, Ying, additional, Albanes, Demetrios, additional, Caporaso, Neil, additional, Amos, Christopher I., additional, Shete, Sanjay, additional, Bickeböller, Heike, additional, Risch, Angela, additional, Houlston, Richard, additional, Lam, Stephen, additional, Tardon, Adonina, additional, Chen, Chu, additional, Bojesen, Stig E., additional, Wichmann, H-Erich, additional, Christiani, David, additional, Rennert, Gadi, additional, Arnold, Susanne, additional, Field, John K., additional, Le Marchand, Loic, additional, Melander, Olle, additional, Brunnström, Hans, additional, Liu, Geoffrey, additional, Andrew, Angeline, additional, Shen, Hongbing, additional, Zienolddiny, Shan, additional, Grankvist, Kjell, additional, Johansson, Mikael, additional, Teare, M. Dawn, additional, Hong, Yun-Chul, additional, Yuan, Jian-Min, additional, Lazarus, Philip, additional, Schabath, Matthew B., additional, Aldrich, Melinda C., additional, Eeles, Rosalind A., additional, Haiman, Christopher A., additional, Kote-Jarai, Zsofia, additional, Schumacher, Fredrick R., additional, Benlloch, Sara, additional, Al Olama, Ali Amin, additional, Muir, Kenneth R., additional, Berndt, Sonja I., additional, Conti, David V., additional, Wiklund, Fredrik, additional, Chanock, Stephen, additional, Tangen, Catherine M., additional, Batra, Jyotsna, additional, Clements, Judith A., additional, Grönberg, Henrik, additional, Pashayan, Nora, additional, Schleutker, Johanna, additional, Weinstein, Stephanie J., additional, West, Catharine M.L., additional, Mucci, Lorelei A., additional, Cancel-Tassin, Géraldine, additional, Koutros, Stella, additional, Sørensen, Karina Dalsgaard, additional, Grindedal, Eli Marie, additional, Neal, David E., additional, Hamdy, Freddie C., additional, Donovan, Jenny L., additional, Travis, Ruth C., additional, Hamilton, Robert J., additional, Ingles, Sue Ann, additional, Rosenstein, Barry S., additional, Lu, Yong-Jie, additional, Giles, Graham G., additional, MacInnis, Robert J., additional, Kibel, Adam S., additional, Vega, Ana, additional, Kogevinas, Manolis, additional, Penney, Kathryn L., additional, Park, Jong Y., additional, Stanfrod, Janet L., additional, Cybulski, Cezary, additional, Nordestgaard, Børge G., additional, Nielsen, Sune F., additional, Brenner, Hermann, additional, Maier, Christiane, additional, Logothetis, Christopher J., additional, John, Esther M., additional, Teixeira, Manuel R., additional, Neuhausen, Susan L., additional, De Ruyck, Kim, additional, Razack, Azad, additional, Newcomb, Lisa F., additional, Lessel, Davor, additional, Kaneva, Radka, additional, Usmani, Nawaid, additional, Claessens, Frank, additional, Townsend, Paul A., additional, Castelao, Jose Esteban, additional, Roobol, Monique J., additional, Menegaux, Florence, additional, Khaw, Kay-Tee, additional, Cannon-Albright, Lisa, additional, Pandha, Hardev, additional, Thibodeau, Stephen N., additional, Hunter, David J., additional, Kraft, Peter, additional, Blot, William J., additional, and Riboli, Elio, additional

Published
2024
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42. Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial.

Author

Martin, Richard M., Turner, Emma L., Young, Grace J., Metcalfe, Chris, Walsh, Eleanor I., Lane, J. Athene, Sterne, Jonathan A. C., Noble, Sian, Holding, Peter, Ben-Shlomo, Yoav, Williams, Naomi J., Pashayan, Nora, Bui, Mai Ngoc, Albertsen, Peter C., Seibert, Tyler M., Zietman, Anthony L., Oxley, Jon, Adolfsson, Jan, Mason, Malcolm D., and Davey Smith, George

