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3. Multiparameter prediction of myeloid neoplasia risk

Author

Gu, Muxin, Kovilakam, Sruthi Cheloor, Dunn, William G., Marando, Ludovica, Barcena, Clea, Mohorianu, Irina, Smith, Alexandra, Kar, Siddhartha P., Fabre, Margarete A., Gerstung, Moritz, Cargo, Catherine A., Malcovati, Luca, Quiros, Pedro M., and Vassiliou, George S.

Published
2023
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5. Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions

Author

Dareng, Eileen O., Coetzee, Simon G., Tyrer, Jonathan P., Peng, Pei-Chen, Rosenow, Will, Chen, Stephanie, Davis, Brian D., Dezem, Felipe Segato, Seo, Ji-Heui, Nameki, Robbin, Reyes, Alberto L., Aben, Katja K.H., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Bandera, Elisa V., Beane Freeman, Laura E., Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia V., Bolton, Kelly L., Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Cai, Hui, Campbell, Ian, Cannioto, Rikki, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chenevix-Trench, Georgia, Chiew, Yoke-Eng, Cook, Linda S., DeFazio, Anna, Dennis, Joe, Doherty, Jennifer A., Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana M., Ene, Gabrielle, Fasching, Peter A., Flanagan, James M., Fortner, Renée T., Fostira, Florentia, Gentry-Maharaj, Aleksandra, Giles, Graham G., Goodman, Marc T., Gronwald, Jacek, Haiman, Christopher A., Håkansson, Niclas, Heitz, Florian, Hildebrandt, Michelle A.T., Høgdall, Estrid, Høgdall, Claus K., Huang, Ruea-Yea, Jensen, Allan, Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony N., Kelemen, Linda E., Kennedy, Catherine J., Khusnutdinova, Elza K., Kiemeney, Lambertus A., Kjaer, Susanne K., Kupryjanczyk, Jolanta, Labrie, Marilyne, Lambrechts, Diether, Larson, Melissa C., Le, Nhu D., Lester, Jenny, Li, Lian, Lubiński, Jan, Lush, Michael, Marks, Jeffrey R., Matsuo, Keitaro, May, Taymaa, McLaughlin, John R., McNeish, Iain A., Menon, Usha, Missmer, Stacey, Modugno, Francesmary, Moffitt, Melissa, Monteiro, Alvaro N., Moysich, Kirsten B., Narod, Steven A., Nguyen-Dumont, Tu, Odunsi, Kunle, Olsson, Håkan, Onland-Moret, N. Charlotte, Park, Sue K., Pejovic, Tanja, Permuth, Jennifer B., Piskorz, Anna, Prokofyeva, Darya, Riggan, Marjorie J., Risch, Harvey A., Rodríguez-Antona, Cristina, Rossing, Mary Anne, Sandler, Dale P., Setiawan, V. Wendy, Shan, Kang, Song, Honglin, Southey, Melissa C., Steed, Helen, Sutphen, Rebecca, Swerdlow, Anthony J., Teo, Soo Hwang, Terry, Kathryn L., Thompson, Pamela J., Vestrheim Thomsen, Liv Cecilie, Titus, Linda, Trabert, Britton, Travis, Ruth, Tworoger, Shelley S., Valen, Ellen, Van Nieuwenhuysen, Els, Edwards, Digna Velez, Vierkant, Robert A., Webb, Penelope M., Weinberg, Clarice R., Weise, Rayna Matsuno, Wentzensen, Nicolas, White, Emily, Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zeinomar, Nur, Zheng, Wei, Ziogas, Argyrios, Berchuck, Andrew, Goode, Ellen L., Huntsman, David G., Pearce, Celeste L., Ramus, Susan J., Sellers, Thomas A., Freedman, Matthew L., Lawrenson, Kate, Schildkraut, Joellen M., Hazelett, Dennis, Plummer, Jasmine T., Kar, Siddhartha, Jones, Michelle R., Pharoah, Paul D.P., and Gayther, Simon A.

Published
2024
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7. Prevalence and significance of DDX41 gene variants in the general population

Author

Ambrose, J. C., Arumugam, P., Bevers, R., Bleda, M., Boardman-Pretty, F., Boustred, C. R., Brittain, H., Brown, M. A., Caulfield, M. J., Chan, G. C., Giess, A., Griffin, J. N., Hamblin, A., Henderson, S., Hubbard, T. J. P., Jackson, R., Jones, L. J., Kasperaviciute, D., Kayikci, M., Kousathanas, A., Lahnstein, L., Lakey, A., Leigh, S. E. A., Leong, I. U. S., Lopez, F. J., Maleady-Crowe, F., McEntagart, M., Minneci, F., Mitchell, J., Moutsianas, L., Mueller, M., Murugaesu, N., Need, A. C., O‘Donovan, P., Odhams, C. A., Patch, C., Perez-Gil, D., Pereira, M. B., Pullinger, J., Rahim, T., Rendon, A., Rogers, T., Savage, K., Sawant, K., Scott, R. H., Siddiq, A., Sieghart, A., Smith, S. C., Sosinsky, A., Stuckey, A., Tanguy, M., Taylor Tavares, A. L., Thomas, E. R. A., Thompson, S. R., Tucci, A., Welland, M. J., Williams, E., Witkowska, K., Wood, S. M., Zarowiecki, M., Cheloor Kovilakam, Sruthi, Gu, Muxin, Dunn, William G., Marando, Ludovica, Barcena, Clea, Nik-Zainal, Serena, Mohorianu, Irina, Kar, Siddhartha P., Fabre, Margarete A., Quiros, Pedro M., and Vassiliou, George S.

Published
2023
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20. The association between weight at birth and breast cancer risk revisited using Mendelian randomisation

Author

Kar, Siddhartha P., Andrulis, Irene L., Brenner, Hermann, Burgess, Stephen, Chang-Claude, Jenny, Considine, Daniel, Dörk, Thilo, Evans, Dafydd Gareth R., Gago-Domínguez, Manuela, Giles, Graham G., Hartman, Mikael, Huo, Dezheng, Kaaks, Rudolf, Li, Jingmei, Lophatananon, Artitaya, Margolin, Sara, Milne, Roger L., Muir, Kenneth R., Olsson, Håkan, Punie, Kevin, Radice, Paolo, Simard, Jacques, Tamimi, Rulla M., Van Nieuwenhuysen, Els, Wendt, Camilla, Zheng, Wei, and Pharoah, Paul D. P.

