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. 2020 Aug 9;12(8):2225.
doi: 10.3390/cancers12082225.

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

María Dolores Picó  1 , Ana Beatriz Sánchez-Heras  2 , Adela Castillejo  3 , Mar Giner-Calabuig  4 , Miren Alustiza  4 , Ariadna Sánchez  5 , Leticia Moreira  5 , María Pellise  5 , Antoni Castells  5 , Gemma Llort  6 , Carmen Yagüe  6 , Teresa Ramon Y Cajal  7 , Alexandra Gisbert-Beamud  7 , Joaquin Cubiella  8 , Laura Rivas  8 , Maite Herraiz  9 , Catalina Garau  10 , Inmaculada Salces  11 , Marta Carrillo-Palau  12 , Luis Bujanda  13 , Adriá López-Fernández  14 , Cristina Alvarez-Urturi  15 , María Jesús López  16 , Cristina Alenda  17 , Pedro Zapater  18 , Francisco Javier Lacueva  19 , Francesc Balaguer  5 , Jose-Luis Soto  3 , Óscar Murcia  4 , Rodrigo Jover  4
Affiliations

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

María Dolores Picó et al. Cancers (Basel). .

Abstract

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.

Keywords: colorectal cancer; genetic; risk; surveillance.

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Conflict of interest statement

The authors declare that no competing interests exist.

Figures

Figure 1
Figure 1
Flow diagram of patients and FDR included. FDR, first-degree relatives; LS, Lynch syndrome; LLS, Lynch-like syndrome; CRC, colorectal cancer.
Figure 2
Figure 2
Examples of pedigrees of Lynch syndrome (A) and Lynch-like syndrome (B) families. LS, Lynch syndrome; Dx, diagnosis, Y, years.
Figure 3
Figure 3
Kaplan–Meier curve showing the risk incidence of CRC and other LS-associated tumors during follow-up in the FDRs of patients with LS and LLS. Log Rank, p = 0.000.
See this image and copyright information in PMC

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