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1. Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes

Author

Chen, Zhishan, Guo, Xingyi, Tao, Ran, Huyghe, Jeroen R., Law, Philip J., Fernandez-Rozadilla, Ceres, Ping, Jie, Jia, Guochong, Long, Jirong, Li, Chao, Shen, Quanhu, Xie, Yuhan, Timofeeva, Maria N., Thomas, Minta, Schmit, Stephanie L., Díez-Obrero, Virginia, Devall, Matthew, Moratalla-Navarro, Ferran, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah E. W., Svinti, Victoria, Donnelly, Kevin, Farrington, Susan M., Blackmur, James, Vaughan-Shaw, Peter G., Shu, Xiao-Ou, Lu, Yingchang, Broderick, Peter, Studd, James, Harrison, Tabitha A., Conti, David V., Schumacher, Fredrick R., Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun-Seog, Shin, Min-Ho, Shin, Aesun, Ahn, Yoon-Ok, Kim, Dong-Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu-Tang, Jia, Wei-Hua, Hopper, John L., Jenkins, Mark A., Win, Aung Ko, Pai, Rish K., Figueiredo, Jane C., Haile, Robert W., Gallinger, Steven, Woods, Michael O., Newcomb, Polly A., Duggan, David, Cheadle, Jeremy P., Kaplan, Richard, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Jukka-Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri A., Rissanen, Harri, Pukkala, Eero, Eriksson, Johan G., Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie J., Ruiz-Narvaez, Edward, Palmer, Julie R., Buchanan, Daniel D., Platz, Elizabeth A., Visvanathan, Kala, Ulrich, Cornelia M., Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter T., Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha L., Potter, John D., Tsilidis, Kostas K., Schulze, Matthias B., Gunter, Marc J., Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Bishop, D. Timothy, Giles, Graham G., Southey, Melissa C., Idos, Gregory E., McDonnell, Kevin J., Abu-Ful, Zomoroda, Greenson, Joel K., Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu-Ru, Steinfelder, Robert, Keku, Temitope O., van Guelpen, Bethany, Hudson, Thomas J., Hampel, Heather, Pearlman, Rachel, Berndt, Sonja I., Hayes, Richard B., Martinez, Marie Elena, Thomas, Sushma S., Pharoah, Paul D. P., Larsson, Susanna C., Yen, Yun, Lenz, Heinz-Josef, White, Emily, Li, Li, Doheny, Kimberly F., Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew T., Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David J., Joshi, Amit D., Schafmayer, Clemens, Scacheri, Peter C., Kundaje, Anshul, Schoen, Robert E., Hampe, Jochen, Stadler, Zsofia K., Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Edlund, Christopher K., Gauderman, W. James, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen J., van Duijnhoven, Franzel, Feskens, Edith J. M., Sakoda, Lori C., Gago-Dominguez, Manuela, Wolk, Alicja, Pardini, Barbara, FitzGerald, Liesel M., Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie A., Kooperberg, Charles, Li, Christopher I., Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Le Marchand, Loic, Wu, Anna H., Qu, Chenxu, McNeil, Caroline E., Coetzee, Gerhard, Hayward, Caroline, Deary, Ian J., Harris, Sarah E., Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Lau, Ken S., Zhao, Hongyu, Hsu, Li, Cai, Qiuyin, Dunlop, Malcolm G., Gruber, Stephen B., Houlston, Richard S., Moreno, Victor, Casey, Graham, Peters, Ulrike, Tomlinson, Ian, and Zheng, Wei

Published
2024
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3. Impact of microsatellite status in early-onset colonic cancer.

Author

Zaborowski, Alexandra M, Adamina, Ahmed Abdile Michel, Aigner, Felix, d'Allens, Laura, Allmer, Caterina, Álvarez, Andrea, Anula, Rocio, Andric, Mihailo, Bach, Sam Atallah Simon, Bala, Miklosh, Barussaud, Marie, Bausys, Augustinas, Beggs, Andrew, Bellolio, Felipe, Bennett, Melissa-Rose, Berdinskikh, Anton, Bevan, Vicki, Biondo, Sebastiano, Bislenghi, Gabriele, Bludau, Marc, Brouwer, Nelleke, Brown, Carl, Bruns, Christiane, Buchanan, Daniel D, Buchwald, Pamela, Burger, Jacobus WA, Burlov, Nikita, Campanelli, Michela, Capdepont, Maylis, Carvello, Michele, Chew, Hwee-Hoon, Christoforidis, Dimitri, Clark, David, Climent, Marta, Collinson, Rowan, Cologne, Kyle G, Contreras, Tomas, Croner, Roland, Daniels, Ian R, Dapri, Giovanni, Davies, Justin, Delrio, Paolo, Denost, Quentin, Deutsch, Michael, Dias, Andre, D’Hoore, André, Drozdov, Evgeniy, Duek, Daniel, Dunlop, Malcolm, Dziki, Adam, Edmundson, Aleksandra, Efetov, Sergey, El-Hussuna, Alaa, Elliot, Brodie, Emile, Sameh, Espin, Eloy, Evans, Martyn, Faes, Seraina, Faiz, Omar, Figueiredo, Nuno, Fleming, Fergal, Foppa, Caterina, Fowler, George, Frasson, Matteo, Forgan, Tim, Frizelle, Frank, Gadaev, Shamil, Gellona, Jose, Glyn, Tamara, Goran, Barisic, Greenwood, Emma, Guren, Marianne G, Guillon, Stephanie, Gutlic, Ida, Hahnloser, Dieter, Hampel, Heather, Hanly, Ann, Hasegawa, Hirotoshi, Iversen, Lene Hjerrild, Hill, Andrew, Hill, James, Hoch, Jiri, Hompes, Roel, Hurtado, Luis, Iaquinandi, Fabiano, Imbrasaite, Ugne, Islam, Rumana, Jafari, Mehrenah D, Salido, Andrea Jiménez, Jiménez-Toscano, Marta, Kanemitsu, Yukihide, Karachun, Aleksei, Karimuddin, Ahmer A, Keller, Deborah S, Kelly, Justin, Kennelly, Rory, Khrykov, Gleb, Kocian, Peter, Koh, Cherry, and Kok, Neils

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Genetic Testing, Digestive Diseases, Genetics, Clinical Research, Colo-Rectal Cancer, Aetiology, 2.1 Biological and endogenous factors, Colonic Neoplasms, Colorectal Neoplasms, Humans, Microsatellite Instability, Microsatellite Repeats, Mutation, Prognosis, Proto-Oncogene Proteins B-raf, Proto-Oncogene Proteins p21(ras), REACCT Collaborative, Medical and Health Sciences, Surgery, Clinical sciences
Abstract

BackgroundThe molecular profile of early-onset colonic cancer is undefined. This study evaluated clinicopathological features and oncological outcomes of young patients with colonic cancer according to microsatellite status.MethodsAnonymized data from an international collaboration were analysed. Criteria for inclusion were patients younger than 50 years diagnosed with stage I-III colonic cancer that was surgically resected. Clinicopathological features, microsatellite status, and disease-specific outcomes were evaluated.ResultsA total of 650 patients fulfilled the criteria for inclusion. Microsatellite instability (MSI) was identified in 170 (26.2 per cent), whereas 480 had microsatellite-stable (MSS) tumours (relative risk of MSI 2.5 compared with older patients). MSI was associated with a family history of colorectal cancer and lesions in the proximal colon. The proportions with pathological node-positive disease (45.9 versus 45.6 per cent; P = 1.000) and tumour budding (20.3 versus 20.5 per cent; P = 1.000) were similar in the two groups. Patients with MSI tumours were more likely to have BRAF (22.5 versus 6.9 per cent; P < 0.001) and KRAS (40.0 versus 24.2 per cent; P = 0.006) mutations, and a hereditary cancer syndrome (30.0 versus 5.0 per cent; P < 0.001; relative risk 6). Five-year disease-free survival rates in the MSI group were 95.0, 92.0, and 80.0 per cent for patients with stage I, II, and III tumours, compared with 88.0, 88.0, and 65.0 per cent in the MSS group (P = 0.753, P = 0.487, and P = 0.105 respectively).ConclusionPatients with early-onset colonic cancer have a high risk of MSI and defined genetic conditions. Those with MSI tumours have more adverse pathology (budding, KRAS/BRAF mutations, and nodal metastases) than older patients with MSI cancers.