Published
2019

22. Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women

Author

Lawrenson, Kate, Song, Fengju, Hazelett, Dennis J., Kar, Siddhartha P., Tyrer, Jonathan, Phelan, Catherine M., Corona, Rosario I., Rodríguez-Malavé, Norma I., Seo, Ji-Hei, Adler, Emily, Coetzee, Simon G., Segato, Felipe, Fonseca, Marcos A.S., Amos, Christopher I., Carney, Michael E., Chenevix-Trench, Georgia, Choi, Jiyeob, Doherty, Jennifer A., Jia, Weihua, Jin, Gang J., Kim, Byoung-Gie, Le, Nhu D., Lee, Juyeon, Li, Lian, Lim, Boon K., Adenan, Noor A., Mizuno, Mika, Park, Boyoung, Pearce, Celeste L., Shan, Kang, Shi, Yongyong, Shu, Xiao-Ou, Sieh, Weiva, Thompson, Pamela J., Wilkens, Lynne R., Wei, Qingyi, Woo, Yin L., Yan, Li, Karlan, Beth Y., Freedman, Matthew L., Noushmehr, Houtan, Goode, Ellen L., Berchuck, Andrew, Sellers, Thomas A., Teo, Soo-Hwang, Zheng, Wei, Matsuo, Keitaro, Park, Sue, Chen, Kexin, Pharoah, Paul D.P., Gayther, Simon A., and Goodman, Marc T.

Published
2019
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30. Body size and composition and risk of site-specific cancers in the UK Biobank and large international consortia: A mendelian randomisation study

Author

Vithayathil, Mathew, Carter, Paul, Kar, Siddhartha, Mason, Amy M., Burgess, Stephen, and Larsson, Susanna C.

Subjects
Body size -- Health aspects, Body composition -- Health aspects, Cancer -- Risk factors -- Physiological aspects -- Genetic aspects, Body mass index -- Analysis, Biological sciences
Abstract

Background Evidence for the impact of body size and composition on cancer risk is limited. This mendelian randomisation (MR) study investigates evidence supporting causal relationships of body mass index (BMI), fat mass index (FMI), fat-free mass index (FFMI), and height with cancer risk. Methods and findings Single nucleotide polymorphisms (SNPs) were used as instrumental variables for BMI (312 SNPs), FMI (577 SNPs), FFMI (577 SNPs), and height (293 SNPs). Associations of the genetic variants with 22 site-specific cancers and overall cancer were estimated in 367,561 individuals from the UK Biobank (UKBB) and with lung, breast, ovarian, uterine, and prostate cancer in large international consortia. In the UKBB, genetically predicted BMI was positively associated with overall cancer (odds ratio [OR] per 1 kg/m.sup.2 increase 1.01, 95% confidence interval [CI] 1.00-1.02; p = 0.043); several digestive system cancers: stomach (OR 1.13, 95% CI 1.06-1.21; p < 0.001), esophagus (OR 1.10, 95% CI 1.03, 1.17; p = 0.003), liver (OR 1.13, 95% CI 1.03-1.25; p = 0.012), and pancreas (OR 1.06, 95% CI 1.01-1.12; p = 0.016); and lung cancer (OR 1.08, 95% CI 1.04-1.12; p < 0.001). For sex-specific cancers, genetically predicted elevated BMI was associated with an increased risk of uterine cancer (OR 1.10, 95% CI 1.05-1.15; p < 0.001) and with a lower risk of prostate cancer (OR 0.97, 95% CI 0.94-0.99; p = 0.009). When dividing cancers into digestive system versus non-digestive system, genetically predicted BMI was positively associated with digestive system cancers (OR 1.04, 95% CI 1.02-1.06; p < 0.001) but not with non-digestive system cancers (OR 1.01, 95% CI 0.99-1.02; p = 0.369). Genetically predicted FMI was positively associated with liver, pancreatic, and lung cancer and inversely associated with melanoma and prostate cancer. Genetically predicted FFMI was positively associated with non-Hodgkin lymphoma and melanoma. Genetically predicted height was associated with increased risk of overall cancer (OR per 1 standard deviation increase 1.09; 95% CI 1.05-1.12; p < 0.001) and multiple site-specific cancers. Similar results were observed in analyses using the weighted median and MR-Egger methods. Results based on consortium data confirmed the positive associations between BMI and lung and uterine cancer risk as well as the inverse association between BMI and prostate cancer, and, additionally, showed an inverse association between genetically predicted BMI and breast cancer. The main limitations are the assumption that genetic associations with cancer outcomes are mediated via the proposed risk factors and that estimates for some lower frequency cancer types are subject to low precision. Conclusions Our results show that the evidence for BMI as a causal risk factor for cancer is mixed. We find that BMI has a consistent causal role in increasing risk of digestive system cancers and a role for sex-specific cancers with inconsistent directions of effect. In contrast, increased height appears to have a consistent risk-increasing effect on overall and site-specific cancers., Author(s): Mathew Vithayathil 1, Paul Carter 2, Siddhartha Kar 2,3, Amy M. Mason 2, Stephen Burgess 2,4,*, Susanna C. Larsson 5,6 Background Obesity is a global epidemic [1] that is [...]

Published
2021
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31. Predicted Proteome Association Studies of Breast, Prostate, Ovarian, and Endometrial Cancers Implicate Plasma Protein Regulation in Cancer Susceptibility.

Author

Gregga, Isabelle, Pharoah, Paul D. P., Gayther, Simon A., Manichaikul, Ani, Hae Kyung Im, Kar, Siddhartha P., Schildkraut, Joellen M., and Wheeler, Heather E.

