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

Win, Aung Ko; Dowty, James G.; Reece, Jeanette C.; Lee, Grant; Templeton, Allyson; Plazzer, John‐Paul; Buchanan, Daniel D.; Akagi, Kiwamu; Aksoy, Seçil Ak; Alonso, Ángel; Álvarez, Karin; Amor, David J.; Ankathil, Ravindran; Aretz, Stefan; Arnold, Julie; Aronson, Melyssa; Austin, Rachel; Backman, Ann-Sofie; Broeke, Sanne W. Bajwa–ten; Barca-Tierno, Verónica; Barwell, Julian; Bernstein, Inge; Berthet, Pascaline; Betz, Beate; Bignon, Yves‐Jean; Boisjoli, Talya; Bonadona, Valérie; Briollais, Laurent; Brunet, Joan; Bucksch, Karolin; Bruno, Benedetto; Buettner, Reinhard; Burn, John; Caldés, Trinidad; Capellà, Gabriel; Caron, Olivier; Casey, Graham; Chew, Min Hoe; Choi, Yunhee; Church, James M.; Clendenning, Mark; Colas, Chrystelle; Cops, Elisa J.; Coupier, Isabelle; Cruz‐Correa, Marcia; Chapelle, Albert de la; Wind, Niels de; Dębniak, Tadeusz; Valle, Adriana Della; Delnatte, Capuccine; Dhooge, Marion; Dominguez‐Valentin, Mev; Drouet, Youenn; Duijkers, Floor A.M.; Engel, Christoph; Esperón, Patricia; Evans, D. Gareth; Vargas, Aı́da Falcón de; Figueiredo, Jane C.; Foulkes, William D.; Fourme, Emmanuelle; Frébourg, Thierry; Gallinger, Steven; Garré, Pilar; Genuardi, Maurizio; Gerdes, Anne-Marie; Gima, Lauren M.; Giraud, Sophie; Goodwin, Annabel; Görgens, Heike; Green, Kate; Guillem, José G.; Guillén‐Ponce, Carmen; Guimbaud, Roselyne; Guindalini, Rodrigo Santa Cruz; Half, Elizabeth E.; Hall, Michael J.; Hampel, Heather; Hansen, Thomas van Overeem; Heinimann, Karl; Hes, Frederik J.; Hill, James A.; Ho, Judy; Holinski‐Feder, Elke; Hoogerbrugge, Nicoline; Hüneburg, Robert; Huntley, Vanessa; James, P.; Jensen, Uffe Birk; John, Thomas; Juhari, Wan Khairunnisa Wan; Kalady, Matthew F.; Kastrinos, Fay; Kloor, Matthias; Kohonen‐Corish, Maija; Krogh, Lotte Nylandsted; Kupfer, Sonia S.; Ladabaum, Uri; Lagerstedt‐Robinson, Kristina; Lalloo, Fiona; Lasset, Christine; Latchford, Andrew; Laurent–Puig, Pierre; Lautrup, Charlotte Kvist; Leggett, Barbara A.; Lejeune, Sophie; LeMarchand, Loïc; Ligtenberg, Marjolijn J. L.; Lindor, Noralane M.; Loeffler, Markus; Longy, Michel; López, Francisco; Lowery, Jan T.; Lubiński, Jan; Lucassen, Anneke; 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 W.; Newcomb, Polly A.; Ngeow, Joanne; Nichols, Cassandra; Nielsen, Maartje; Nixon, Dawn M.; Noguès, Catherine; Okkels, Henrik; Olschwang, Sylviane; Pachter, Nicholas; Pai, Rish K.; Palmero, Edenir Inêz; Pande, Mala; Parry, Susan; Patel, Swati; Pearlman, Rachel; Perne, Claudia; Pineda, Marta; Poplawski, Nicola; Pylvänäinen, Kirsi; Qiu, Jay; Rahner, Nils; Ramesar, Raj; Rasmussen, Lene Juel; Redler, Silke; Reis, Rui Manuel; Ricciardiello, Luigi; Rogoża-Janiszewska, Emilia; Rosty, Christophe; Samadder, N. Jewel; Sampson, Julian R.; Schackert, Hans K.; Schmiegel, Wolff; Schulmann, Karsten; Schuster, Hélène; Scott, Rodney J.; Senter, Leigha; Seppälä, Toni T.; Shtoyerman, Rakefet; Sijmons, Rolf H.; Snyder, Carrie; Solomon, Ilana; Soto, José Luís; Southey, Melissa C.; Spigelman, Allan D.; 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, S. N.; Tomita, Naohiro; Tucker, Katherine; Tunca, Berrin; Turchetti, Daniela; Uhrhammer, Nancy; Utsunomiya, Joji; Vaccaro, Carlos; Duijnhoven, Fränzel J.B. van; Wanzeele, Meghan J. van; Vangala, Deepak B.; Vasen, Hans F. A.; Doeberitz, Magnus von Knebel; Salomé, Jenny von; Wadt, Karin; 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 Nizam; Hopper, John L.; Haile, Robert W.; Macrae, Finlay; Möslein, Gabriela; Jenkins, Mark A.

doi:10.1016/s1470-2045(21)00189-3

Cited by 70 publications

(47 citation statements)