Published
2022

4. Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

Author

Thomas, Minta, Su, Yu-Ru, Rosenthal, Elisabeth A., Sakoda, Lori C., Schmit, Stephanie L., Timofeeva, Maria N., Chen, Zhishan, Fernandez-Rozadilla, Ceres, Law, Philip J., Murphy, Neil, Carreras-Torres, Robert, Diez-Obrero, Virginia, van Duijnhoven, Franzel J. B., Jiang, Shangqing, Shin, Aesun, Wolk, Alicja, Phipps, Amanda I., Burnett-Hartman, Andrea, Gsur, Andrea, Chan, Andrew T., Zauber, Ann G., Wu, Anna H., Lindblom, Annika, Um, Caroline Y., Tangen, Catherine M., Gignoux, Chris, Newton, Christina, Haiman, Christopher A., Qu, Conghui, Bishop, D. Timothy, Buchanan, Daniel D., Crosslin, David R., Conti, David V., Kim, Dong-Hyun, Hauser, Elizabeth, White, Emily, Siegel, Erin, Schumacher, Fredrick R., Rennert, Gad, Giles, Graham G., Hampel, Heather, Brenner, Hermann, Oze, Isao, Oh, Jae Hwan, Lee, Jeffrey K., Schneider, Jennifer L., Chang-Claude, Jenny, Kim, Jeongseon, Huyghe, Jeroen R., Zheng, Jiayin, Hampe, Jochen, Greenson, Joel, Hopper, John L., Palmer, Julie R., Visvanathan, Kala, Matsuo, Keitaro, Matsuda, Koichi, Jung, Keum Ji, Li, Li, Le Marchand, Loic, Vodickova, Ludmila, Bujanda, Luis, Gunter, Marc J., Matejcic, Marco, Jenkins, Mark A., Slattery, Martha L., D’Amato, Mauro, Wang, Meilin, Hoffmeister, Michael, Woods, Michael O., Kim, Michelle, Song, Mingyang, Iwasaki, Motoki, Du, Mulong, Udaltsova, Natalia, Sawada, Norie, Vodicka, Pavel, Campbell, Peter T., Newcomb, Polly A., Cai, Qiuyin, Pearlman, Rachel, Pai, Rish K., Schoen, Robert E., Steinfelder, Robert S., Haile, Robert W., Vandenputtelaar, Rosita, Prentice, Ross L., Küry, Sébastien, Castellví-Bel, Sergi, Tsugane, Shoichiro, Berndt, Sonja I., Lee, Soo Chin, Brezina, Stefanie, Weinstein, Stephanie J., Chanock, Stephen J., Jee, Sun Ha, Kweon, Sun-Seog, Vadaparampil, Susan, Harrison, Tabitha A., Yamaji, Taiki, Keku, Temitope O., Vymetalkova, Veronika, Arndt, Volker, Jia, Wei-Hua, Shu, Xiao-Ou, Lin, Yi, Ahn, Yoon-Ok, Stadler, Zsofia K., Van Guelpen, Bethany, Ulrich, Cornelia M., Platz, Elizabeth A., Potter, John D., Li, Christopher I., Meester, Reinier, Moreno, Victor, Figueiredo, Jane C., Casey, Graham, Lansdorp Vogelaar, Iris, Dunlop, Malcolm G., Gruber, Stephen B., Hayes, Richard B., Pharoah, Paul D. P., Houlston, Richard S., Jarvik, Gail P., Tomlinson, Ian P., Zheng, Wei, Corley, Douglas A., Peters, Ulrike, and Hsu, Li

Published
2023
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5. Author Correction: Application of Mendelian randomization to explore the causal role of the human gut microbiome in colorectal cancer

Author

Hatcher, Charlie, Richenberg, George, Waterson, Samuel, Nguyen, Long H., Joshi, Amit D., Carreras-Torres, Robert, Moreno, Victor, Chan, Andrew T., Gunter, Marc, Lin, Yi, Qu, Conghui, Song, Mingyang, Casey, Graham, Figueiredo, Jane C., Gruber, Stephen B., Hampe, Jochen, Hampel, Heather, Jenkins, Mark A., Keku, Temitope O., Peters, Ulrike, Tangen, Catherine M., Wu, Anna H., Hughes, David A., Rühlemann, Malte C., Raes, Jeroen, Timpson, Nicholas J., and Wade, Kaitlin H.

Published
2023
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6. Application of Mendelian randomization to explore the causal role of the human gut microbiome in colorectal cancer

Author

Hatcher, Charlie, Richenberg, George, Waterson, Samuel, Nguyen, Long H., Joshi, Amit D., Carreras-Torres, Robert, Moreno, Victor, Chan, Andrew T., Gunter, Marc, Lin, Yi, Qu, Conghui, Song, Mingyang, Casey, Graham, Figueiredo, Jane C., Gruber, Stephen B., Hampe, Jochen, Hampel, Heather, Jenkins, Mark A., Keku, Temitope O., Peters, Ulrike, Tangen, Catherine M., Wu, Anna H., Hughes, David A., Rühlemann, Malte C., Raes, Jeroen, Timpson, Nicholas J., and Wade, Kaitlin H.

Published
2023
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7. Post-Operative Functional Outcomes in Early Age Onset Rectal Cancer

Author

Collaborative, REACCT, O’Connell, Lauren V, Zaborowski, Alexandra M, Abdile, Ahmed, Adamina, Michel, Aigner, Felix, d’Allens, Laura, Allmer, Caterina, Álvarez, Andrea, Anula, Rocio, Andric, Mihailo, Bach, Sam Atallah Simon, Bala, Miklosh, Barussaud, Marie, Bausys, Augustinas, Beggs, Andrew, Bellolio, Felipe, Bennett, Melissa-Rose, Bevan, Vicki, Biondo, Sebastiano, Bislenghi, Gabriele, Bludau, Marc, Brown, Carl, Bruns, Christiane, Buchanan, Daniel D, Buchwald, Pamela, Burger, Jacobus WA, Burlov, Nikita, Campanelli, Michela, Capdepont, Maylis, Carvello, Michele, Chew, Hwee-Hoon, Christoforidis, Dimitri, Clark, David, Climent, Marta, Collinson, Rowan, Cologne, Kyle G, Contreras, Tomas, Croner, Roland, Daniels, Ian R, Dapri, Giovanni, Davies, Justin, Delrio, Paolo, Denost, Quentin, Deutsch, Michael, Dias, Andre, D’Hoore, André, Drozdov, Evgeniy, Duek, Daniel, Dunlop, Malcolm, Dziki, Adam, Edmundson, Aleksandra, Efetov, Sergey, El-Hussuna, Alaa, Elliott, Brodie, Emile, Sameh, Espin-Basany, Eloy, Evans, Martyn, Faes, Seraina, Faiz, Omar, Figueiredo, Nuno, Fleming, Fergal, Foppa, Caterina, Fowler, George, Frasson, Matteo, Forgan, Tim, Frizelle, Frank, Gadaev, Shamil, Gellona, Jose, Glyn, Tamara, Goran, Barisic, Greenwood, Emma, Guren, Marianne G, Guillon, Stephanie, Gutlic, Ida, Hahnloser, Dieter, Hampel, Heather, Hanly, Ann, Hasegawa, Hirotoshi, Iversen, Lene Hjerrild, Hill, Andrew, Hill, James, Hoch, Jiri, Hompes, Roel, Hurtado, Luis, Iaquinandi, Fabiano, Imbrasaite, Ugne, Islam, Rumana, Jafari, Mehrenah D, Salido, Andrea Jiménez, Jiménez-Toscano, Marta, Kanemitsu, Yukihide, Karachun, Aleksei, Karimuddin, Ahmer A, Keller, Deborah S, Kelly, Justin, Kennelly, Rory, Khrykov, Gleb, Kocian, Petr, and Koh, Cherry

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Rehabilitation, Cancer, Clinical Research, Digestive Diseases, Good Health and Well Being, REACCT Collaborative, early onset rectal cancer, functional outcome, patient reported outcome, rectal cancer, young rectal cancer, Clinical sciences, Oncology and carcinogenesis
Abstract

BackgroundImpairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (

Published
2022

8. Characteristics of Early-Onset vs Late-Onset Colorectal Cancer

Author

Collaborative, REACCT, Zaborowski, Alexandra M, Abdile, Ahmed, Adamina, Michel, Aigner, Felix, d’Allens, Laura, Allmer, Caterina, Álvarez, Andrea, Anula, Rocio, Andric, Mihailo, Atallah, Sam, Bach, Simon, Bala, Miklosh, Barussaud, Marie, Bausys, Augustinas, Bebington, Brendan, Beggs, Andrew, Bellolio, Felipe, Bennett, Melissa-Rose, Berdinskikh, Anton, Bevan, Vicki, Biondo, Sebastiano, Bislenghi, Gabriele, Bludau, Marc, Boutall, Adam, Brouwer, Nelleke, Brown, Carl, Bruns, Christiane, Buchanan, Daniel D, Buchwald, Pamela, Burger, Jacobus WA, Burlov, Nikita, Campanelli, Michela, Capdepont, Maylis, Carvello, Michele, Chew, Hwee-Hoon, Christoforidis, Dimitri, Clark, David, Climent, Marta, Cologne, Kyle G, Contreras, Tomas, Croner, Roland, Daniels, Ian R, Dapri, Giovanni, Davies, Justin, Delrio, Paolo, Denost, Quentin, Deutsch, Michael, Dias, Andre, D’Hoore, André, Drozdov, Evgeniy, Duek, Daniel, Dunlop, Malcolm, Dziki, Adam, Edmundson, Aleksandra, Efetov, Sergey, El-Hussuna, Alaa, Elliot, Brodie, Emile, Sameh, Espin, Eloy, Evans, Martyn, Faes, Seraina, Faiz, Omar, Fleming, Fergal, Foppa, Caterina, Fowler, George, Frasson, Matteo, Figueiredo, Nuno, Forgan, Tim, Frizelle, Frank, Gadaev, Shamil, Gellona, Jose, Glyn, Tamara, Gong, Jianping, Goran, Barisic, Greenwood, Emma, Guren, Marianne G, Guillon, Stephanie, Gutlic, Ida, Hahnloser, Dieter, Hampel, Heather, Hanly, Ann, Hasegawa, Hirotoshi, Iversen, Lene Hjerrild, Hill, Andrew, Hill, James, Hoch, Jiri, Hoffmeister, Michael, Hompes, Roel, Hurtado, Luis, Iaquinandi, Fabiano, Imbrasaite, Ugne, Islam, Rumana, Jafari, Mehrenah Dorna, Kanemitsu, Yukihide, Karachun, Aleksei, Karimuddin, Ahmer A, Keller, Deborah S, Kelly, Justin, and Kennelly, Rory

Subjects
Aging, Nutrition, Digestive Diseases, Cancer, Colo-Rectal Cancer, Genetics, Clinical Research, Prevention, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Adult, Age of Onset, Colorectal Neoplasms, Humans, Incidence, Middle Aged, Risk Factors, REACCT Collaborative
Abstract

ImportanceThe incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer.ObservationsWithin the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts.Conclusions and relevanceThe clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