Abstract

Background: Predicting protein levels from genotypes for proteome-wide association studies (PWAS) may provide insight into the mechanisms underlying cancer susceptibility. Methods: We performed PWAS of breast, endometrial, ovarian, and prostate cancers and their subtypes in several large European-ancestry discovery consortia (effective sample size: 237,483 cases/317,006 controls) and tested the results for replication in an independent European-ancestry GWAS (31,969 cases/410,350 controls). We performed PWAS using the cancer GWAS summary statistics and two sets of plasma protein prediction models, followed by colocalization analysis. Results: Using Atherosclerosis Risk in Communities (ARIC) models, we identified 93 protein-cancer associations [false discovery rate (FDR) < 0.05]. We then performed a meta-analysis of the discovery and replication PWAS, resulting in 61 significant protein-cancer associations (FDR < 0.05). Ten of 15 protein-cancer pairs that could be tested using Trans-Omics for Precision Medicine (TOPMed) protein prediction models replicated with the same directions of effect in both cancer GWAS (P < 0.05). To further support our results, we applied Bayesian colocalization analysis and found colocalized SNPs for SERPINA3 protein levels and prostate cancer (posterior probability, PP = 0.65) and SNUPN protein levels and breast cancer (PP = 0.62). Conclusions: We used PWAS to identify potential biomarkers of hormone-related cancer risk. SNPs in SERPINA3 and SNUPN did not reach genome-wide significance for cancer in the original GWAS, highlighting the power of PWAS for novel locus discovery, with the added advantage of providing directions of protein effect. Impact: PWAS and colocalization are promising methods to identify potential molecular mechanisms underlying complex traits. [ABSTRACT FROM AUTHOR]

Published
2023
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33. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

