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1. 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 W. A., 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, Andre, 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 Jimenez, Jimenez-Toscano, Marta, Kanemitsu, Yukihide, Karachun, Aleksei, Karimuddin, Ahmer A., Keller, Deborah S., Kelly, Justin, Kennelly, Rory, Khrykov, Gleb, Kocian, Peter, Koh, Cherry, Kok, Neils, Knight, Katrina A., Knol, Joep, Kontovounisios, Christos, Korner, Hartwig, Krivokapic, Zoran, Kronberger, Irmgard, Kroon, Hidde Maarten, Kryzauskas, Marius, Kural, Said, Kusters, Miranda, Lakkis, Zaher, Lankov, Timur, Larson, David, Lázár, György, Lee, Kai-Yin, Lee, Suk Hwan, Lefèvre, Jeremie H., Lepisto, Anna, Lieu, Christopher, Loi, Lynette, Lynch, Craig, Maillou-Martinaud, Helene, Maroli, Annalisa, Martin, Sean, Martling, Anna, Matzel, Klaus E., Mayol, Julio, McDermott, Frank, Meurette, Guillaume, Millan, Monica, Mitteregger, Martin, Moiseenko, Andrei, Monson, John Rt., Morarasu, Stefan, Moritani, Konosuke, Möslein, Gabriela, Munini, Martino, Nahas, Caio, Nahas, Sergio, Negoi, Ionut, Novikova, Anastasia, Ocares, Misael, Okabayashi, Koji, Olkina, Alexandra, Oñate-Ocaña, Luis, Otero, Jaime, Ozen, Cihan, Pace, Ugo, Julião, Guilherme Pagin S. o, Panaiotti, Lidiia, Panis, Yves, Papamichael, Demetris, Patel, Swati, Uriburu, Juan Carlos Patrón, Peng, Sze-Lin, Pera, Miguel, Perez, Rodrigo O., Petrov, Alexei, Pfeffer, Frank, Phang, Terry P., Poskus, Tomas, Pringle, Heather, Proud, David, Raguz, Ivana, Rama, Nuno, Rasheed, Shahnawaz, Raval, Manoj J., Rega, Daniela, Reissfelder, Christoph, Meneses, Juan Carlos Reyes, Ris, Frederic, Riss, Stefan, Rodriguez-Zentner, Homero, Roxburgh, Campbell S., Saklani, Avanish, Sammour, Tarik, Saraste, Deborah, Schneider, Martin, Seishima, Ryo, Sekulic, Aleksandar, Seppala, Toni, Sheahan, Kieran, Shlomina, Alexandra, Sigismondo, Guiseppe, Singnomklao, Tongplaew, Siragusa, Leandro, Smart, Neil, Solis-Peña, Alejandro, Spinelli, Antonino, Staiger, Roxane D., Stamos, Michael J., Steele, Scott, Tan, Ker-Kan, Tanis, Pieter J., Tekkis, Paris, Teklay, Biniam, Tengku, Sabrina, Tsarkov, Petr, Turina, Matthias, Ulrich, Alexis, Vailati, Bruna B., van Harten, Meike, Verhoef, Cornelis, Warrier, Satish, Wexner, Steven, de Wilt, Hans, Weinberg, Benjamin A., Wells, Cameron, Wolthuis, Albert, Xynos, Evangelos, You, Nancy, Zakharenko, Alexander, Zeballos, Justino, Zhou, Jonathan, Winter, Des C., CCA - Cancer Treatment and Quality of Life, Surgery, CCA - Cancer biology and immunology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Radiology and nuclear medicine, and CCA - Cancer Treatment and quality of life

Subjects
Proto-Oncogene Proteins B-raf, Microsatellite Repeats/genetics, Colonic Neoplasms/genetics, Prognosis, Proto-Oncogene Proteins p21(ras), Proto-Oncogene Proteins p21(ras)/genetics, SDG 3 - Good Health and Well-being, Colonic Neoplasms, Mutation, Proto-Oncogene Proteins B-raf/genetics, Humans, Microsatellite Instability, Surgery, 03.02. Klinikai orvostan, Colorectal Neoplasms, Microsatellite Repeats
Abstract

Background The 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. Methods Anonymized 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. Results A 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). Conclusion Patients 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
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2. 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

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