Published
2021

9. Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance

Author

Durno, Carol, Ercan, Ayse Bahar, Bianchi, Vanessa, Edwards, Melissa, Aronson, Melyssa, Galati, Melissa, Atenafu, Eshetu G, Abebe-Campino, Gadi, Al-Battashi, Abeer, Alharbi, Musa, Azad, Vahid Fallah, Baris, Hagit N, Basel, Donald, Bedgood, Raymond, Bendel, Anne, Ben-Shachar, Shay, Blumenthal, Deborah T, Blundell, Maude, Bornhorst, Miriam, Bronsema, Annika, Cairney, Elizabeth, Rhode, Sara, Caspi, Shani, Chamdin, Aghiad, Chiaravalli, Stefano, Constantini, Shlomi, Crooks, Bruce, Das, Anirban, Dvir, Rina, Farah, Roula, Foulkes, William D, Frenkel, Zehavit, Gallinger, Bailey, Gardner, Sharon, Gass, David, Ghalibafian, Mithra, Gilpin, Catherine, Goldberg, Yael, Goudie, Catherine, Hamid, Syed Ahmer, Hampel, Heather, Hansford, Jordan R, Harlos, Craig, Hijiya, Nobuko, Hsu, Saunders, Kamihara, Junne, Kebudi, Rejin, Knipstein, Jeffrey, Koschmann, Carl, Kratz, Christian, Larouche, Valerie, Lassaletta, Alvaro, Lindhorst, Scott, Ling, Simon C, Link, Michael P, De Mola, Rebecca Loret, Luiten, Rebecca, Lurye, Michal, Maciaszek, Jamie L, MagimairajanIssai, Vanan, Maher, Ossama M, Massimino, Maura, McGee, Rose B, Mushtaq, Naureen, Mason, Gary, Newmark, Monica, Nicholas, Garth, Nichols, Kim E, Nicolaides, Theodore, Opocher, Enrico, Osborn, Michael, Oshrine, Benjamin, Pearlman, Rachel, Pettee, Daniel, Rapp, Jan, Rashid, Mohsin, Reddy, Alyssa, Reichman, Lara, Remke, Marc, Robbins, Gabriel, Roy, Sumita, Sabel, Magnus, Samuel, David, Scheers, Isabelle, Schneider, Kami Wolfe, Sen, Santanu, Stearns, Duncan, Sumerauer, David, Swallow, Carol, Taylor, Leslie, Thomas, Gregory, Toledano, Helen, Tomboc, Patrick, Van Damme, An, Winer, Ira, Yalon, Michal, Yen, Lee Yi, Zapotocky, Michal, Zelcer, Shayna, and Ziegler, David S

Subjects
Cancer, Brain Disorders, Clinical Research, Digestive Diseases, Prevention, Brain Cancer, Rare Diseases, Adolescent, Adult, Brain Neoplasms, Child, Child, Preschool, Colorectal Neoplasms, DNA Mismatch Repair, DNA Repair Enzymes, Early Detection of Cancer, Female, Follow-Up Studies, Humans, Male, Neoplastic Syndromes, Hereditary, Population Surveillance, Prognosis, Prospective Studies, Survival Rate, United States, Young Adult, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposeConstitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals.Patients and methodsData were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation.ResultsA total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically (P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively (P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance (P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years.ConclusionSurveillance and early cancer detection are associated with improved OS for individuals with CMMRD.

Published
2021

10. Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review.

Author

REACCT Collaborative, Zaborowski, Alexandra M, Abdile, Ahmed, Adamina, Michel, Aigner, Felix, d'Allens, Laura, Allmer, Caterina, Álvarez, Andrea, Anula, Rocio, Andric, Mihailo, Atallah, Sam, Bach, Simon, Bala, Miklosh, Barussaud, Marie, Bausys, Augustinas, Bebington, Brendan, Beggs, Andrew, Bellolio, Felipe, Bennett, Melissa-Rose, Berdinskikh, Anton, Bevan, Vicki, Biondo, Sebastiano, Bislenghi, Gabriele, Bludau, Marc, Boutall, Adam, Brouwer, Nelleke, Brown, Carl, Bruns, Christiane, Buchanan, Daniel D, Buchwald, Pamela, Burger, Jacobus WA, Burlov, Nikita, Campanelli, Michela, Capdepont, Maylis, Carvello, Michele, Chew, Hwee-Hoon, Christoforidis, Dimitri, Clark, David, Climent, Marta, Cologne, Kyle G, Contreras, Tomas, Croner, Roland, Daniels, Ian R, Dapri, Giovanni, Davies, Justin, Delrio, Paolo, Denost, Quentin, Deutsch, Michael, Dias, Andre, D'Hoore, André, Drozdov, Evgeniy, Duek, Daniel, Dunlop, Malcolm, Dziki, Adam, Edmundson, Aleksandra, Efetov, Sergey, El-Hussuna, Alaa, Elliot, Brodie, Emile, Sameh, Espin, Eloy, Evans, Martyn, Faes, Seraina, Faiz, Omar, Fleming, Fergal, Foppa, Caterina, Fowler, George, Frasson, Matteo, Figueiredo, Nuno, Forgan, Tim, Frizelle, Frank, Gadaev, Shamil, Gellona, Jose, Glyn, Tamara, Gong, Jianping, Goran, Barisic, Greenwood, Emma, Guren, Marianne G, Guillon, Stephanie, Gutlic, Ida, Hahnloser, Dieter, Hampel, Heather, Hanly, Ann, Hasegawa, Hirotoshi, Iversen, Lene Hjerrild, Hill, Andrew, Hill, James, Hoch, Jiri, Hoffmeister, Michael, Hompes, Roel, Hurtado, Luis, Iaquinandi, Fabiano, Imbrasaite, Ugne, Islam, Rumana, Jafari, Mehrenah Dorna, Kanemitsu, Yukihide, Karachun, Aleksei, Karimuddin, Ahmer A, Keller, Deborah S, Kelly, Justin, and Kennelly, Rory

Subjects
REACCT Collaborative
Abstract

ImportanceThe incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer.ObservationsWithin the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts.Conclusions and relevanceThe clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

Published
2021

12. Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

Author

Fernandez-Rozadilla, Ceres, Timofeeva, Maria, Chen, Zhishan, Law, Philip, Thomas, Minta, Schmit, Stephanie, Díez-Obrero, Virginia, Hsu, Li, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah, Svinti, Victoria, Donnelly, Kevin, Farrington, Susan, Blackmur, James, Vaughan-Shaw, Peter, Shu, Xiao-ou, Long, Jirong, Cai, Qiuyin, Guo, Xingyi, Lu, Yingchang, Broderick, Peter, Studd, James, Huyghe, Jeroen, Harrison, Tabitha, Conti, David, Dampier, Christopher, Devall, Mathew, Schumacher, Fredrick, Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Moratalla-Navarro, Ferran, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun-Seog, Shin, Min-Ho, Shin, Aesun, Ahn, Yoon-Ok, Kim, Dong-Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu-Tang, Jia, Wei-Hua, Hopper, John, Jenkins, Mark, Win, Aung Ko, Pai, Rish, Figueiredo, Jane, Haile, Robert, Gallinger, Steven, Woods, Michael, Newcomb, Polly, Duggan, David, Cheadle, Jeremy, Kaplan, Richard, Maughan, Timothy, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Lukka-Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri, Rissanen, Harri, Pukkala, Eero, Eriksson, Johan, Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Zanke, Brent, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie, Ruiz-Narvaez, Edward, Palmer, Julie, Buchanan, Daniel, Platz, Elizabeth, Visvanathan, Kala, Ulrich, Cornelia, Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter, Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha, Potter, John, Tsilidis, Konstantinos, Schulze, Matthias, Gunter, Marc, Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Stern, Mariana, Pardamean, Bens, Bishop, Timothy, Giles, Graham, Southey, Melissa, Idos, Gregory, McDonnell, Kevin, Abu-Ful, Zomoroda, Greenson, Joel, Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu-Ru, Steinfelder, Robert, Keku, Temitope, van Guelpen, Bethany, Hudson, Thomas, Hampel, Heather, Pearlman, Rachel, Berndt, Sonja, Hayes, Richard, Martinez, Marie Elena, Thomas, Sushma, Corley, Douglas, Pharoah, Paul, Larsson, Susanna, Yen, Yun, Lenz, Heinz-Josef, White, Emily, Li, Li, Doheny, Kimberly, Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew, Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David, Joshi, Amit, Schafmayer, Clemens, Scacheri, Peter, Kundaje, Anshul, Nickerson, Deborah, Schoen, Robert, Hampe, Jochen, Stadler, Zsofia, Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Papadopoulos, Nickolas, Edlund, Chistopher, Gauderman, William, Thomas, Duncan, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen, van Duijnhoven, Franzel, Feskens, Edith, Sakoda, Lori, Gago-Dominguez, Manuela, Wolk, Alicja, Naccarati, Alessio, Pardini, Barbara, FitzGerald, Liesel, Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie, Kooperberg, Charles, Li, Christopher, Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Tangen, Catherine, Mardis, Elaine, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Haiman, Christopher, Le Marchand, Loic, Wu, Anna, Qu, Chenxu, McNeil, Caroline, Coetzee, Gerhard, Hayward, Caroline, Deary, Ian, Harris, Sarah, Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Moreno, Victor, Casey, Graham, Gruber, Stephen, Tomlinson, Ian, Zheng, Wei, Dunlop, Malcolm, Houlston, Richard, and Peters, Ulrike

Published
2023
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15. Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study