Author

Phelan, Catherine M, Kuchenbaecker, Karoline B, Tyrer, Jonathan P, Kar, Siddhartha P, Lawrenson, Kate, Winham, Stacey J, Dennis, Joe, Pirie, Ailith, Riggan, Marjorie J, Chornokur, Ganna, Earp, Madalene A, Lyra, Jr, Paulo C, Lee, Janet M, Coetzee, Simon, Beesley, Jonathan, McGuffog, Lesley, Soucy, Penny, Dicks, Ed, Lee, Andrew, Barrowdale, Daniel, Lecarpentier, Julie, Leslie, Goska, Aalfs, Cora M, Aben, Katja K H, Adams, Marcia, Adlard, Julian, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia, Aravantinos, Gerasimos, Arnold, Norbert, Arun, Banu K, Arver, Brita, Azzollini, Jacopo, Balmaña, Judith, Banerjee, Susana N, Barjhoux, Laure, Barkardottir, Rosa B, Bean, Yukie, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q, Birrer, Michael J, Bjorge, Line, Black, Amanda, Blankstein, Kenneth, Blok, Marinus J, Bodelon, Clara, Bogdanova, Natalia, Bojesen, Anders, Bonanni, Bernardo, Borg, Åke, Bradbury, Angela R, Brenton, James D, Brewer, Carole, Brinton, Louise, Broberg, Per, Brooks-Wilson, Angela, Bruinsma, Fiona, Brunet, Joan, Buecher, Bruno, Butzow, Ralf, Buys, Saundra S, Caldes, Trinidad, Caligo, Maria A, Campbell, Ian, Cannioto, Rikki, Carney, Michael E, Cescon, Terence, Chan, Salina B, Chang-Claude, Jenny, Chanock, Stephen, Chen, Xiao Qing, Chiew, Yoke-Eng, Chiquette, Jocelyne, Chung, Wendy K, Claes, Kathleen B M, Conner, Thomas, Cook, Linda S, Cook, Jackie, Cramer, Daniel W, Cunningham, Julie M, D'Aloisio, Aimee A, Daly, Mary B, Damiola, Francesca, Damirovna, Sakaeva Dina, Dansonka-Mieszkowska, Agnieszka, Dao, Fanny, Davidson, Rosemarie, DeFazio, Anna, Delnatte, Capucine, Doheny, Kimberly F, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer Anne, Domchek, Susan M, Dorfling, Cecilia M, Dörk, Thilo, Dossus, Laure, Duran, Mercedes, Dürst, Matthias, Dworniczak, Bernd, Eccles, Diana, Edwards, Todd, Eeles, Ros, Eilber, Ursula, Ejlertsen, Bent, Ekici, Arif B, Ellis, Steve, Elvira, Mingajeva, Eng, Kevin H, Engel, Christoph, Evans, D Gareth, Fasching, Peter A, Ferguson, Sarah, Ferrer, Sandra Fert, Flanagan, James M, Fogarty, Zachary C, Fortner, Renée T, Fostira, Florentia, Foulkes, William D, Fountzilas, George, Fridley, Brooke L, Friebel, Tara M, Friedman, Eitan, Frost, Debra, Ganz, Patricia A, Garber, Judy, García, María J, Garcia-Barberan, Vanesa, Gehrig, Andrea, Gentry-Maharaj, Aleksandra, Gerdes, Anne-Marie, Giles, Graham G, Glasspool, Rosalind, Glendon, Gord, Godwin, Andrew K, Goldgar, David E, Goranova, Teodora, Gore, Martin, Greene, Mark H, Gronwald, Jacek, Gruber, Stephen, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hamann, Ute, Hansen, Thomas V O, Harrington, Patricia A, Harris, Holly R, Hauke, Jan, Hein, Alexander, Henderson, Alex, Hildebrandt, Michelle A T, Hillemanns, Peter, Hodgson, Shirley, Høgdall, Claus K, Høgdall, Estrid, Hogervorst, Frans B L, Holland, Helene, Hooning, Maartje J, Hosking, Karen, Huang, Ruea-Yea, Hulick, Peter J, Hung, Jillian, Hunter, David J, Huntsman, David G, Huzarski, Tomasz, Imyanitov, Evgeny N, Isaacs, Claudine, Iversen, Edwin S, Izatt, Louise, Izquierdo, Angel, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Jernetz, Mats, Jensen, Allan, Jensen, Uffe Birk, John, Esther M, Johnatty, Sharon, Jones, Michael E, Kannisto, Päivi, Karlan, Beth Y, Karnezis, Anthony, Kast, Karin, Kennedy, Catherine J, Khusnutdinova, Elza, Kiemeney, Lambertus A, Kiiski, Johanna I, Kim, Sung-Won, Kjaer, Susanne K, Köbel, Martin, Kopperud, Reidun K, Kruse, Torben A, Kupryjanczyk, Jolanta, Kwong, Ava, Laitman, Yael, Lambrechts, Diether, Larrañaga, Nerea, Larson, Melissa C, Lazaro, Conxi, Le, Nhu D, Le Marchand, Loic, Lee, Jong Won, Lele, Shashikant B, Leminen, Arto, Leroux, Dominique, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A, Liang, Dong, Liebrich, Clemens, Lilyquist, Jenna, Lipworth, Loren, Lissowska, Jolanta, Lu, Karen H, Lubinński, Jan, Luccarini, Craig, Lundvall, Lene, Mai, Phuong L, Mendoza-Fandiño, Gustavo, Manoukian, Siranoush, Massuger, Leon F A G, May, Taymaa, Mazoyer, Sylvie, McAlpine, Jessica N, McGuire, Valerie, McLaughlin, John R, McNeish, Iain, Meijers-Heijboer, Hanne, Meindl, Alfons, Menon, Usha, Mensenkamp, Arjen R, Merritt, Melissa A, Milne, Roger L, Mitchell, Gillian, Modugno, Francesmary, Moes-Sosnowska, Joanna, Moffitt, Melissa, Montagna, Marco, Moysich, Kirsten B, Mulligan, Anna Marie, Musinsky, Jacob, Nathanson, Katherine L, Nedergaard, Lotte, Ness, Roberta B, Neuhausen, Susan L, Nevanlinna, Heli, Niederacher, Dieter, Nussbaum, Robert L, Odunsi, Kunle, Olah, Edith, Olopade, Olufunmilayo I, Olsson, Håkan, Olswold, Curtis, O'Malley, David M, Ong, Kai-ren, Onland-Moret, N Charlotte, Orr, Nicholas, Orsulic, Sandra, Osorio, Ana, Palli, Domenico, Papi, Laura, Park-Simon, Tjoung-Won, Paul, James, Pearce, Celeste L, Pedersen, Inge Søkilde, Peeters, Petra H M, Peissel, Bernard, Peixoto, Ana, Pejovic, Tanja, Pelttari, Liisa M, Permuth, Jennifer B, Peterlongo, Paolo, Pezzani, Lidia, Pfeiler, Georg, Phillips, Kelly-Anne, Piedmonte, Marion, Pike, Malcolm C, Piskorz, Anna M, Poblete, Samantha R, Pocza, Timea, Poole, Elizabeth M, Poppe, Bruce, Porteous, Mary E, Prieur, Fabienne, Prokofyeva, Darya, Pugh, Elizabeth, Pujana, Miquel Angel, Pujol, Pascal, Radice, Paolo, Rantala, Johanna, Rappaport-Fuerhauser, Christine, Rennert, Gad, Rhiem, Kerstin, Rice, Patricia, Richardson, Andrea, Robson, Mark, Rodriguez, Gustavo C, Rodríguez-Antona, Cristina, Romm, Jane, Rookus, Matti A, Rossing, Mary Anne, Rothstein, Joseph H, Rudolph, Anja, Runnebaum, Ingo B, Salvesen, Helga B, Sandler, Dale P, Schoemaker, Minouk J, Senter, Leigha, Setiawan, V Wendy, Severi, Gianluca, Sharma, Priyanka, Shelford, Tameka, Siddiqui, Nadeem, Side, Lucy E, Sieh, Weiva, Singer, Christian F, Sobol, Hagay, Song, Honglin, Southey, Melissa C, Spurdle, Amanda B, Stadler, Zsofia, Steinemann, Doris, Stoppa-Lyonnet, Dominique, Sucheston-Campbell, Lara E, Sukiennicki, Grzegorz, Sutphen, Rebecca, Sutter, Christian, Swerdlow, Anthony J, Szabo, Csilla I, Szafron, Lukasz, Tan, Yen Y, Taylor, Jack A, Tea, Muy-Kheng, Teixeira, Manuel R, Teo, Soo-Hwang, Terry, Kathryn L, Thompson, Pamela J, Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L, Tihomirova, Laima, Tinker, Anna V, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Tone, Alicia, Trabert, Britton, Travis, Ruth C, Trichopoulou, Antonia, Tung, Nadine, Tworoger, Shelley S, van Altena, Anne M, Van Den Berg, David, van der Hout, Annemarie H, van der Luijt, Rob B, Van Heetvelde, Mattias, Van Nieuwenhuysen, Els, van Rensburg, Elizabeth J, Vanderstichele, Adriaan, Varon-Mateeva, Raymonda, Vega, Ana, Edwards, Digna Velez, Vergote, Ignace, Vierkant, Robert A, Vijai, Joseph, Vratimos, Athanassios, Walker, Lisa, Walsh, Christine, Wand, Dorothea, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Webb, Penelope M, Weinberg, Clarice R, Weitzel, Jeffrey N, Wentzensen, Nicolas, Whittemore, Alice S, Wijnen, Juul T, Wilkens, Lynne R, Wolk, Alicja, Woo, Michelle, Wu, Xifeng, Wu, Anna H, Yang, Hannah, Yannoukakos, Drakoulis, Ziogas, Argyrios, Zorn, Kristin K, Narod, Steven A, Easton, Douglas F, Amos, Christopher I, Schildkraut, Joellen M, Ramus, Susan J, Ottini, Laura, Goodman, Marc T, Park, Sue K, Kelemen, Linda E, Risch, Harvey A, Thomassen, Mads, Offit, Kenneth, Simard, Jacques, Schmutzler, Rita Katharina, Hazelett, Dennis, Monteiro, Alvaro N, Couch, Fergus J, Berchuck, Andrew, Chenevix-Trench, Georgia, Goode, Ellen L, Sellers, Thomas A, Gayther, Simon A, Antoniou, Antonis C, and Pharoah, Paul D P

Published
2017
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36. Association analysis identifies 65 new breast cancer risk loci