Abstract

This secondary analysis of a randomized clinical trial assesses whether screening for prostate-specific antigen reduces prostate cancer mortality at 15-year follow-up. Key Points: Question: In men aged 50 to 69 years, does a single invitation for a prostate-specific antigen (PSA) screening test reduce prostate cancer mortality at 15-year follow-up compared with no invitation for testing? Findings: In this secondary analysis of a randomized clinical trial of 415 357 men aged 50 to 69 years randomized to a single invitation for PSA screening (n = 195 912) or a control group without PSA screening (n = 219 445) and followed up for a median of 15 years, risk of death from prostate cancer was lower in the group invited to screening (0.69% vs 0.78%; mean difference, 0.09%) compared with the control group. Meaning: Compared with no invitation for routine PSA testing, a single invitation for a PSA screening test reduced prostate cancer mortality at a median follow-up of 15 years, but the absolute mortality benefit was small. Importance: The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear. Objective: To evaluate the effect of a single invitation for PSA screening on prostate cancer–specific mortality at a median 15-year follow-up compared with no invitation for screening. Design, Setting, and Participants: This secondary analysis of the CAP randomized clinical trial included men aged 50 to 69 years identified at 573 primary care practices in England and Wales. Primary care practices were randomized between September 25, 2001, and August 24, 2007, and men were enrolled between January 8, 2002, and January 20, 2009. Follow-up was completed on March 31, 2021. Intervention: Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher. The control group received standard practice (no invitation). Main Outcomes and Measures: The primary outcome was reported previously. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The 4 remaining prespecified secondary outcomes at 15-year follow-up were prostate cancer–specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis. Results: Of 415 357 eligible men (mean [SD] age, 59.0 [5.6] years), 98% were included in these analyses. Overall, 12 013 and 12 958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08% [95% CI, 6.95%-7.21%] and 6.94% [95% CI, 6.82%-7.06%], respectively). At a median 15-year follow-up, 1199 men in the intervention group (0.69% [95% CI, 0.65%-0.73%]) and 1451 men in the control group (0.78% [95% CI, 0.73%-0.82%]) died of prostate cancer (rate ratio [RR], 0.92 [95% CI, 0.85-0.99]; P =.03). Compared with the control, the PSA screening intervention increased detection of low-grade (Gleason score [GS] ≤6: 2.2% vs 1.6%; P <.001) and localized (T1/T2: 3.6% vs 3.1%; P <.001) disease but not intermediate (GS of 7), high-grade (GS ≥8), locally advanced (T3), or distally advanced (T4/N1/M1) tumors. There were 45 084 all-cause deaths in the intervention group (23.2% [95% CI, 23.0%-23.4%]) and 50 336 deaths in the control group (23.3% [95% CI, 23.1%-23.5%]) (RR, 0.97 [95% CI, 0.94-1.01]; P =.11). Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, the absolute reduction in deaths was small. Trial Registration: isrctn.org Identifier: ISRCTN92187251 [ABSTRACT FROM AUTHOR]

Published
2024
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46. Leisure time television watching, computer use and risks of breast, colorectal and prostate cancer: A Mendelian randomisation analysis.

Author

Papadimitriou, Nikos, Kazmi, Nabila, Dimou, Niki, Tsilidis, Konstantinos K., Martin, Richard M., Lewis, Sarah J., Lynch, Brigid M., Hoffmeister, Michael, Sun-Seog Kweon, Li Li, Milne, Roger L., Sakoda, Lori C., Schoen, Robert E., Phipps, Amanda I., Figueiredo, Jane C., Peters, Ulrike, Dixon-Suen, Suzanne C., Gunter, Marc J., and Murphy, Neil

Subjects
COLORECTAL cancer, PROSTATE cancer, TELEVISION viewing, LEISURE, GENOME-wide association studies
Abstract

Background: Sedentary behaviours have been associated with increased risks of some common cancers in epidemiological studies; however, it is unclear if these associations are causal. Methods: We used univariable and multivariable two-sample Mendelian randomisation (MR) to examine potential causal relationships between sedentary behaviours and risks of breast, colorectal and prostate cancer. Genetic variants associated with self-reported leisure television watching and computer use were identified from a recent genome-wide association study (GWAS). Data related to cancer risk were obtained from cancer GWAS consortia. A series of sensitivity analyses were applied to examine the robustness of the results to the presence of confounding. Results: A 1-standard deviation (SD: 1.5h/day) increment in hours of television watching increased risk of breast cancer (OR per 1-SD: 1.15, 95% confidence interval [CI]: 1.05–1.26) and colorectal cancer (OR per 1-SD: 1.32, 95% CI: 1.16– 1.49) while there was little evidence of an association for prostate cancer risk (OR per 1-SD: 0.94, 95% CI: 0.84–1.06). After adjusting for years of education, the effect estimates for television watching were attenuated (breast cancer, OR per 1-SD: 1.08, 95% CI: 0.92–1.27; colorectal cancer, OR per 1-SD: 1.08, 95% CI: 0.90–1.31). Post hoc analyses showed that years of education might have a possible confounding and mediating role in the association between television watching with breast and colorectal cancer. Consistent results were observed for each cancer site according to sex (colorectal cancer), anatomical subsites and cancer subtypes. There was little evidence of associations between genetically predicted computer use and cancer risk. Conclusions: Our univariable analysis identified some positive associations between hours of television watching and risks of breast and colorectal cancer. However, further adjustment for additional lifestyle factors especially years of education attenuated these results. Future studies using objective measures of exposure can provide new insights into the possible role of sedentary behaviour in cancer development. [ABSTRACT FROM AUTHOR]

Published
2024
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47. Kidney Function and Risk of Renal Cell Carcinoma

Author

Alcala, Karine, primary, Zahed, Hana, additional, Cortez Cardoso Penha, Ricardo, additional, Alcala, Nicolas, additional, Robbins, Hilary A., additional, Smith-Byrne, Karl, additional, Martin, Richard M., additional, Muller, David C., additional, Brennan, Paul, additional, and Johansson, Mattias, additional

