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Risk of Cancer in Family Members of Patients with Lynch-Like Syndrome

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Servicio de Medicina Digestiva, Hospital General Universitario de Elche, Elche, 03203 Alicante, Spain
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Servicio de Oncología Médica, Hospital General Universitario de Elche, Elche, 03203 Alicante, Spain
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Unidad de Genética Molecular, Hospital General Universitario de Elche, 03203 Alicante, Spain
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Servicio de Medicina Digestiva, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria ISABIAL, 03010 Alicante, Spain
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Servicio de Medicina Digestiva, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd. University of Barcelona, 08036 Barcelona, Spain
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Servicio de Oncología Médica, Hospital Universitari Parc Taulí, Sabadell, Consorci Sanitari de Terrassa, Terrassa, 08208 Barcelona, Spain
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Servicio de Medicina Digestiva, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
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Servicio de Medicina Digestiva, Complexo Hospitalario Universitario de Ourense, Instituto de Investigación Sanitaria Galicia Sur, CIBERehd, 32005 Ourense, Spain
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Servicio de Medicina Digestiva, Clínica Universidad de Navarra, 31008 Navarra, Spain
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Servicio de Medicina Digestiva, Hospital de Son Llàtzer, 07198 Palma de Mallorca, Spain
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Servicio de Medicina Digestiva, Hospital 12 de Octubre, 28041 Madrid, Spain
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Servicio de Medicina Digestiva, Hospital Universitario de Canarias, 38320 Tenerife, Spain
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Servicio de Medicina Digestiva, Hospital Donostia/Instituto Biodonostia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad del País Vasco (UPV/EHU), 20014 San Sebastián, Spain
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Unidad de Alto Riesgo y Prevención del Cáncer, Hospital Universitario Vall d’Hebron, 08035 Barcelona, Spain
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Servicio de Medicina Digestiva, Hospital del Mar, 08003 Barcelona, Spain
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Servicio de Medicina Digestiva, Hospital Universitario Marqués de Valdecilla, 39008 Santandercity, Spain
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Servicio de Anatomía Patológica, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria ISABIAL, 03010 Alicante, Spain
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Servicio de Farmacología Clínica, Hospital General Universitario de Alicante, ISABIAL, CIBERehd, IDiBE, UMH, 03010 Alicante, Spain
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Servicio de Cirugía general, Hospital General Universitario de Elche, Elche, 03203 Alicante, Spain
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Authors to whom correspondence should be addressed.
Cancers 2020, 12(8), 2225; https://doi.org/10.3390/cancers12082225
Received: 11 July 2020 / Revised: 31 July 2020 / Accepted: 5 August 2020 / Published: 9 August 2020
(This article belongs to the Section Cancer Epidemiology and Prevention)
Lynch syndrome (LS) is a common cause of hereditary colorectal cancer (CRC). Some CRC patients develop mismatch repair deficiency without germline pathogenic mutation, known as Lynch-like syndrome (LLS). We compared the risk of CRC in first-degree relatives (FDRs) in LLS and LS patients. LLS was diagnosed when tumors showed immunohistochemical loss of MSH2, MSH6, and PMS2; or loss of MLH1 with BRAF wild type; and/or no MLH1 methylation and absence of pathogenic mutation in these genes. CRC and other LS-related neoplasms were followed in patients diagnosed with LS and LLS and among their FDRs. Standardized incidence ratios (SIRs) were calculated for CRC and other neoplasms associated with LS among FDRs of LS and LLS patients. In total, 205 LS (1205 FDRs) and 131 LLS families (698 FDRs) had complete pedigrees. FDRs of patients with LLS had a high incidence of CRC (SIR, 2.08; 95% confidence interval (CI), 1.56–2.71), which was significantly lower than that in FDRs of patients with LS (SIR, 4.25; 95% CI, 3.67–4.90; p < 0.001). The risk of developing other neoplasms associated with LS also increased among FDR of LLS patients (SIR, 2.04; 95% CI, 1.44–2.80) but was lower than that among FDR of patients with LS (SIR, 5.01, 95% CI, 4.26–5.84; p < 0.001). FDRs with LLS have an increased risk of developing CRC as well as LS-related neoplasms, although this risk is lower than that of families with LS. Thus, their management should take into account this increased risk. View Full-Text
Keywords: colorectal cancer; risk; genetic; surveillance colorectal cancer; risk; genetic; surveillance
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MDPI and ACS Style

Picó, M.D.; Sánchez-Heras, A.B.; Castillejo, A.; Giner-Calabuig, M.; Alustiza, M.; Sánchez, A.; Moreira, L.; Pellise, M.; Castells, A.; Llort, G.; Yagüe, C.; Ramon y Cajal, T.; Gisbert-Beamud, A.; Cubiella, J.; Rivas, L.; Herraiz, M.; Garau, C.; Salces, I.; Carrillo-Palau, M.; Bujanda, L.; López-Fernández, A.; Alvarez-Urturi, C.; López, M.J.; Alenda, C.; Zapater, P.; Lacueva, F.J.; Balaguer, F.; Soto, J.-L.; Murcia, Ó.; Jover, R. Risk of Cancer in Family Members of Patients with Lynch-Like Syndrome. Cancers 2020, 12, 2225. https://doi.org/10.3390/cancers12082225

AMA Style

Picó MD, Sánchez-Heras AB, Castillejo A, Giner-Calabuig M, Alustiza M, Sánchez A, Moreira L, Pellise M, Castells A, Llort G, Yagüe C, Ramon y Cajal T, Gisbert-Beamud A, Cubiella J, Rivas L, Herraiz M, Garau C, Salces I, Carrillo-Palau M, Bujanda L, López-Fernández A, Alvarez-Urturi C, López MJ, Alenda C, Zapater P, Lacueva FJ, Balaguer F, Soto J-L, Murcia Ó, Jover R. Risk of Cancer in Family Members of Patients with Lynch-Like Syndrome. Cancers. 2020; 12(8):2225. https://doi.org/10.3390/cancers12082225

Chicago/Turabian Style

Picó, María Dolores, Ana Beatriz Sánchez-Heras, Adela Castillejo, Mar Giner-Calabuig, Miren Alustiza, Ariadna Sánchez, Leticia Moreira, María Pellise, Antoni Castells, Gemma Llort, Carmen Yagüe, Teresa Ramon y Cajal, Alexandra Gisbert-Beamud, Joaquin Cubiella, Laura Rivas, Maite Herraiz, Catalina Garau, Inmaculada Salces, Marta Carrillo-Palau, Luis Bujanda, Adriá López-Fernández, Cristina Alvarez-Urturi, María Jesús López, Cristina Alenda, Pedro Zapater, Francisco Javier Lacueva, Francesc Balaguer, Jose-Luis Soto, Óscar Murcia, and Rodrigo Jover. 2020. "Risk of Cancer in Family Members of Patients with Lynch-Like Syndrome" Cancers 12, no. 8: 2225. https://doi.org/10.3390/cancers12082225

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