Author

Michailidou, Kyriaki, Lindström, Sara, Dennis, Joe, Beesley, Jonathan, Hui, Shirley, Kar, Siddhartha, Lemaçon, Audrey, Soucy, Penny, Glubb, Dylan, Rostamianfar, Asha, Bolla, Manjeet K., Wang, Qin, Tyrer, Jonathan, Dicks, Ed, Lee, Andrew, Wang, Zhaoming, Allen, Jamie, Keeman, Renske, Eilber, Ursula, French, Juliet D., Qing Chen, Xiao, Fachal, Laura, McCue, Karen, McCart Reed, Amy E., Ghoussaini, Maya, Carroll, Jason S., Jiang, Xia, Finucane, Hilary, Adams, Marcia, Adank, Muriel A., Ahsan, Habibul, Aittomäki, Kristiina, Anton-Culver, Hoda, Antonenkova, Natalia N., Arndt, Volker, Aronson, Kristan J., Arun, Banu, Auer, Paul L., Bacot, François, Barrdahl, Myrto, Baynes, Caroline, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bernstein, Leslie, Blomqvist, Carl, Bogdanova, Natalia V., Bojesen, Stig E., Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Brand, Judith S., Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Brinton, Louise, Broberg, Per, Brock, Ian W., Broeks, Annegien, Brooks-Wilson, Angela, Brucker, Sara Y., Brüning, Thomas, Burwinkel, Barbara, Butterbach, Katja, Cai, Qiuyin, Cai, Hui, Caldés, Trinidad, Canzian, Federico, Carracedo, Angel, Carter, Brian D., Castelao, Jose E., Chan, Tsun L., David Cheng, Ting-Yuan, Seng Chia, Kee, Choi, Ji-Yeob, Christiansen, Hans, Clarke, Christine L., Collée, Margriet, Conroy, Don M., Cordina-Duverger, Emilie, Cornelissen, Sten, Cox, David G., Cox, Angela, Cross, Simon S., Cunningham, Julie M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Doheny, Kimberly F., Dörk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Durcan, Lorraine, Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Eliassen, A. Heather, Ellberg, Carolina, Elvira, Mingajeva, Engel, Christoph, Eriksson, Mikael, Fasching, Peter A., Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Flyger, Henrik, Fritschi, Lin, Gaborieau, Valerie, Gabrielson, Marike, Gago-Dominguez, Manuela, Gao, Yu-Tang, Gapstur, Susan M., García-Sáenz, José A., Gaudet, Mia M., Georgoulias, Vassilios, Giles, Graham G., Glendon, Gord, Goldberg, Mark S., Goldgar, David E., González-Neira, Anna, Grenaker Alnæs, Grethe I., Grip, Mervi, Gronwald, Jacek, Grundy, Anne, Guénel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Håkansson, Niclas, Hamann, Ute, Hamel, Nathalie, Hankinson, Susan, Harrington, Patricia, Hart, Steven N., Hartikainen, Jaana M., Hartman, Mikael, Hein, Alexander, Heyworth, Jane, Hicks, Belynda, Hillemanns, Peter, Ho, Dona N., Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Hou, Ming-Feng, Hsiung, Chia-Ni, Huang, Guanmengqian, Humphreys, Keith, Ishiguro, Junko, Ito, Hidemi, Iwasaki, Motoki, Iwata, Hiroji, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Johnson, Nichola, Jones, Kristine, Jones, Michael, Jukkola-Vuorinen, Arja, Kaaks, Rudolf, Kabisch, Maria, Kaczmarek, Katarzyna, Kang, Daehee, Kasuga, Yoshio, Kerin, Michael J., Khan, Sofia, Khusnutdinova, Elza, Kiiski, Johanna I., Kim, Sung-Won, Knight, Julia A., Kosma, Veli-Matti, Kristensen, Vessela N., Krüger, Ute, Kwong, Ava, Lambrechts, Diether, Le Marchand, Loic, Lee, Eunjung, Lee, Min Hyuk, Lee, Jong Won, Neng Lee, Chuen, Lejbkowicz, Flavio, Li, Jingmei, Lilyquist, Jenna, Lindblom, Annika, Lissowska, Jolanta, Lo, Wing-Yee, Loibl, Sibylle, Long, Jirong, Lophatananon, Artitaya, Lubinski, Jan, Luccarini, Craig, Lux, Michael P., Ma, Edmond S. K., MacInnis, Robert J., Maishman, Tom, Makalic, Enes, Malone, Kathleen E., Kostovska, Ivana Maleva, Mannermaa, Arto, Manoukian, Siranoush, Manson, JoAnn E., Margolin, Sara, Mariapun, Shivaani, Martinez, Maria Elena, Matsuo, Keitaro, Mavroudis, Dimitrios, McKay, James, McLean, Catriona, Meijers-Heijboer, Hanne, Meindl, Alfons, Menéndez, Primitiva, Menon, Usha, Meyer, Jeffery, Miao, Hui, Miller, Nicola, Taib, Nur Aishah Mohd, Muir, Kenneth, Mulligan, Anna Marie, Mulot, Claire, Neuhausen, Susan L., Nevanlinna, Heli, Neven, Patrick, Nielsen, Sune F., Noh, Dong-Young, Nordestgaard, Børge G., Norman, Aaron, Olopade, Olufunmilayo I., Olson, Janet E., Olsson, Håkan, Olswold, Curtis, Orr, Nick, Pankratz, V. Shane, Park, Sue K., Park-Simon, Tjoung-Won, Lloyd, Rachel, Perez, Jose I. A., Peterlongo, Paolo, Peto, Julian, Phillips, Kelly-Anne, Pinchev, Mila, Plaseska-Karanfilska, Dijana, Prentice, Ross, Presneau, Nadege, Prokofyeva, Darya, Pugh, Elizabeth, Pylkäs, Katri, Rack, Brigitte, Radice, Paolo, Rahman, Nazneen, Rennert, Gadi, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Romm, Jane, Ruddy, Kathryn J., Rüdiger, Thomas, Rudolph, Anja, Ruebner, Matthias, Rutgers, Emiel J. T., Saloustros, Emmanouil, Sandler, Dale P., Sangrajrang, Suleeporn, Sawyer, Elinor J., Schmidt, Daniel F., Schmutzler, Rita K., Schneeweiss, Andreas, Schoemaker, Minouk J., Schumacher, Fredrick, Schürmann, Peter, Scott, Rodney J., Scott, Christopher, Seal, Sheila, Seynaeve, Caroline, Shah, Mitul, Sharma, Priyanka, Shen, Chen-Yang, Sheng, Grace, Sherman, Mark E., Shrubsole, Martha J., Shu, Xiao-Ou, Smeets, Ann, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Stegmaier, Christa, Stewart-Brown, Sarah, Stone, Jennifer, Stram, Daniel O., Surowy, Harald, Swerdlow, Anthony, Tamimi, Rulla, Taylor, Jack A., Tengström, Maria, Teo, Soo H., Beth Terry, Mary, Tessier, Daniel C., Thanasitthichai, Somchai, Thöne, Kathrin, Tollenaar, Rob A. E. M., Tomlinson, Ian, Tong, Ling, Torres, Diana, Truong, Thérèse, Tseng, Chiu-Chen, Tsugane, Shoichiro, Ulmer, Hans-Ulrich, Ursin, Giske, Untch, Michael, Vachon, Celine, van Asperen, Christi J., Van Den Berg, David, van den Ouweland, Ans M. W., van der Kolk, Lizet, van der Luijt, Rob B., Vincent, Daniel, Vollenweider, Jason, Waisfisz, Quinten, Wang-Gohrke, Shan, Weinberg, Clarice R., Wendt, Camilla, Whittemore, Alice S., Wildiers, Hans, Willett, Walter, Winqvist, Robert, Wolk, Alicja, Wu, Anna H., Xia, Lucy, Yamaji, Taiki, Yang, Xiaohong R., Har Yip, Cheng, Yoo, Keun-Young, Yu, Jyh-Cherng, Zheng, Wei, Zheng, Ying, Zhu, Bin, Ziogas, Argyrios, Ziv, Elad, Lakhani, Sunil R., Antoniou, Antonis C., Droit, Arnaud, Andrulis, Irene L., Amos, Christopher I., Couch, Fergus J., Pharoah, Paul D. P., Chang-Claude, Jenny, Hall, Per, Hunter, David J., Milne, Roger L., García-Closas, Montserrat, Schmidt, Marjanka K., Chanock, Stephen J., Dunning, Alison M., Edwards, Stacey L., Bader, Gary D., Chenevix-Trench, Georgia, Simard, Jacques, Kraft, Peter, and Easton, Douglas F.