References 27 publications

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“…Like the IGCLC, we would not recommend prophylactic total gastrectomy or bilateral mastectomy in the absence of significant family history. A similar situation has recently been reported in Lynch syndrome where very important phenotypic differences are being unveiled even within the same gene when comparing different families 20. We hope this study fosters further research and helps the scientific community appreciate even more the complexity of CDH1 germline mutations and the associated phenotypes.…”

Section: Discussionsupporting

confidence: 75%

Simplified and more sensitive criteria for identifying individuals with pathogenicCDH1variants

et al. 2022

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BackgroundHereditary diffuse gastric cancer (HDGC) is an autosomal-dominant syndrome most often caused by pathogenic variants in CDH1. The International Gastric Cancer Linkage Consortium (IGCLC) recently updated its criteria for genetic testing. The purpose of this study was to estimate the sensitivity of IGCLC’s 2020 criteria for identifying carriers of CDH1 pathogenic variants and to formulate a new set of criteria that is simpler and more sensitive.MethodsMedical histories of 112 CDH1 mutation carriers, identified predominantly by multigene panel testing, and their 649 family members were reviewed. The percentage of subjects fulfilling the IGCLC 2015 and 2020 criteria was calculated, once without making any assumptions about unavailable pathology, and once assuming gastric cancer to be diffuse when pathology was unavailable. For comparison, we calculated the percentage of subjects who fulfilled our proposed criteria.ResultsWhen making no assumptions about missing pathology, a small (19%) and equal percentage of CDH1 mutation carriers fulfilled the IGCLC 2015 and 2020 criteria. When assuming unspecified gastric cancer to be diffuse, 45 out of 112 (40%) subjects met the 2015 criteria and 53 out of 112 (47%) met the 2020 criteria. Eighty-seven per cent (97/112) fulfilled our proposed criteria.ConclusionIn consecutive cases, mostly unselected for clinical criteria of HDGC, the IGCLC 2020 criteria are, at best, marginally more sensitive than previous iterations, but they are also more cumbersome. Unavailable cancer pathology reports are a real-world obstacle to their proper application. Our proposed Yale criteria both address this issue and offer significantly greater sensitivity than the IGCLC 2020 criteria.

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Section: Discussionsupporting

confidence: 75%

Simplified and more sensitive criteria for identifying individuals with pathogenicCDH1variants

et al. 2022

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“…While the reasons for this observation are not completely understood, it represents an important argument for the discussion of extended surgery [19]. Increasing evidence suggests that cancer risk is not only influenced by the path_MMR gene but also by gender, genetic modifiers, obesity, and lifestyle factors such as physical activity, smoking, alcohol consumption, diet, and even continent of residence [20,21]. Therefore, an individual's risk assessment needs to consider the patient's age, comorbidities, and genotype, as well as expected functional outcome and priorities.…”

Section: Defining the Risk Of Metachronous Cancer In Lynch Syndrome P...mentioning

confidence: 99%

Risk of Metachronous Colorectal Cancer in Lynch Syndrome: Who Needs an Extended Resection?

Doerner

2022

Surgeries

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Lynch syndrome (LS) is the most common genetic condition associated with early-onset colorectal cancer. It is inherited in an autosomal dominant fashion. The increased cancer risk is due to a germline mutation in one of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) or the EPCAM gene. This leads to a deficient DNA mismatch repair mechanism, resulting in the accumulation of nucleotide changes and microsatellite instability, providing phenotypical evidence that MMR is not functioning normally. LS is associated with a high risk of early-onset colorectal cancer and recurrence. Thus, when undergoing surgery for primary colorectal cancer, extended resection should be discussed with the patient. This review provides an overview of current surgical risk-reducing strategies in LS-associated colorectal cancer. Surgical treatment for LS carriers with colorectal cancer needs to be highly individualized, based on patient and disease characteristics. Strategies are presented to guide decision making in pathologic MMR gene mutation carriers undergoing surgery for colorectal cancer.

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“…A number of different environmental and genetic factors play a major role in the pathogenesis of CRC. Hereditary CRC syndromes including Lynch syndrome (hereditary nonpolyposis colorectal cancer), familial adenomatous polyposis (FAP), and multiple associated polyposis (MAP) 3 , 4 can predispose an individual to increased risk of CRC. Chronic inflammatory stimulation, schistosomiasis infection, diet and other environmental factors can also promote the occurrence of CRC.…”

Section: Introductionmentioning

confidence: 99%

Fusobacterium nucleatum and Colorectal Cancer

Li¹,

Shen²,

Xu³

2022

IDR

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Fusobacterium nucleatum ( F.n ) is an oral anaerobic gram-negative bacillus that can colonize into the colon tissues through bloodstream infection. F.n have been found to be involved in both the occurrence and metastasis of colorectal cancer (CRC) through regulating immune response, virulence factor, oncogenic microRNAs, intestinal metabolites, DNA damage and other mechanisms. Therefore, F.n can be as an important pathogenic risk factor and a possible biomarker of CRC. Based on this, we have summarized the potential relationship between F.n and CRC to provide reference for the targeted therapy of CRC.

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

Cited by 70 publications

References 27 publications

Simplified and more sensitive criteria for identifying individuals with pathogenicCDH1variants

Simplified and more sensitive criteria for identifying individuals with pathogenicCDH1variants

Risk of Metachronous Colorectal Cancer in Lynch Syndrome: Who Needs an Extended Resection?

Fusobacterium nucleatum and Colorectal Cancer

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