Author

Tsilidis, Konstantinos K, Papadimitriou, Nikos, Dimou, Niki, Gill, Dipender, Lewis, Sarah J, Martin, Richard M, Murphy, Neil, Markozannes, Georgios, Zuber, Verena, Cross, Amanda J, Burrows, Kimberley, Lopez, David S, Key, Timothy J, Travis, Ruth C, Perez-Cornago, Aurora, Hunter, David J, van Duijnhoven, Fränzel JB, Albanes, Demetrius, Arndt, Volker, Berndt, Sonja I, Bézieau, Stéphane, Bishop, D Timothy, Boehm, Juergen, Brenner, Hermann, Burnett-Hartman, Andrea, Campbell, Peter T, Casey, Graham, Castellví-Bel, Sergi, Chan, Andrew T, Chang-Claude, Jenny, de la Chapelle, Albert, Figueiredo, Jane C, Gallinger, Steven J, Giles, Graham G, Goodman, Phyllis J, Gsur, Andrea, Hampe, Jochen, Hampel, Heather, Hoffmeister, Michael, Jenkins, Mark A, Keku, Temitope O, Kweon, Sun-Seog, Larsson, Susanna C, Le Marchand, Loic, Li, Christopher I, Li, Li, Lindblom, Annika, Martín, Vicente, Milne, Roger L, Moreno, Victor, Nan, Hongmei, Nassir, Rami, Newcomb, Polly A, Offit, Kenneth, Pharoah, Paul DP, Platz, Elizabeth A, Potter, John D, Qi, Lihong, Rennert, Gad, Sakoda, Lori C, Schafmayer, Clemens, Slattery, Martha L, Snetselaar, Linda, Schenk, Jeanette, Thibodeau, Stephen N, Ulrich, Cornelia M, Van Guelpen, Bethany, Harlid, Sophia, Visvanathan, Kala, Vodickova, Ludmila, Wang, Hansong, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Zheng, Wei, Bueno-de-Mesquita, Bas, Boutron-Ruault, Marie-Christine, Hughes, David J, Jakszyn, Paula, Kühn, Tilman, Palli, Domenico, Riboli, Elio, Giovannucci, Edward L, Banbury, Barbara L, Gruber, Stephen B, Peters, Ulrike, Gunter, Marc J, and on behalf of GECCO, CORECT

Subjects
Complementary and Integrative Health, Digestive Diseases, Clinical Research, Clinical Trials and Supportive Activities, Cancer, Colo-Rectal Cancer, Prevention, Nutrition, Prevention of disease and conditions, and promotion of well-being, 3.3 Nutrition and chemoprevention, Case-Control Studies, Colorectal Neoplasms, Dietary Supplements, Genetic Predisposition to Disease, Humans, Mendelian Randomization Analysis, Micronutrients, Risk Factors, Selenium, Vitamin B 12, White People, Mendelian randomization, genes, nutrition, supplements, colorectal cancer, Engineering, Medical and Health Sciences, Nutrition & Dietetics
Abstract

BackgroundThe literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.ObjectivesTo complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR).MethodsTwo-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.ResultsNominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.ConclusionsThese results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.

Published
2021

16. Elucidating the Risk of Colorectal Cancer for Variants in Hereditary Colorectal Cancer Genes

Author

Wang, Xiaoliang, Huyghe, Jeroen R., Joo, Jihoon E., Georgeson, Peter, Arndt, Volker, Berndt, Sonja I., Bézieau, Stéphane, Bien, Stephanie A., Bishop, D. Timothy, Brenner, Hermann, Brezina, Stefanie, Burnett-Hartman, Andrea, Campbell, Peter T., Casey, Graham, Castellví-Bel, Sergi, Chan, Andrew T., Chang-Claude, Jenny, Chen, Xuechen, Conti, David V., Cremolini, Chiara, Diergaarde, Brenda, Figueiredo, Jane C., FitzGerald, Liesel M., Gago-Dominguez, Manuela, Gallinger, Steven, Giles, Graham G., Gsu, Andrea, Gunter, Marc J., Hampe, Jochen, Hampel, Heather, Harrison, Tabitha A., Hoffmeister, Michael, Keku, Temitope O., Kundaje, Anshul, Le Marchand, Loic, Lenz, Heinz-Josef, Li, Christopher I., Li, Li, Lin, Yi, Lindblom, Annika, Moreno, Victor, Murphy, Neil, Newcomb, Polly A., Newton, Christina C., Obón-Santacana, Mireia, Ogino, Shuji, Pai, Rish K., Palmer, Julie R., Pearlman, Rachel, Pharoah, Paul D.P., Phipps, Amanda I., Platz, Elizabeth A., Potter, John D., Rennert, Gad, Sakoda, Lori C., Schafmayer, Clemens, Schmit, Stephanie L., Schoen, Robert E., Slattery, Martha L., Stadler, Zsofia K., Steinfelder, Robert S., Thibodeau, Stephen N., Ulrich, Cornelia M., Um, Caroline Y., van Duijnhoven, Franzel J.B., Van Guelpen, Bethany, Visvanathan, Kala, Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Weinstein, Stephanie J., White, Emily, Winship, Ingrid M., Wolk, Alicja, Gruber, Stephen B., Jenkins, Mark A., Mahmood, Khalid, Thomas, Minta, Qu, Conghui, Hsu, Li, Buchanan, Daniel D., and Peters, Ulrike

Published
2023
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17. Double somatic mismatch repair gene pathogenic variants as common as Lynch syndrome among endometrial cancer patients

Author

Hampel, Heather, Pearlman, Rachel, de la Chapelle, Albert, Pritchard, Colin C, Zhao, Weiqiang, Jones, Dan, Yilmaz, Ahmet, Chen, Wei, Frankel, Wendy L, Suarez, Adrian A, Cosgrove, Casey, Backes, Floor, Copeland, Larry, Fowler, Jeffrey, O'Malley, David, Salani, Ritu, McElroy, Joseph P, Stanich, Peter P, Goodfellow, Paul, and Cohn, David E

Subjects
Rare Diseases, Clinical Research, Genetics, Digestive Diseases, Colo-Rectal Cancer, Cancer, Aetiology, 2.1 Biological and endogenous factors, Adult, Aged, Aged, 80 and over, Colorectal Neoplasms, Hereditary Nonpolyposis, DNA Methylation, DNA Mismatch Repair, Endometrial Neoplasms, Female, Germ-Line Mutation, Humans, Middle Aged, MutL Protein Homolog 1, Neoplasm Staging, Young Adult, Endometrial, Neoplasm, Mismatch repair, Lynch syndrome, Somatic, Double somatic, Oncology and Carcinogenesis, Paediatrics and Reproductive Medicine, Oncology & Carcinogenesis
Abstract

ObjectiveLynch syndrome is the most common cause of inherited endometrial cancer, attributable to germline pathogenic variants (PV) in mismatch repair (MMR) genes. Tumor microsatellite instability (MSI-high) and MMR IHC abnormalities are characteristics of Lynch syndrome. Double somatic MMR gene PV also cause MSI-high endometrial cancers. The aim of this study was to determine the relative frequency of Lynch syndrome and double somatic MMR PV.Methods341 endometrial cancer patients enrolled in the Ohio Colorectal Cancer Prevention Initiative at The Ohio State University Comprehensive Cancer Center from 1/1/13-12/31/16. All tumors underwent immunohistochemical (IHC) staining for the four MMR proteins, MSI testing, and MLH1 methylation testing if the tumor was MMR-deficient (dMMR). Germline genetic testing for Lynch syndrome was undertaken for all cases with dMMR tumors lacking MLH1 methylation. Tumor sequencing followed if a germline MMR gene PV was not identified.ResultsTwenty-seven percent (91/341) of tumors were either MSI-high or had abnormal IHC indicating dMMR. As expected, most dMMR tumors had MLH1 methylation; (69, 75.8% of the dMMR cases; 20.2% of total). Among the 22 (6.5%) cases with dMMR not explained by methylation, 10 (2.9% of total) were found to have Lynch syndrome (6 MSH6, 3 MSH2, 1 PMS2). Double somatic MMR PV accounted for the remaining 12 dMMR cases (3.5% of total).ConclusionsSince double somatic MMR gene PV are as common as Lynch syndrome among endometrial cancer patients, paired tumor and germline testing for patients with non-methylated dMMR tumor may be the most efficient approach for LS screening.

Published
2021

18. Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy: Guideline From the College of American Pathologists in Collaboration With the Association for Molecular Pathology and Fight Colorectal Cancer

Author

Bartley, Angela N., Mills, Anne M., Konnick, Eric, Overman, Michael, Ventura, Christina B., Souter, Lesley, Colasacco, Carol, Stadler, Zsofia K., Kerr, Sarah, Howitt, Brooke E., Hampel, Heather, Adams, Sarah F., Johnson, Wenora, Magi-Galluzzi, Cristina, Sepulveda, Antonia R., and Broaddus, Russell R.

Subjects
Practice guidelines (Medicine) -- Evaluation, Colorectal cancer -- Care and treatment, Immunotherapy -- Testing, DNA mismatch repair -- Testing, Microsatellite instability -- Testing, Health
Abstract

* Context.--The US Food and Drug Administration (FDA) approved immune checkpoint inhibitor therapy for patients with advanced solid tumors that have DNA mismatch repair defects or high levels of microsatellite instability; however, the FDA provided no guidance on which specific clinical assays should be used to determine mismatch repair status. Objective.--To develop an evidence-based guideline to identify the optimal clinical laboratory test to identify defects in DNA mismatch repair in patients with solid tumor malignancies who are being considered for immune checkpoint inhibitor therapy. Design.--The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Using the National Academy of Medicine-endorsed Grading of Recommendations Assessment, Development and Evaluation approach, the recommendations were derived from available evidence, strength of that evidence, open comment feedback, and expert panel consensus. Mismatch repair immunohistochemistry, microsatellite instability derived from both polymerase chain reaction and next-generation sequencing, and tumor mutation burden derived from large panel next-generation sequencing were within scope. Results.--Six recommendations and 3 good practice statements were developed. More evidence and evidence of higher quality were identified for colorectal cancer and other cancers of the gastrointestinal (GI) tract than for cancers arising outside the GI tract. Conclusions.--An optimal assay depends on cancer type. For most cancer types outside of the GI tract and the endometrium, there was insufficient published evidence to recommend a specific clinical assay. Absent published evidence, immunohistochemistry is an acceptable approach readily available in most clinical laboratories. doi: 10.5858/arpa.2021-0632-CP, Clinical laboratory assays for detection of high levels of tumor microsatellite instability (MSI-High) or loss of DNA mismatch repair (MMR) protein expression by immunohistochemistry (IHC) are familiar to many pathologists [...]