Published
2017
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37. Common genetic variations in telomere length genes and lung cancer: a Mendelian randomisation study and its novel application in lung tumour transcriptome.

Author

Cardoso Penha, Ricardo Cortez, Smith-Byrne, Karl, Atkins, Joshua R., Haycock, Philip C., Kar, Siddhartha, Codd, Veryan, Samani, Nilesh J., Nelson, Christopher, Milojevic, Maja, Gabriel, Aurélie A. G., Amos, Christopher, Brennan, Paul, Hung, Rayjean J., Kachuri, Linda, and Mckay, James D.

Published
2023
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38. Identification of Novel Genetic Markers of Breast Cancer Survival

Author

Guo, Qi, Schmidt, Marjanka K., Kraft, Peter, Canisius, Sander, Chen, Constance, Khan, Sofia, Tyrer, Jonathan, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Michailidou, Kyriaki, Lush, Michael, Kar, Siddhartha, Beesley, Jonathan, Dunning, Alison M., Shah, Mitul, Czene, Kamila, Darabi, Hatef, Eriksson, Mikael, Lambrechts, Diether, Weltens, Caroline, Leunen, Karin, Bojesen, Stig E., Nordestgaard, Børge G., Nielsen, Sune F., Flyger, Henrik, Chang-Claude, Jenny, Rudolph, Anja, Seibold, Petra, Flesch-Janys, Dieter, Blomqvist, Carl, Aittomäki, Kristiina, Fagerholm, Rainer, Muranen, Taru A., Couch, Fergus J., Olson, Janet E., Vachon, Celine, Andrulis, Irene L., Knight, Julia A., Glendon, Gord, Mulligan, Anna Marie, Broeks, Annegien, Hogervorst, Frans B., Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick, Le Marchand, Loic, Hopper, John L., Tsimiklis, Helen, Apicella, Carmel, Southey, Melissa C., Cox, Angela, Cross, Simon S., Reed, Malcolm W. R., Giles, Graham G., Milne, Roger L., McLean, Catriona, Winqvist, Robert, Pylkäs, Katri, Jukkola-Vuorinen, Arja, Grip, Mervi, Hooning, Maartje J., Hollestelle, Antoinette, Martens, John W. M., van den Ouweland, Ans M. W., Marme, Federik, Schneeweiss, Andreas, Yang, Rongxi, Burwinkel, Barbara, Figueroa, Jonine, Chanock, Stephen J., Lissowska, Jolanta, Sawyer, Elinor J., Tomlinson, Ian, Kerin, Michael J., Miller, Nicola, Brenner, Hermann, Dieffenbach, Aida Karina, Arndt, Volker, Holleczek, Bernd, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M., Li, Jingmei, Brand, Judith S., Humphreys, Keith, Devilee, Peter, Tollenaar, Rob A. E. M., Seynaeve, Caroline, Radice, Paolo, Peterlongo, Paolo, Bonanni, Bernardo, Mariani, Paolo, Fasching, Peter A., Beckmann, Matthias W., Hein, Alexander, Ekici, Arif B., Chenevix-Trench, Georgia, Balleine, Rosemary, Phillips, Kelly-Anne, Benitez, Javier, Zamora, M. Pilar, Arias Perez, Jose Ignacio, Menéndez, Primitiva, Jakubowska, Anna, Lubinski, Jan, Jaworska-Bieniek, Katarzyna, Durda, Katarzyna, Hamann, Ute, Kabisch, Maria, Ulmer, Hans Ulrich, Rüdiger, Thomas, Margolin, Sara, Kristensen, Vessela, Nord, Silje, Evans, D. Gareth, Abraham, Jean E., Earl, Helena M., Hiller, Louise, Dunn, Janet A., Bowden, Sarah, Berg, Christine, Campa, Daniele, Diver, W. Ryan, Gapstur, Susan M., Gaudet, Mia M., Hankinson, Susan E., Hoover, Robert N., Hüsing, Anika, Kaaks, Rudolf, Machiela, Mitchell J., Willett, Walter, Barrdahl, Myrto, Canzian, Federico, Chin, Suet-Feung, Caldas, Carlos, Hunter, David J., Lindstrom, Sara, García-Closas, Montserrat, Hall, Per, Easton, Douglas F., Eccles, Diana M., Rahman, Nazneen, Nevanlinna, Heli, and Pharoah, Paul D. P.

