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

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 dia...

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Autores principales: Picó, María Dolores, Sánchez-Heras, Ana Beatriz, Castillejo, Adela, Giner-Calabuig, Mar, Alustiza, Miren, Sánchez, Ariadna, Moreira, Leticia, Pellise, María, Castells, Antoni, Llort, Gemma, Yagüe, Carmen, Ramon y Cajal, Teresa, Gisbert-Beamud, Alexandra, Cubiella, Joaquin, Rivas, Laura, Herraiz, Maite, Garau, Catalina, Salces, Inmaculada, Carrillo-Palau, Marta, Bujanda, Luis, López-Fernández, Adriá, Alvarez-Urturi, Cristina, López, María Jesús, Alenda, Cristina, Zapater, Pedro, Lacueva, Francisco Javier, Balaguer, Francesc, Soto, Jose-Luis, Murcia, Óscar, Jover, Rodrigo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466118/
https://www.ncbi.nlm.nih.gov/pubmed/32784934
http://dx.doi.org/10.3390/cancers12082225
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author Picó, María Dolores
Sánchez-Heras, Ana Beatriz
Castillejo, Adela
Giner-Calabuig, Mar
Alustiza, Miren
Sánchez, Ariadna
Moreira, Leticia
Pellise, María
Castells, Antoni
Llort, Gemma
Yagüe, Carmen
Ramon y Cajal, Teresa
Gisbert-Beamud, Alexandra
Cubiella, Joaquin
Rivas, Laura
Herraiz, Maite
Garau, Catalina
Salces, Inmaculada
Carrillo-Palau, Marta
Bujanda, Luis
López-Fernández, Adriá
Alvarez-Urturi, Cristina
López, María Jesús
Alenda, Cristina
Zapater, Pedro
Lacueva, Francisco Javier
Balaguer, Francesc
Soto, Jose-Luis
Murcia, Óscar
Jover, Rodrigo
author_facet Picó, María Dolores
Sánchez-Heras, Ana Beatriz
Castillejo, Adela
Giner-Calabuig, Mar
Alustiza, Miren
Sánchez, Ariadna
Moreira, Leticia
Pellise, María
Castells, Antoni
Llort, Gemma
Yagüe, Carmen
Ramon y Cajal, Teresa
Gisbert-Beamud, Alexandra
Cubiella, Joaquin
Rivas, Laura
Herraiz, Maite
Garau, Catalina
Salces, Inmaculada
Carrillo-Palau, Marta
Bujanda, Luis
López-Fernández, Adriá
Alvarez-Urturi, Cristina
López, María Jesús
Alenda, Cristina
Zapater, Pedro
Lacueva, Francisco Javier
Balaguer, Francesc
Soto, Jose-Luis
Murcia, Óscar
Jover, Rodrigo
author_sort Picó, María Dolores
collection PubMed
description 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.
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spelling pubmed-74661182020-09-14 Risk of Cancer in Family Members of Patients with Lynch-Like Syndrome Picó, María Dolores Sánchez-Heras, Ana Beatriz Castillejo, Adela Giner-Calabuig, Mar Alustiza, Miren Sánchez, Ariadna Moreira, Leticia Pellise, María Castells, Antoni Llort, Gemma Yagüe, Carmen Ramon y Cajal, Teresa Gisbert-Beamud, Alexandra Cubiella, Joaquin Rivas, Laura Herraiz, Maite Garau, Catalina Salces, Inmaculada Carrillo-Palau, Marta Bujanda, Luis López-Fernández, Adriá Alvarez-Urturi, Cristina López, María Jesús Alenda, Cristina Zapater, Pedro Lacueva, Francisco Javier Balaguer, Francesc Soto, Jose-Luis Murcia, Óscar Jover, Rodrigo Cancers (Basel) Article 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. MDPI 2020-08-09 /pmc/articles/PMC7466118/ /pubmed/32784934 http://dx.doi.org/10.3390/cancers12082225 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Picó, María Dolores
Sánchez-Heras, Ana Beatriz
Castillejo, Adela
Giner-Calabuig, Mar
Alustiza, Miren
Sánchez, Ariadna
Moreira, Leticia
Pellise, María
Castells, Antoni
Llort, Gemma
Yagüe, Carmen
Ramon y Cajal, Teresa
Gisbert-Beamud, Alexandra
Cubiella, Joaquin
Rivas, Laura
Herraiz, Maite
Garau, Catalina
Salces, Inmaculada
Carrillo-Palau, Marta
Bujanda, Luis
López-Fernández, Adriá
Alvarez-Urturi, Cristina
López, María Jesús
Alenda, Cristina
Zapater, Pedro
Lacueva, Francisco Javier
Balaguer, Francesc
Soto, Jose-Luis
Murcia, Óscar
Jover, Rodrigo
Risk of Cancer in Family Members of Patients with Lynch-Like Syndrome
title Risk of Cancer in Family Members of Patients with Lynch-Like Syndrome
title_full Risk of Cancer in Family Members of Patients with Lynch-Like Syndrome
title_fullStr Risk of Cancer in Family Members of Patients with Lynch-Like Syndrome
title_full_unstemmed Risk of Cancer in Family Members of Patients with Lynch-Like Syndrome
title_short Risk of Cancer in Family Members of Patients with Lynch-Like Syndrome
title_sort risk of cancer in family members of patients with lynch-like syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466118/
https://www.ncbi.nlm.nih.gov/pubmed/32784934
http://dx.doi.org/10.3390/cancers12082225
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