Comparison of Molecular, Clinicopathological, and Pedigree Differences Between Lynch-Like and Lynch Syndromes
In this study, we compared the molecular, clinical, and pathological characteristics, as well as pedigrees, between patients with Lynch-like syndrome (LLS) and confirmed Lynch syndrome (LS) to develop appropriate management strategies for patients with LLS and their affected family members. Between...
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| Format: | Article |
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2020.00991/full |
| _version_ | 1828463668476510208 |
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| author | Yun Xu Yun Xu Zonghao Huang Cong Li Cong Li Congcong Zhu Yuqin Zhang Tian’an Guo Fangqi Liu Ye Xu Ye Xu |
| author_facet | Yun Xu Yun Xu Zonghao Huang Cong Li Cong Li Congcong Zhu Yuqin Zhang Tian’an Guo Fangqi Liu Ye Xu Ye Xu |
| author_sort | Yun Xu |
| collection | DOAJ |
| description | In this study, we compared the molecular, clinical, and pathological characteristics, as well as pedigrees, between patients with Lynch-like syndrome (LLS) and confirmed Lynch syndrome (LS) to develop appropriate management strategies for patients with LLS and their affected family members. Between June 2008 and September 2018, 81 patients with LLS and 47 patients with LS who developed colorectal cancer (CRC) were enrolled in this study. Multigene panel testing included 139 genes and was performed for all patients. The variants identified in each group were described, and clinicopathological characteristics and pedigrees were compared between the two groups. In the LLS group, a total of 52 variants were detected in 44 (54.3%) patients. Among the 52 variants, 17 were variants of unknown significance in mismatch repair genes, and the other most frequently mutated genes were MUYTH, POLE, BRCA2, and GJB2. The proportion of early-onset patients was significantly higher among the LS probands than among the LLS probands (74.5 and 53.1%, respectively; χ2 = 5.712, P = 0.017). On the other hand, the proportion of primary CRC developed in the rectum was higher in the LLS group than in the LS group (25.9 and 10.6%, respectively; χ2 = 2.358, P = 0.046). There were no significant differences in the occurrence of metachronous CRC (P = 0.632) and extra-colorectal cancer (extra-CRC) (P = 0.145) between the two groups. However, analysis of pedigrees showed that more patients developed CRC in the LS families (P = 0.013), whereas more patients with extra-CRC were observed in the LLS families (P = 0.045). A higher prevalence of male patients was observed in the LLS families (P = 0.036). In conclusion, LLS should be classified as a mixed entity, containing cases of LS, other hereditary cancer syndromes, and sporadic CRC. The high risks of CRC and extra-CRCs, which were found in this study, suggest tailored management policy and surveillance should be formulated based on individual and family risk. The surveillance regimen can be based on the presence of confirmed pathogenic/likely pathogenic germline variant(s) and family history. |
| first_indexed | 2024-12-11T02:57:05Z |
| format | Article |
| id | doaj.art-9595fbab61694b53aa20fd02be96a46b |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-11T02:57:05Z |
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| spelling | doaj.art-9595fbab61694b53aa20fd02be96a46b2022-12-22T01:23:07ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-08-011110.3389/fgene.2020.00991564813Comparison of Molecular, Clinicopathological, and Pedigree Differences Between Lynch-Like and Lynch SyndromesYun Xu0Yun Xu1Zonghao Huang2Cong Li3Cong Li4Congcong Zhu5Yuqin Zhang6Tian’an Guo7Fangqi Liu8Ye Xu9Ye Xu10Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaHospital Information Centre, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaIn this study, we compared the molecular, clinical, and pathological characteristics, as well as pedigrees, between patients with Lynch-like syndrome (LLS) and confirmed Lynch syndrome (LS) to develop appropriate management strategies for patients with LLS and their affected family members. Between June 2008 and September 2018, 81 patients with LLS and 47 patients with LS who developed colorectal cancer (CRC) were enrolled in this study. Multigene panel testing included 139 genes and was performed for all patients. The variants identified in each group were described, and clinicopathological characteristics and pedigrees were compared between the two groups. In the LLS group, a total of 52 variants were detected in 44 (54.3%) patients. Among the 52 variants, 17 were variants of unknown significance in mismatch repair genes, and the other most frequently mutated genes were MUYTH, POLE, BRCA2, and GJB2. The proportion of early-onset patients was significantly higher among the LS probands than among the LLS probands (74.5 and 53.1%, respectively; χ2 = 5.712, P = 0.017). On the other hand, the proportion of primary CRC developed in the rectum was higher in the LLS group than in the LS group (25.9 and 10.6%, respectively; χ2 = 2.358, P = 0.046). There were no significant differences in the occurrence of metachronous CRC (P = 0.632) and extra-colorectal cancer (extra-CRC) (P = 0.145) between the two groups. However, analysis of pedigrees showed that more patients developed CRC in the LS families (P = 0.013), whereas more patients with extra-CRC were observed in the LLS families (P = 0.045). A higher prevalence of male patients was observed in the LLS families (P = 0.036). In conclusion, LLS should be classified as a mixed entity, containing cases of LS, other hereditary cancer syndromes, and sporadic CRC. The high risks of CRC and extra-CRCs, which were found in this study, suggest tailored management policy and surveillance should be formulated based on individual and family risk. The surveillance regimen can be based on the presence of confirmed pathogenic/likely pathogenic germline variant(s) and family history.https://www.frontiersin.org/article/10.3389/fgene.2020.00991/fullcolorectal cancerLynch syndromeLynch-like syndromepedigreeDNA mismatch repair |
| spellingShingle | Yun Xu Yun Xu Zonghao Huang Cong Li Cong Li Congcong Zhu Yuqin Zhang Tian’an Guo Fangqi Liu Ye Xu Ye Xu Comparison of Molecular, Clinicopathological, and Pedigree Differences Between Lynch-Like and Lynch Syndromes Frontiers in Genetics colorectal cancer Lynch syndrome Lynch-like syndrome pedigree DNA mismatch repair |
| title | Comparison of Molecular, Clinicopathological, and Pedigree Differences Between Lynch-Like and Lynch Syndromes |
| title_full | Comparison of Molecular, Clinicopathological, and Pedigree Differences Between Lynch-Like and Lynch Syndromes |
| title_fullStr | Comparison of Molecular, Clinicopathological, and Pedigree Differences Between Lynch-Like and Lynch Syndromes |
| title_full_unstemmed | Comparison of Molecular, Clinicopathological, and Pedigree Differences Between Lynch-Like and Lynch Syndromes |
| title_short | Comparison of Molecular, Clinicopathological, and Pedigree Differences Between Lynch-Like and Lynch Syndromes |
| title_sort | comparison of molecular clinicopathological and pedigree differences between lynch like and lynch syndromes |
| topic | colorectal cancer Lynch syndrome Lynch-like syndrome pedigree DNA mismatch repair |
| url | https://www.frontiersin.org/article/10.3389/fgene.2020.00991/full |
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