Published
2023
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49. Genetically proxied therapeutic inhibition of antihypertensive drug targets and risk of common cancers: A mendelian randomization analysis

Author

Yarmolinsky, James, Díez-Obrero, Virginia, Richardson, Tom G., Pigeyre, Marie, Sjaarda, Jennifer, Paré, Guillaume, Walker, Venexia M., Vincent, Emma E., Tan, Vanessa Y., Obón-Santacana, Mireia, Albanes, Demetrius, Hampe, Jochen, Gsur, Andrea, Hampel, Heather, Pai, Rish K., Jenkins, Mark, Gallinger, Steven, Casey, Graham, Zheng, Wei, Amos, Christopher I., Smith, George Davey, Martin, Richard M., and Moreno, Victor

Subjects
Colorectal cancer -- Risk factors, ACE inhibitors -- Complications and side effects, Drug targeting -- Models -- Genetic aspects, Hypertension -- Drug therapy -- Models, Biological sciences
Abstract

Background Epidemiological studies have reported conflicting findings on the potential adverse effects of long-term antihypertensive medication use on cancer risk. Naturally occurring variation in genes encoding antihypertensive drug targets can be used as proxies for these targets to examine the effect of their long-term therapeutic inhibition on disease outcomes. Methods and findings We performed a mendelian randomization analysis to examine the association between genetically proxied inhibition of 3 antihypertensive drug targets and risk of 4 common cancers (breast, colorectal, lung, and prostate). Single-nucleotide polymorphisms (SNPs) in ACE, ADRB1, and SLC12A3 associated (P < 5.0 x 10.sup.-8) with systolic blood pressure (SBP) in genome-wide association studies (GWAS) were used to proxy inhibition of angiotensin-converting enzyme (ACE), [beta]-1 adrenergic receptor (ADRB1), and sodium-chloride symporter (NCC), respectively. Summary genetic association estimates for these SNPs were obtained from GWAS consortia for the following cancers: breast (122,977 cases, 105,974 controls), colorectal (58,221 cases, 67,694 controls), lung (29,266 cases, 56,450 controls), and prostate (79,148 cases, 61,106 controls). Replication analyses were performed in the FinnGen consortium (1,573 colorectal cancer cases, 120,006 controls). Cancer GWAS and FinnGen consortia data were restricted to individuals of European ancestry. Inverse-variance weighted random-effects models were used to examine associations between genetically proxied inhibition of these drug targets and risk of cancer. Multivariable mendelian randomization and colocalization analyses were employed to examine robustness of findings to violations of mendelian randomization assumptions. Genetically proxied ACE inhibition equivalent to a 1-mm Hg reduction in SBP was associated with increased odds of colorectal cancer (odds ratio (OR) 1.13, 95% CI 1.06 to 1.22; P = 3.6 x 10.sup.-4). This finding was replicated in the FinnGen consortium (OR 1.40, 95% CI 1.02 to 1.92; P = 0.035). There was little evidence of association of genetically proxied ACE inhibition with risk of breast cancer (OR 0.98, 95% CI 0.94 to 1.02, P = 0.35), lung cancer (OR 1.01, 95% CI 0.92 to 1.10; P = 0.93), or prostate cancer (OR 1.06, 95% CI 0.99 to 1.13; P = 0.08). Genetically proxied inhibition of ADRB1 and NCC were not associated with risk of these cancers. The primary limitations of this analysis include the modest statistical power for analyses of drug targets in relation to some less common histological subtypes of cancers examined and the restriction of the majority of analyses to participants of European ancestry. Conclusions In this study, we observed that genetically proxied long-term ACE inhibition was associated with an increased risk of colorectal cancer, warranting comprehensive evaluation of the safety profiles of ACE inhibitors in clinical trials with adequate follow-up. There was little evidence to support associations across other drug target-cancer risk analyses, consistent with findings from short-term randomized controlled trials for these medications., Author(s): James Yarmolinsky 1,2,*, Virginia Díez-Obrero 3,4,5, Tom G. Richardson 1,2, Marie Pigeyre 6,7,8, Jennifer Sjaarda 6,7,9, Guillaume Paré 6,7,9,10, Venexia M. Walker 1,2,11, Emma E. Vincent 1,2,12, Vanessa Y. [...]

Published
2022
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50. Genetic predisposition to metabolically unfavourable adiposity and prostate cancer risk: A Mendelian randomization analysis

Author

Perez‐Cornago, Aurora, primary, Smith‐Byrne, Karl, additional, Hazelwood, Emma, additional, Watling, Cody Z., additional, Martin, Susan, additional, Frayling, Timothy, additional, Lewis, Sarah, additional, Martin, Richard M., additional, Yaghootkar, Hanieh, additional, Travis, Ruth C., additional, and Key, Timothy J., additional

Published
2023
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