Published
2015
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39. Morning chronotype and digestive tract cancers: Mendelian randomization study.

Author

Yuan, Shuai, Mason, Amy M., Titova, Olga E., Vithayathil, Mathew, Kar, Siddhartha, Chen, Jie, Li, Xue, Burgess, Stephen, and Larsson, Susanna C.

Subjects
ALIMENTARY canal, BILIARY tract, STOMACH cancer, COLORECTAL cancer, BODY mass index
Abstract

Morning chronotype has been associated with a reduced risk of prostate and breast cancer. However, few studies have examined whether chronotype is associated with digestive tract cancer risk. We conducted a Mendelian randomization (MR) study to assess the associations of chronotype with major digestive tract cancers. A total of 317 independent genetic variants associated with chronotype at the genome‐wide significance level (P < 5 × 10−8) were used as instrumental variables from a genome‐wide meta‐analysis of 449 734 individuals. Summary‐level data on overall and six digestive tract cancers, including esophageal, stomach, liver, biliary tract, pancreatic and colorectal cancers, were obtained from the UK Biobank (11 952 cases) and FinnGen (7638 cases) study. Genetic liability to morning chronotype was associated with reduced risk of overall digestive tract cancer and cancers of stomach, biliary tract and colorectum in UK Biobank. The associations for the overall digestive tract, stomach and colorectal cancers were directionally replicated in FinnGen. In the meta‐analysis of the two sources, genetic liability to morning chronotype was associated with a decreased risk of overall digestive tract cancer (odds ratio [OR] 0.94, 95% confidence interval [CI]: 0.90‐0.98), stomach cancer (OR 0.84, 95% CI: 0.73‐0.97) and colorectal cancer (OR 0.92, 95% CI: 0.87‐0.98), but not with the other studied cancers. The associations were consistent in multivariable MR analysis with adjustment for genetically predicted sleep duration, short sleep, insomnia and body mass index. The study provided MR evidence of inverse associations of morning chronotype with digestive tract cancer, particularly stomach and colorectal cancers. [ABSTRACT FROM AUTHOR]

Published
2023
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41. Circulating vitamin C and digestive system cancers: Mendelian randomization study.

Author

Larsson, Susanna C., Mason, Amy M., Vithayathil, Mathew, Carter, Paul, Kar, Siddhartha, Zheng, Ju-Sheng, and Burgess, Stephen

Abstract

Vitamin C is an antioxidant with a potential role in the prevention of digestive system cancers, but there is yet no consensus whether vitamin C has a causal role in these cancers. The aim of this study was to utilize Mendelian randomization to decipher the potential causal associations of vitamin C with risk of digestive system cancers. Ten genetic variants previously found to be significantly associated with circulating vitamin C were used as instrumental variables. Effect size estimates for the genetic associations of the vitamin C-associated genetic variants with six major malignancies of digestive system were obtained from the FinnGen (N = 309 154) and UK Biobank (N = 367 542) studies. Results from the two studies were combined using meta-analysis. Genetically predicted higher circulating vitamin C showed a suggestive association with lower risk of small intestine and colorectal cancer after accounting for multiple testing. The odds ratio per 1 standard deviation increment in circulating vitamin C was 0.55 (95% confidence interval 0.32–0.94; P = 0.029) for small intestine cancer and 0.84 (95% confidence interval 0.73–0.96; P = 0.013) for colorectal cancer. There was a suggestive association between genetically predicted higher circulating vitamin C with lower risk of liver cancer in FinnGen but no association in the meta-analysis (odds ratio 0.69; 95% CI 0.36–1.32; P = 0.265). Genetically predicted circulating vitamin C was not associated with cancers of the esophagus, stomach, or pancreas. This Mendelian randomization study indicates that vitamin C might play a role in the prevention of small intestine and colorectal cancer. [ABSTRACT FROM AUTHOR]

Published
2022
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46. Selenium and cancer risk: Wide‐angled Mendelian randomization analysis.

Author

Yuan, Shuai, Mason, Amy M., Carter, Paul, Vithayathil, Mathew, Kar, Siddhartha, Burgess, Stephen, and Larsson, Susanna C.

Subjects
DISEASE risk factors, SELENIUM, SINGLE nucleotide polymorphisms, RENAL cancer, LINKAGE disequilibrium
Abstract

Evidence on the association between selenium and cancer risk is inconclusive. We conducted a Mendelian randomization study to examine the associations of selenium levels with 22 site‐specific cancers and any cancer. Single nucleotide polymorphisms (SNPs) strongly associated with toenail and blood (TAB) and blood selenium levels in mild linkage disequilibrium (r2 <.3) were used as instrumental variables. Genetic associations of selenium‐associated SNPs with cancer were obtained from the UK Biobank including a total of 59 647 cancer cases and 307 914 controls. Associations with P <.1 in UK Biobank were tested for replication in the FinnGen consortium comprising more than 180 000 individuals. The inverse‐variance weighted method accounting for linkage disequilibrium was used to estimate the associations. Genetically predicted TAB selenium levels were not associated with the risk of the 22 site‐specific cancers or any cancer (all 22 site‐specific cancers). Similarly, we observed no strong association for genetically predicted blood selenium levels. However, genetically predicted blood selenium levels showed suggestive associations with risk of kidney cancer (odds ratio [OR] per one‐unit increase in log‐transformed levels: 0.83; 95% confidence interval [CI]: 0.67‐1.03) and multiple myeloma (OR: 1.40; 95% CI: 1.02‐1.93). The same direction of association for kidney cancer but not for multiple myeloma was observed in FinnGen. In the metaanalysis of UK Biobank and FinnGen, the OR of kidney cancer was 0.83 (95% CI: 0.69‐1.00). Our study suggests that high selenium status may not prevent cancer development. The associations for kidney cancer and multiple myeloma need to be verified in well‐powered studies. [ABSTRACT FROM AUTHOR]

Published
2022
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49. Serum Estradiol and 20 Site-Specific Cancers in Women: Mendelian Randomization Study.