Published
2022
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19. MLH1-methylated endometrial cancer under 60 years of age as the “sentinel” cancer in female carriers of high-risk constitutional MLH1 epimutation

Author

Hitchins, Megan P., Alvarez, Rocio, Zhou, Lisa, Aguirre, Francesca, Dámaso, Estela, Pineda, Marta, Capella, Gabriel, Wong, Justin J.-L., Yuan, Xiaopu, Ryan, Shawnia R., Sathe, Devika S., Baxter, Melanie D., Cannon, Timothy, Biswas, Rakesh, DeMarco, Tiffani, Grzelak, Doreen, Hampel, Heather, and Pearlman, Rachel

Published
2023
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20. Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines

Author

Cavestro, Giulia Martina, Mannucci, Alessandro, Balaguer, Francesc, Hampel, Heather, Kupfer, Sonia S., Repici, Alessandro, Sartore-Bianchi, Andrea, Seppälä, Toni T., Valentini, Vincenzo, Boland, Clement Richard, Brand, Randall E., Buffart, Tineke E., Burke, Carol A., Caccialanza, Riccardo, Cannizzaro, Renato, Cascinu, Stefano, Cercek, Andrea, Crosbie, Emma J., Danese, Silvio, Dekker, Evelien, Daca-Alvarez, Maria, Deni, Francesco, Dominguez-Valentin, Mev, Eng, Cathy, Goel, Ajay, Guillem, Josè G., Houwen, Britt B.S.L., Kahi, Charles, Kalady, Matthew F., Kastrinos, Fay, Kühn, Florian, Laghi, Luigi, Latchford, Andrew, Liska, David, Lynch, Patrick, Malesci, Alberto, Mauri, Gianluca, Meldolesi, Elisa, Møller, Pål, Monahan, Kevin J., Möslein, Gabriela, Murphy, Caitlin C., Nass, Karlijn, Ng, Kimmie, Oliani, Cristina, Papaleo, Enrico, Patel, Swati G., Puzzono, Marta, Remo, Andrea, Ricciardiello, Luigi, Ripamonti, Carla Ida, Siena, Salvatore, Singh, Satish K., Stadler, Zsofia K., Stanich, Peter P., Syngal, Sapna, Turi, Stefano, Urso, Emanuele Damiano, Valle, Laura, Vanni, Valeria Stella, Vilar, Eduardo, Vitellaro, Marco, You, Yi-Qian Nancy, Yurgelun, Matthew B., Zuppardo, Raffaella Alessia, and Stoffel, Elena M.

Published
2023
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21. The role of family history in predicting germline pathogenic variant carriers who develop pancreatic cancer: Results of a multicenter collaboration

Author

Karloski, Eve, primary, Dudley, Beth, additional, Diergaarde, Brenda, additional, Blanco, Amie, additional, Everett, Jessica N., additional, Levinson, Elana, additional, Rangarajan, Tara, additional, Stanich, Peter P., additional, Childers, Kimberly, additional, Brown, Sandra, additional, Drogan, Christine, additional, Cavestro, Giulia Martina, additional, Gordon, Kelly, additional, Singh, Aparajita, additional, Simeone, Diane M., additional, Reich, Hannah, additional, Kastrinos, Fay, additional, Zakalik, Dana, additional, Hampel, Heather, additional, Pearlman, Rachel, additional, Gordon, Ora K., additional, Kupfer, Sonia S., additional, Puzzono, Marta, additional, Zuppardo, Raffaella Alessia, additional, and Brand, Randall E., additional

Published
2024
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22. Association of ESR1 germline variants with TP53 somatic variants in breast tumors in a genome-wide study

Author

Tjader, Nijole P., primary, Beer, Abigail J., additional, Ramroop, Johnny, additional, Tai, Mei-Chee, additional, Ping, Jie, additional, Gandhi, Tanish, additional, Dauch, Cara, additional, Neuhausen, Susan L., additional, Ziv, Elad, additional, Sotelo, Nereida, additional, Ghanekar, Shreya, additional, Meadows, Owen, additional, Paredes, Monica, additional, Gillespie, Jessica L., additional, Aeilts, Amber M., additional, Hampel, Heather, additional, Zheng, Wei, additional, Jia, Guochong, additional, Hu, Qiang, additional, Wei, Lei, additional, Liu, Song, additional, Ambrosone, Christine B., additional, Palmer, Julie R., additional, Carpten, John D., additional, Yao, Song, additional, Stevens, Patrick, additional, Ho, Weang-Kee, additional, Pan, Jia Wern, additional, Fadda, Paolo, additional, Huo, Dezheng, additional, Teo, Soo Hwang, additional, McElroy, Joseph Paul, additional, and Toland, Amanda E., additional

Published
2024
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24. Methylated SEPTIN9 plasma test for colorectal cancer detection may be applicable to Lynch syndrome

Author

Hitchins, Megan P, Vogelaar, Ingrid P, Brennan, Kevin, Haraldsdottir, Sigurdis, Zhou, Nianmin, Martin, Brock, Alvarez, Rocio, Yuan, Xiaopu, Kim, Sungjin, Guindi, Maha, Hendifar, Andrew E, Kalady, Matthew F, DeVecchio, Jennifer, Church, James M, de la Chapelle, Albert, Hampel, Heather, Pearlman, Rachel, Christensen, Maria, Snyder, Carrie, Lanspa, Stephen J, Haile, Robert W, and Lynch, Henry T

Subjects
Public Health, Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Cancer, Rare Diseases, Clinical Research, Colo-Rectal Cancer, Prevention, Digestive Diseases, Genetics, Genetic Testing, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, 4.2 Evaluation of markers and technologies, SEPTIN9, circulating tumor dna, colorectal cancer, lynch syndrome, plasma, Clinical sciences, Public health
Abstract

ObjectiveThe plasma-based methylated SEPTIN9 (mSEPT9) is a colorectal cancer (CRC) screening test for adults aged 50-75 years who are at average risk for CRC and have refused colonoscopy or faecal-based screening tests. The applicability of mSEPT9 for high-risk persons with Lynch syndrome (LS), the most common hereditary CRC condition, has not been assessed. This study sought preliminary evidence for the utility of mSEPT9 for CRC detection in LS.DesignFirstly, SEPT9 methylation was measured in LS-associated CRC, advanced adenoma, and subject-matched normal colorectal mucosa tissues by pyrosequencing. Secondly, to detect mSEPT9 as circulating tumor DNA, the plasma-based mSEPT9 test was retrospectively evaluated in LS subjects using the Epi proColon 2.0 CE assay adapted for 1mL plasma using the "1/1 algorithm". LS case groups included 20 peri-surgical cases with acolonoscopy-based diagnosis of CRC (stages I-IV), 13 post-surgical metastatic CRC, and 17 pre-diagnosis cases. The control group comprised 31 cancer-free LS subjects.ResultsDifferential hypermethylation was found in 97.3% (36/37) of primary CRC and 90.0% (18/20) of advanced adenomas, showing LS-associated neoplasia frequently produce the mSEPT9 biomarker. Sensitivity of plasma mSEPT9 to detect CRC was 70.0% (95% CI, 48%-88%)in cases with a colonoscopy-based CRC diagnosis and 92.3% (95% CI, 64%-100%) inpost-surgical metastatic cases. In pre-diagnosis cases, plasma mSEPT9 was detected within two months prior to colonoscopy-based CRC diagnosis in 3/5 cases. Specificity in controls was 100% (95% CI 89%-100%).ConclusionThese preliminary findings suggest mSEPT9 may demonstrate similar diagnostic performance characteristics in LS as in the average-risk population, warranting a well-powered prospective case-control study.