Author

Larsson, Susanna C., Kar, Siddhartha, Perry, John R. B., Carter, Paul, Vithayathil, Mathew, Mason, Amy M., Easton, Douglas F., and Burgess, Stephen

Subjects
ESTRADIOL, ENDOMETRIAL cancer, CANCER risk factors
Abstract

Context: The causal role of endogenous estradiol in cancers other than breast and endometrial cancer remains unclear. Objective: This Mendelian randomization study assessed the causal associations of endogenous 17β-estradiol (E2), the most potent estrogen, with cancer risk in women. Methods: As primary genetic instrument, we used a genetic variant in the CYP19A1 gene that is strongly associated with serum E2 levels. Summary statistics genetic data for the association of the E2 variant with breast, endometrial, and ovarian cancer were obtained from large-scale consortia. We additionally estimated the associations of the E2 variant with any and 20 site-specific cancers in 198 825 women of European descent in UK Biobank. Odds ratios (OR) of cancer per 0.01 unit increase in log-transformed serum E2 levels in pmol/L were estimated using the Wald ratio. Results: Genetic predisposition to higher serum E2 levels was associated with increased risk of estrogen receptor (ER)-positive breast cancer (OR 1.02; 95% CI, 1.01-1.03; P = 2.5 × 10−3), endometrial cancer overall (OR 1.09; 95% CI, 1.06-1.11; P = 7.3 × 10−13), and endometrial cancer of the endometrioid histology subtype (OR 1.10; 95% CI, 1.07-1.13; P = 2.1 × 10−11). There were suggestive associations with breast cancer overall (OR 1.01; 95% CI, 1.00-1.02; P = 0.02), ovarian cancer of the endometrioid subtype (OR 1.05; 95% CI, 1.01-1.10; P = 0.02), and stomach cancer (OR 1.12; 95% CI, 1.00-1.26; P = 0.05), but no significant association with other cancers. Conclusion: This study supports a role of E2 in the development of ER-positive breast cancer and endometrioid endometrial cancer but found no strong association with other cancers in women. [ABSTRACT FROM AUTHOR]

Published
2022
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50. Do sex hormones confound or mediate the effect of chronotype on breast and prostate cancer? A Mendelian randomization study.

Author

Hayes, Bryony L., Robinson, Timothy, Kar, Siddhartha, Ruth, Katherine S., Tsilidis, Konstantinos K., Frayling, Timothy, Murray, Anna, Martin, Richard M., Lawlor, Deborah A., and Richmond, Rebecca C.

Subjects
SEX hormones, PROSTATE cancer, BIOAVAILABILITY, BREAST cancer, GENOME-wide association studies, BREAST, DISEASE risk factors
Abstract

Morning-preference chronotype has been found to be protective against breast and prostate cancer. Sex hormones have been implicated in relation to chronotype and the development of both cancers. This study aimed to assess whether sex hormones confound or mediate the effect of chronotype on breast and prostate cancer using a Mendelian Randomization (MR) framework. Genetic variants associated with chronotype and sex hormones (total testosterone, bioavailable testosterone, sex hormone binding globulin, and oestradiol) (p<5×10−8) were obtained from published genome-wide association studies (n≤244,207 females and n≤205,527 males). These variants were used to investigate causal relationships with breast (nCases/nControls = 133,384/113,789) and prostate (nCases/nControls = 79,148/61,106) cancer using univariable, bidirectional and multivariable MR. In females, we found evidence for: I) Reduced risk of breast cancer per category increase in morning-preference (OR = 0.93, 95% CI:0. 88, 1.00); II) Increased risk of breast cancer per SD increase in bioavailable testosterone (OR = 1.10, 95% CI: 1.01, 1.19) and total testosterone (OR = 1.15, 95% CI:1.07, 1.23); III) Bidirectional effects between morning-preference and both bioavailable and total testosterone (e.g. mean SD difference in bioavailable testosterone = -0.08, 95% CI:-0.12, -0.05 per category increase in morning-preference vs difference in morning-preference category = -0.04, 95% CI: -0.08, 0.00 per SD increase in bioavailable testosterone). In males, we found evidence for: I) Reduced risk of prostate cancer per category increase in morning-preference (OR = 0.90, 95% CI: 0.83, 0.97) and II) Increased risk of prostate cancer per SD increase in bioavailable testosterone (OR = 1.22, 95% CI: 1.08, 1.37). No bidirectional effects were found between morning-preference and testosterone in males. While testosterone levels were causally implicated with both chronotype and cancer, there was inconsistent evidence for testosterone as a mediator of the relationship. The protective effect of morning-preference on both breast and prostate cancer is clinically interesting, although it may be difficult to effectively modify chronotype. Further studies are needed to investigate other potentially modifiable intermediates. Author summary: Although previous studies have demonstrated that morning-preference chronotype is associated with reduced breast and prostate cancer risk, the role of sex hormones in this relationship has yet to be elucidated. In this study we use genetic variants strongly associated with morning-preference chronotype, total testosterone, bioavailable testosterone, sex-hormone binding globulin and oestradiol to explore the potential of these sex hormones to act as either mediators or confounders of this relationship. The findings of this study implicate testosterone as a potential mediator of the relationship between chronotype and both prostate and breast cancer risk, although results were inconsistent between methods. As such, further studies are warranted to better understand the mechanisms underlying this relationship in order to inform the development of sleep-based intervention studies that may help to reduce breast and prostate cancer risk in high-risk populations. [ABSTRACT FROM AUTHOR]

Published
2022
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