Published
2019

26. Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Author

Møller, Pål, Seppälä, Toni, Dowty, James G., Haupt, Saskia, Dominguez-Valentin, Mev, Sunde, Lone, Bernstein, Inge, Engel, Christoph, Aretz, Stefan, Nielsen, Maartje, Capella, Gabriel, Evans, Dafydd Gareth, Burn, John, Holinski-Feder, Elke, Bertario, Lucio, Bonanni, Bernardo, Lindblom, Annika, Levi, Zohar, Macrae, Finlay, Winship, Ingrid, Plazzer, John-Paul, Sijmons, Rolf, Laghi, Luigi, Valle, Adriana Della, Heinimann, Karl, Half, Elizabeth, Lopez-Koestner, Francisco, Alvarez-Valenzuela, Karin, Scott, Rodney J., Katz, Lior, Laish, Ido, Vainer, Elez, Vaccaro, Carlos Alberto, Carraro, Dirce Maria, Gluck, Nathan, Abu-Freha, Naim, Stakelum, Aine, Kennelly, Rory, Winter, Des, Rossi, Benedito Mauro, Greenblatt, Marc, Bohorquez, Mabel, Sheth, Harsh, Tibiletti, Maria Grazia, Lino-Silva, Leonardo S., Horisberger, Karoline, Portenkirchner, Carmen, Nascimento, Ivana, Rossi, Norma Teresa, da Silva, Leandro Apolinário, Thomas, Huw, Zaránd, Attila, Mecklin, Jukka-Pekka, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepisto, Anna, Peltomäki, Päivi, Therkildsen, Christina, Lindberg, Lars Joachim, Thorlacius-Ussing, Ole, von Knebel Doeberitz, Magnus, Loeffler, Markus, Rahner, Nils, Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Hüneburg, Robert, de Vargas, Aída Falcón, Latchford, Andrew, Gerdes, Anne-Marie, Backman, Ann-Sofie, Guillén-Ponce, Carmen, Snyder, Carrie, Lautrup, Charlotte K., Amor, David, Palmero, Edenir, Stoffel, Elena, Duijkers, Floor, Hall, Michael J., Hampel, Heather, Williams, Heinric, Okkels, Henrik, Lubiński, Jan, Reece, Jeanette, Ngeow, Joanne, Guillem, Jose G., Arnold, Julie, Wadt, Karin, Monahan, Kevin, Senter, Leigha, Rasmussen, Lene J., van Hest, Liselotte P., Ricciardiello, Luigi, Kohonen-Corish, Maija R. J., Ligtenberg, Marjolijn J. L., Southey, Melissa, Aronson, Melyssa, Zahary, Mohd N., Samadder, N. Jewel, Poplawski, Nicola, Hoogerbrugge, Nicoline, Morrison, Patrick J., James, Paul, Lee, Grant, Chen-Shtoyerman, Rakefet, Ankathil, Ravindran, Pai, Rish, Ward, Robyn, Parry, Susan, Dębniak, Tadeusz, John, Thomas, van Overeem Hansen, Thomas, Caldés, Trinidad, Yamaguchi, Tatsuro, Barca-Tierno, Verónica, Garre, Pilar, Cavestro, Giulia Martina, Weitz, Jürgen, Redler, Silke, Büttner, Reinhard, Heuveline, Vincent, Hopper, John L., Win, Aung Ko, Lindor, Noralane, Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane, Buchanan, Daniel D., Thibodeau, Stephen N., ten Broeke, Sanne W., Hovig, Eivind, Nakken, Sigve, Pineda, Marta, Dueñas, Nuria, Brunet, Joan, Green, Kate, Lalloo, Fiona, Newton, Katie, Crosbie, Emma J., Mints, Miriam, Tjandra, Douglas, Neffa, Florencia, Esperon, Patricia, Kariv, Revital, Rosner, Guy, Pavicic, Walter Hernán, Kalfayan, Pablo, Torrezan, Giovana Tardin, Bassaneze, Thiago, Martin, Claudia, Moslein, Gabriela, Ahadova, Aysel, Kloor, Matthias, Sampson, Julian R., and Jenkins, Mark A.

Published
2022
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27. Author Correction: Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

Author

Fernandez-Rozadilla, Ceres, Timofeeva, Maria, Chen, Zhishan, Law, Philip, Thomas, Minta, Schmit, Stephanie, Díez-Obrero, Virginia, Hsu, Li, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah, Svinti, Victoria, Donnelly, Kevin, Farrington, Susan, Blackmur, James, Vaughan-Shaw, Peter, Shu, Xiao-ou, Long, Jirong, Cai, Qiuyin, Guo, Xingyi, Lu, Yingchang, Broderick, Peter, Studd, James, Huyghe, Jeroen, Harrison, Tabitha, Conti, David, Dampier, Christopher, Devall, Mathew, Schumacher, Fredrick, Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Moratalla-Navarro, Ferran, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun-Seog, Shin, Min-Ho, Shin, Aesun, Ahn, Yoon-Ok, Kim, Dong-Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu-Tang, Jia, Wei-Hua, Hopper, John, Jenkins, Mark, Win, Aung Ko, Pai, Rish, Figueiredo, Jane, Haile, Robert, Gallinger, Steven, Woods, Michael, Newcomb, Polly, Duggan, David, Cheadle, Jeremy, Kaplan, Richard, Maughan, Timothy, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Lukka-Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri, Rissanen, Harri, Pukkala, Eero, Eriksson, Johan, Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Zanke, Brent, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie, Ruiz-Narvaez, Edward, Palmer, Julie, Buchanan, Daniel, Platz, Elizabeth, Visvanathan, Kala, Ulrich, Cornelia, Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter, Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha, Potter, John, Tsilidis, Konstantinos, Schulze, Matthias, Gunter, Marc, Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Stern, Mariana, Pardamean, Bens, Bishop, Timothy, Giles, Graham, Southey, Melissa, Idos, Gregory, McDonnell, Kevin, Abu-Ful, Zomoroda, Greenson, Joel, Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu-Ru, Steinfelder, Robert, Keku, Temitope, van Guelpen, Bethany, Hudson, Thomas, Hampel, Heather, Pearlman, Rachel, Berndt, Sonja, Hayes, Richard, Martinez, Marie Elena, Thomas, Sushma, Corley, Douglas, Pharoah, Paul, Larsson, Susanna, Yen, Yun, Lenz, Heinz-Josef, White, Emily, Li, Li, Doheny, Kimberly, Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew, Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David, Joshi, Amit, Schafmayer, Clemens, Scacheri, Peter, Kundaje, Anshul, Nickerson, Deborah, Schoen, Robert, Hampe, Jochen, Stadler, Zsofia, Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Papadopoulos, Nickolas, Edlund, Chistopher, Gauderman, William, Thomas, Duncan, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen, van Duijnhoven, Franzel, Feskens, Edith, Sakoda, Lori, Gago-Dominguez, Manuela, Wolk, Alicja, Naccarati, Alessio, Pardini, Barbara, FitzGerald, Liesel, Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie, Kooperberg, Charles, Li, Christopher, Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Tangen, Catherine, Mardis, Elaine, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Haiman, Christopher, Le Marchand, Loic, Wu, Anna, Qu, Chenxu, McNeil, Caroline, Coetzee, Gerhard, Hayward, Caroline, Deary, Ian, Harris, Sarah, Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Moreno, Victor, Casey, Graham, Gruber, Stephen, Tomlinson, Ian, Zheng, Wei, Dunlop, Malcolm, Houlston, Richard, and Peters, Ulrike

Published
2023
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32. Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study

Author

Win, Aung Ko, Dowty, James G., Reece, Jeanette C., Lee, Grant, Templeton, Allyson S., Plazzer, John-Paul, Buchanan, Daniel D., Akagi, Kiwamu, Aksoy, Seçil, Alonso, Angel, Alvarez, Karin, Amor, David J., Ankathil, Ravindran, Aretz, Stefan, Arnold, Julie L., Aronson, Melyssa, Austin, Rachel, Backman, Ann-Sofie, Bajwa-ten Broeke, Sanne W., Barca-Tierno, Verónica, Barwell, Julian, Bernstein, Inge, Berthet, Pascaline, Betz, Beate, Bignon, Yves-Jean, Boisjoli, Talya, Bonadona, Valérie, Briollais, Laurent, Brunet, Joan, Bucksch, Karolin, Buecher, Bruno, Buettner, Reinhard, Burn, John, Caldés, Trinidad, Capella, Gabriel, Caron, Olivier, Casey, Graham, Chew, Min H., Choi, Yun-hee, Church, James, Clendenning, Mark, Colas, Chrystelle, Cops, Elisa J., Coupier, Isabelle, Cruz-Correa, Marcia, de la Chapelle, Albert, de Wind, Niels, Dębniak, Tadeusz, Della Valle, Adriana, Delnatte, Capuccine, Dhooge, Marion, Dominguez-Valentin, Mev, Drouet, Youenn, Duijkers, Floor A., Engel, Christoph, Esperon, Patricia, Evans, D. Gareth, Falcón de Vargas, Aída, Figueiredo, Jane C, Foulkes, William, Fourme, Emmanuelle, Frebourg, Thierry, Gallinger, Steven, Garre, Pilar, Genuardi, Maurizio, Gerdes, Anne-Marie, Gima, Lauren M., Giraud, Sophie, Goodwin, Annabel, Görgens, Heike, Green, Kate, Guillem, Jose, Guillén-Ponce, Carmen, Guimbaud, Roselyne, Guindalini, Rodrigo S.C., Half, Elizabeth E., Hall, Michael J, Hampel, Heather, Hansen, Thomas V.O., Heinimann, Karl, Hes, Frederik J., Hill, James, Ho, Judy W.C., Holinski-Feder, Elke, Hoogerbrugge, Nicoline, Hüneburg, Robert, Huntley, Vanessa, James, Paul A., Jensen, Uffe B, John, Thomas, Juhari, Wan K.W., Kalady, Matthew, Kastrinos, Fay, Kloor, Matthias, Kohonen-Corish, Maija RJ, Krogh, Lotte N., Kupfer, Sonia S., Ladabaum, Uri, Lagerstedt-Robinson, Kristina, Lalloo, Fiona, Lasset, Christine, Latchford, Andrew, Laurent-Puig, Pierre, Lautrup, Charlotte K., Leggett, Barbara A., Lejeune, Sophie, LeMarchand, Loic, Ligtenberg, Marjolijn, Lindor, Noralane, Loeffler, Markus, Longy, Michel, Lopez, Francisco, Lowery, Jan, Lubiński, Jan, Lucassen, Anneke M, Lynch, Patrick M., Malińska, Karolina, Matsubara, Nagahide, Mecklin, Jukka-Pekka, Møller, Pål, Monahan, Kevin, Morrison, Patrick J., Nattermann, Jacob, Navarro, Matilde, Neffa, Florencia, Neklason, Deborah, Newcomb, Polly A., Ngeow, Joanne, Nichols, Cassandra, Nielsen, Maartje, Nixon, Dawn M., Nogues, Catherine, Okkels, Henrik, Olschwang, Sylviane, Pachter, Nicholas, Pai, Rish K., Palmero, Edenir I., Pande, Mala, Parry, Susan, Patel, Swati G., Pearlman, Rachel, Perne, Claudia, Pineda, Marta, Poplawski, Nicola K, Pylvänäinen, Kirsi, Qiu, Jay, Rahner, Nils, Ramesar, Raj, Rasmussen, Lene J., Redler, Silke, Reis, Rui M., Ricciardiello, Luigi, Rogoża-Janiszewska, Emilia, Rosty, Christophe, Samadder, N. Jewel, Sampson, Julian R., Schackert, Hans K., Schmiegel, Wolff, Schulmann, Karsten, Schuster, Helène, Scott, Rodney, Senter, Leigha, Seppälä, Toni T, Shtoyerman, Rakefet, Sijmons, Rolf H., Snyder, Carrie, Solomon, Ilana B., Soto, Jose Luis, Southey, Melissa C., Spigelman, Allan, Spirandelli, Florencia, Spurdle, Amanda B., Steinke-Lange, Verena, Stoffel, Elena M., Strassburg, Christian P., Sunde, Lone, Susman, Rachel, Syngal, Sapna, Tanakaya, Kohji, Tezcan, Gülçin, Therkildsen, Christina, Thibodeau, Steve, Tomita, Naohiro, Tucker, Katherine M., Tunca, Berrin, Turchetti, Daniela, Uhrhammer, Nancy, Utsunomiya, Joji, Vaccaro, Carlos, van Duijnhoven, Fränzel J.B., van Wanzeele, Meghan J., Vangala, Deepak B., Vasen, Hans F.A., von Knebel Doeberitz, Magnus, von Salomé, Jenny, Wadt, Karin A.W., Ward, Robyn L., Weitz, Jürgen, Weitzel, Jeffrey N., Williams, Heinric, Winship, Ingrid, Wise, Paul E., Wods, Julie, Woods, Michael O., Yamaguchi, Tatsuro, Zachariae, Silke, Zahary, Mohd N., Hopper, John L., Haile, Robert W., Macrae, Finlay A., Möslein, Gabriela, and Jenkins, Mark A.

Published
2021
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33. Identifying Novel Susceptibility Genes for Colorectal Cancer Risk From a Transcriptome-Wide Association Study of 125,478 Subjects

Author

Guo, Xingyi, Lin, Weiqiang, Wen, Wanqing, Huyghe, Jeroen, Bien, Stephanie, Cai, Qiuyin, Harrison, Tabitha, Chen, Zhishan, Qu, Conghui, Bao, Jiandong, Long, Jirong, Yuan, Yuan, Wang, Fangqin, Bai, Mengqiu, Abecasis, Goncalo R., Albanes, Demetrius, Berndt, Sonja I., Bézieau, Stéphane, Bishop, D. Timothy, Brenner, Hermann, Buch, Stephan, Burnett-Hartman, Andrea, Campbell, Peter T., Castellví-Bel, Sergi, Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Cho, Sang Hee, Conti, David V., Chapelle, Albert de la, Feskens, Edith J.M., Gallinger, Steven J., Giles, Graham G., Goodman, Phyllis J., Gsur, Andrea, Guinter, Mark, Gunter, Marc J., Hampe, Jochen, Hampel, Heather, Hayes, Richard B., Hoffmeister, Michael, Kampman, Ellen, Kang, Hyun Min, Keku, Temitope O., Kim, Hyeong Rok, Le Marchand, Loic, Lee, Soo Chin, Li, Christopher I., Li, Li, Lindblom, Annika, Lindor, Noralane, Milne, Roger L., Moreno, Victor, Murphy, Neil, Newcomb, Polly A., Nickerson, Deborah A., Offit, Kenneth, Pearlman, Rachel, Pharoah, Paul D.P., Platz, Elizabeth A., Potter, John D., Rennert, Gad, Sakoda, Lori C., Schafmayer, Clemens, Schmit, Stephanie L., Schoen, Robert E., Schumacher, Fredrick R., Slattery, Martha L., Su, Yu-Ru, Tangen, Catherine M., Ulrich, Cornelia M., van Duijnhoven, Franzel J.B., Van Guelpen, Bethany, Visvanathan, Kala, Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Wang, Xiaoliang, White, Emily, Wolk, Alicja, Woods, Michael O., Casey, Graham, Hsu, Li, Jenkins, Mark A., Gruber, Stephen B., Peters, Ulrike, and Zheng, Wei

Published
2021
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34. Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Author

Maller, Pål, Seppälä, Toni, Dowty, James G., Haupt, Saskia, Dominguez-Valentin, Mev, Sunde, Lone, Bernstein, Inge, Engel, Christoph, Aretz, Stefan, Nielsen, Maartje, Capella, Gabriel, Evans, Dafydd Gareth, Burn, John, Holinski-Feder, Elke, Bertario, Lucio, Bonanni, Bernardo, Lindblom, Annika, Levi, Zohar, Macrae, Finlay, Winship, Ingrid, Plazzer, John-Paul, Sijmons, Rolf, Laghi, Luigi, Valle, Adriana Della, Heinimann, Karl, Half, Elizabeth, Lopez-Koestner, Francisco, Alvarez-Valenzuela, Karin, Scott, Rodney J., Katz, Lior, Laish, Ido, Vainer, Elez, Vaccaro, Carlos Alberto, Carraro, Dirce Maria, Gluck, Nathan, Abu-Freha, Naim, Stakelum, Aine, Kennelly, Rory, Winter, Des, Rossi, Benedito Mauro, Greenblatt, Marc, Bohorquez, Mabel, Sheth, Harsh, Tibiletti, Maria Grazia, Lino-Silva, Leonardo S., Horisberger, Karoline, Portenkirchner, Carmen, Nascimento, Ivana, Rossi, Norma Teresa, da Silva, Leandro Apolinário, Thomas, Huw, Zaránd, Attila, Mecklin, Jukka-Pekka, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepisto, Anna, Peltomäki, Päivi, Therkildsen, Christina, Lindberg, Lars Joachim, Thorlacius-Ussing, Ole, von Knebel Doeberitz, Magnus, Loeffler, Markus, Rahner, Nils, Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Hüneburg, Robert, de Vargas, Aída Falcón, Latchford, Andrew, Gerdes, Anne-Marie, Backman, Ann-Sofie, Guillén-Ponce, Carmen, Snyder, Carrie, Lautrup, Charlotte K., Amor, David, Palmero, Edenir, Stoffel, Elena, Duijkers, Floor, Hall, Michael J., Hampel, Heather, Williams, Heinric, Okkels, Henrik, LubiÅski, Jan, Reece, Jeanette, Ngeow, Joanne, Guillem, Jose G., Arnold, Julie, Wadt, Karin, Monahan, Kevin, Senter, Leigha, Rasmussen, Lene J., van Hest, Liselotte P., Ricciardiello, Luigi, Kohonen-Corish, Maija R. J., Ligtenberg, Marjolijn J. L., Southey, Melissa, Aronson, Melyssa, Zahary, Mohd N., Samadder, N. Jewel, Poplawski, Nicola, Hoogerbrugge, Nicoline, Morrison, Patrick J., James, Paul, Lee, Grant, Chen-Shtoyerman, Rakefet, Ankathil, Ravindran, Pai, Rish, Ward, Robyn, Parry, Susan, DÄbniak, Tadeusz, John, Thomas, van Overeem Hansen, Thomas, Caldés, Trinidad, Yamaguchi, Tatsuro, Barca-Tierno, Verónica, Garre, Pilar, Cavestro, Giulia Martina, Weitz, Jürgen, Redler, Silke, Büttner, Reinhard, Heuveline, Vincent, Hopper, John L., Win, Aung Ko, Lindor, Noralane, Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane, Buchanan, Daniel D., Thibodeau, Stephen N., ten Broeke, Sanne W., Hovig, Eivind, Nakken, Sigve, Pineda, Marta, Dueéas, Nuria, Brunet, Joan, Green, Kate, Lalloo, Fiona, Newton, Katie, Crosbie, Emma J., Mints, Miriam, Tjandra, Douglas, Neffa, Florencia, Esperon, Patricia, Kariv, Revital, Rosner, Guy, Pavicic, Walter Hernán, Kalfayan, Pablo, Torrezan, Giovana Tardin, Bassaneze, Thiago, Martin, Claudia, Moslein, Gabriela, Ahadova, Aysel, Kloor, Matthias, Sampson, Julian R., and Jenkins, Mark A.

Subjects
EPUB (Standard) -- Comparative analysis, Colonoscopy -- Comparative analysis, Colorectal cancer -- Comparative analysis, Health
Abstract

Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so. Keywords: Lynch Syndrome, Epidemiology, Prevention, Penetrance, Colorectal cancer, Segregation analysis, Prospective, Incidence, Over-diagnosis, Colonoscopy, Author(s): Pål Maller[sup.1], Toni Seppälä[sup.2,3,4], James G. Dowty[sup.5], Saskia Haupt[sup.6,7], Mev Dominguez-Valentin[sup.1], Lone Sunde[sup.8,9], Inge Bernstein[sup.10,11], Christoph Engel[sup.12], Stefan Aretz[sup.13], Maartje Nielsen[sup.14], Gabriel Capella[sup.15], Dafydd Gareth Evans[sup.16], John Burn[sup.17], Elke [...]

Published
2022
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35. The Evolution of Genetic Testing from Focused Testing to Panel Testing and from Patient Focused to Population Testing: Are We There Yet?

Author

Gima, Lauren, Solomon, Ilana, and Hampel, Heather

Abstract

The field of cancer genetics has evolved significantly over the past 30 years. Genetic testing has become less expensive and more comprehensive which has changed practice patterns. It is no longer necessary to restrict testing to those with the highest likelihood of testing positive. In addition, we have learned that the criteria developed to determine who has the highest likelihood of testing positive are neither sensitive nor specific. As a result, the field is moving from testing only the highest risk patients identified based on testing criteria to testing all cancer patients. This requires new service delivery models where testing can be mainstreamed into oncology clinics and posttest genetic counseling can be provided to individuals who test positive and those with concerning personal or family histories who test negative. The use of videos, testing kiosks, chatbots, and genetic counseling assistants have been employed to help facilitate testing at a larger scale and have good patient uptake and satisfaction. While testing is important for cancer patients as it may impact their treatment, future cancer risks, and family member's cancer risks, it is unfortunate that their cancer could not be prevented in the first place. Population testing for all adults would be a strategy to identify individuals with adult-onset diseases before they develop cancer in an attempt to prevent it entirely. A few research studies (Healthy Nevada and MyCode) have offered population testing for the three Centers for Disease Control and Prevention Tier 1 conditions: hereditary breast and ovarian cancer syndrome, Lynch syndrome, and familial hypercholesterolemia finding a prevalence of 1 in 70 individuals in the general population. We anticipate that testing for all cancer patients and the general population will continue to increase over the next 20 years and the genetics community needs to help lead the way to ensure this happens in a responsible manner. [ABSTRACT FROM AUTHOR]

Published
2024
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36. Association ofESR1germline variants withTP53somatic variants in breast tumors in a genome-wide study

Author

Tjader, Nijole P, primary, Beer, Abigail J, additional, Ramroop, Johnny, additional, Tai, Mei-Chee, additional, Ping, Jie, additional, Gandhi, Tanish, additional, Dauch, Cara, additional, Neuhausen, Susan L, additional, Ziv, Elad, additional, Sotelo, Nereida, additional, Ghanekar, Shreya, additional, Meadows, Owen, additional, Paredes, Monica, additional, Gillespie, Jessica, additional, Aeilts, Amber, additional, Hampel, Heather, additional, Zheng, Wei, additional, Jia, Guochong, additional, Hu, Qiang, additional, Wei, Lei, additional, Liu, Song, additional, Ambrosone, Christine B., additional, Palmer, Julie R., additional, Carpten, John D., additional, Yao, Song, additional, Stevens, Patrick, additional, Ho, Weang-Kee, additional, Pan, Jia Wern, additional, Fadda, Paolo, additional, Huo, Dezheng, additional, Teo, Soo-Hwang, additional, McElroy, Joesph Paul, additional, and Toland, Amanda Ewart, additional

Published
2023
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37. A Video Intervention to Improve Patient Understanding of Tumor Genomic Testing in Patients with Cancer

Author

Veney, Deloris, primary, Wei, Lai, additional, Toland, Amanda E., additional, Presley, Carolyn J., additional, Hampel, Heather, additional, Padamsee, Tasleem J., additional, Lee, Clara N., additional, Irvin, William J., additional, Bishop, Michael, additional, Kim, James, additional, Hovick, Shelly R., additional, Senter, Leigha, additional, and Stover, Daniel G., additional

Published
2023
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39. S318 Implementation of a Digital Cancer Risk Assessment Tool and Genetic Testing Program in Gastroenterology Practices Throughout the US Identifies Inherited Cancer Susceptibility Syndromes in 15.6% of Patients Tested

Author

Hampel, Heather, primary, Peterson, Candace, additional, Kieran, Shannon, additional, Pambianco, Daniel, additional, Amann, Stephen T., additional, Dickstein, George, additional, Molos, Mark A., additional, and Karlitz, Jordan J., additional

Published
2023
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40. Mutation Spectrum and Risk of Colorectal Cancer in African American Families with Lynch Syndrome

Author

Santa Cruz Guindalini, Rodrigo, Win, Aung Ko, Gulden, Cassandra, Lindor, Noralane M, Newcomb, Polly A, Haile, Robert W, Raymond, Victoria, Stoffel, Elena, Hall, Michael, Llor, Xavier, Ukaegbu, Chinedu I, Solomon, Ilana, Weitzel, Jeffrey, Kalady, Matthew, Blanco, Amie, Terdiman, Jonathan, Shuttlesworth, Gladis A, Lynch, Patrick M, Hampel, Heather, Lynch, Henry T, Jenkins, Mark A, Olopade, Olufunmilayo I, and Kupfer, Sonia S

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Nutrition and Dietetics, Digestive Diseases, Rare Diseases, Colo-Rectal Cancer, Cancer, Prevention, Clinical Research, Genetics, Genetic Testing, Aetiology, 2.1 Biological and endogenous factors, Adaptor Proteins, Signal Transducing, Adenosine Triphosphatases, Adult, Black or African American, Age Factors, Aged, Aged, 80 and over, Colorectal Neoplasms, Colorectal Neoplasms, Hereditary Nonpolyposis, DNA Mismatch Repair, DNA Repair Enzymes, DNA-Binding Proteins, Family, Female, Humans, Incidence, Male, Middle Aged, Mismatch Repair Endonuclease PMS2, MutL Protein Homolog 1, MutS Homolog 2 Protein, Mutation, Nuclear Proteins, Retrospective Studies, Risk Factors, Sex Factors, African Descent, Colon Cancer, DNA Repair, Hereditary Non-Polyposis Colorectal Cancer, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology, Clinical sciences, Nutrition and dietetics
Abstract

Background & aimsAfrican Americans (AAs) have the highest incidence of and mortality resulting from colorectal cancer (CRC) in the United States. Few data are available on genetic and nongenetic risk factors for CRC among AAs. Little is known about cancer risks and mutations in mismatch repair (MMR) genes in AAs with the most common inherited CRC condition, Lynch syndrome. We aimed to characterize phenotype, mutation spectrum, and risk of CRC in AAs with Lynch syndrome.MethodsWe performed a retrospective study of AAs with mutations in MMR genes (MLH1, MSH2, MSH6, and PMS2) using databases from 13 US referral centers. We analyzed data on personal and family histories of cancer. Modified segregation analysis conditioned on ascertainment criteria was used to estimate age- and sex-specific CRC cumulative risk, studying members of the mutation-carrying families.ResultsWe identified 51 AA families with deleterious mutations that disrupt function of the MMR gene product: 31 in MLH1 (61%), 11 in MSH2 (21%), 3 in MSH6 (6%), and 6 in PMS2 (12%); 8 mutations were detected in more than 1 individual, and 11 have not been previously reported. In the 920 members of the 51 families with deleterious mutations, the cumulative risks of CRC at 80 years of age were estimated to be 36.2% (95% confidence interval [CI], 10.5%-83.9%) for men and 29.7% (95% CI, 8.31%-76.1%) for women. CRC risk was significantly higher among individuals with mutations in MLH1 or MSH2 (hazard ratio, 13.9; 95% CI, 3.44-56.5).ConclusionsWe estimate the cumulative risk for CRC in AAs with MMR gene mutations to be similar to that of individuals of European descent with Lynch syndrome. Two-thirds of mutations were found in MLH1, some of which were found in multiple individuals and some that have not been previously reported. Differences in mutation spectrum are likely to reflect the genetic diversity of this population.

Published
2015

46. A Summary of the Fight Colorectal Cancer Working Meeting: Exploring Risk Factors and Etiology of Sporadic Early-Age Onset Colorectal Cancer

Author

Dwyer, Andrea J., Murphy, Caitlin C., Boland, C. Richard, Garcia, Reese, Hampel, Heather, Limburg, Paul, Lowery, Jan, Zauber, Ann G., Waring, Stephen, Worrall, Sharyn, Perea, Jose, Siegel, Rebecca, Lee, Jeffrey, Molmenti, Christine, Sears, Cynthia L., Buckhaults, Phillip, Hayes, Richard, Hussan, Hisham, de Miranda, Noel, Palles, Claire, Diaz, Luis, Song, Mingyang, Cercek, Andrea, Lieu, Christopher H., Patel, Swati G., Karlitz, Jordan J., Cao, Yin, Demb, Josh, Blatchford, Patrick, Risendal, Betsy, Staples, Elsa S., Wali, Anil, Daschner, Phil, Loomans-Kropp, Holli, Flores, R., Levell, Caleb L., Wehling, Karen, Martin, Jessica, Pesmen, Curt, Kuchar, Violet, Soisson, Ryan, Davis, Anjee, and Ahnen, Dennis

Published
2019
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49. Cascade testing for hereditary cancer: comprehensive multigene panels identify unexpected actionable findings in relatives.

Author

Heald, Brandie, Pirzadeh-Miller, Sara, Ellsworth, Rachel E, Nielsen, Sarah M, Russell, Emily M, Beitsch, Peter, Esplin, Edward D, Nussbaum, Robert L, Pineda-Alvarez, Daniel E, Kurian, Allison W, and Hampel, Heather

Subjects
CANCER genes, EARLY detection of cancer, RELATIVES, GENETIC variation, GERM cells
Abstract

Current guidelines recommend single variant testing in relatives of patients with known pathogenic or likely pathogenic germline variants in cancer predisposition genes. This approach may preclude the use of risk-reducing strategies in family members who have pathogenic or likely pathogenic germline variants in other cancer predisposition genes. Cascade testing using multigene panels was performed in 3696 relatives of 7433 probands. Unexpected pathogenic or likely pathogenic germline variants were identified in 230 (6.2%) relatives, including 144 who were negative for the familial pathogenic or likely pathogenic variant but positive for a pathogenic or likely pathogenic variant in a different gene than the proband and 74 who tested positive for the familial pathogenic or likely pathogenic variant and had an additional pathogenic or likely pathogenic variant in a different gene than the proband. Of the relatives with unexpected pathogenic or likely pathogenic germline variants, 36.3% would have qualified for different or additional cancer screening recommendations. Limiting cascade testing to only the familial pathogenic or likely pathogenic variant would have resulted in missed, actionable findings for a subset of relatives. [ABSTRACT FROM AUTHOR]

Published
2024
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