Risk of cancer in individuals with Lynch-like syndrome and their families: a systematic review

doi:10.1007/s00432-022-04397-0

. 2023 Jan;149(1):25-46.

doi: 10.1007/s00432-022-04397-0. Epub 2022 Oct 17.

Risk of cancer in individuals with Lynch-like syndrome and their families: a systematic review

Pandu P Nugroho^#^{1

2}, Siti Alyaa S Ghozali^#^{1

2}, Daniel D Buchanan^{3

4

5}, Mia I Pisano⁶, Jeanette C Reece⁷

Affiliations

¹ Faculty of Medicine, Universitas Indonesia, Depok, West Java, Indonesia.
² Melbourne Medical School, The University of Melbourne, Parkville, VIC, Australia.
³ Colorectal Oncogenomics Group, Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Parkville, VIC, Australia.
⁴ University of Melbourne Centre for Cancer Research, Parkville, VIC, Australia.
⁵ Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, VIC, Australia.
⁶ Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia.
⁷ Neuroepidemiology Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Level 3 207 Bouverie Street, Parkville, VIC, 3010, Australia. jreece@unimelb.edu.au.

^# Contributed equally.

PMID: 36251064
PMCID: PMC9889410
DOI: 10.1007/s00432-022-04397-0

Risk of cancer in individuals with Lynch-like syndrome and their families: a systematic review

Pandu P Nugroho et al. J Cancer Res Clin Oncol. 2023 Jan.

. 2023 Jan;149(1):25-46.

doi: 10.1007/s00432-022-04397-0. Epub 2022 Oct 17.

Authors

Pandu P Nugroho^#^{1

2}, Siti Alyaa S Ghozali^#^{1

2}, Daniel D Buchanan^{3

4

5}, Mia I Pisano⁶, Jeanette C Reece⁷

Affiliations

¹ Faculty of Medicine, Universitas Indonesia, Depok, West Java, Indonesia.
² Melbourne Medical School, The University of Melbourne, Parkville, VIC, Australia.
³ Colorectal Oncogenomics Group, Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Parkville, VIC, Australia.
⁴ University of Melbourne Centre for Cancer Research, Parkville, VIC, Australia.
⁵ Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, VIC, Australia.
⁶ Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia.
⁷ Neuroepidemiology Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Level 3 207 Bouverie Street, Parkville, VIC, 3010, Australia. jreece@unimelb.edu.au.

^# Contributed equally.

PMID: 36251064
PMCID: PMC9889410
DOI: 10.1007/s00432-022-04397-0

Abstract

Background: Lynch-like syndrome (LLS) tumors have similar clinicopathological features to Lynch syndrome (LS) tumors but have no identifiable pathogenic germline mismatch repair gene variant. However, cancer risks in LLS patients and first-degree relatives (FDRs) are not well defined.

Methods: To clarify LLS-associated cancer risks, a systematic review of all studies examining all cancer risks in LLS was performed. Searching of Medline, Embase, Pubmed, Cochrane and CINAHL databases and reference/citation checking identified relevant studies published between January 1, 1980 and February 11, 2021. Joanna Briggs Institute Appraisal Tools assessed the risk of bias.

Results: Six studies (five cohort/one cross-sectional) were eligible for study inclusion. One study found no difference in colorectal cancer (CRC) incidence between LLS and LS patients or CRC risks at aged 70 years. Three studies found CRC incidence in LLS FDRs was higher than the general population but lower than LS FDRs. Two studies showed no difference in CRC diagnosis age between LLS patients and LS patients. Endometrial cancer risks in LLS patients were higher than the general population but lower than LS patients.

Conclusion: Evidence of elevated CRC risks in LLS patients and FDRs supports increased colonoscopy surveillance strategies for LLS patients and FDRs in line with current recommendations for LS. Due to heterogeneity amongst LLS populations, extended intervals between screening may be advised for low-risk families. Studies to resolve the molecular characterization and definition of LLS are needed to clarify cancer risks associated with LLS which in turn may individualize surveillance strategies for LLS patients and families.

Keywords: Colorectal cancer; Extra-colonic cancer; Lynch syndrome; Lynch-like syndrome; Standard incidence ratio.

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Conflict of interest statement

The authors declare no competing interests.

The authors declare no conflict of interest.

Figures

**Fig. 1**
PRISMA flow diagram of inclusion of studies

See this image and copyright information in PMC

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References

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[1] Alvarez-Lafuente R, De Las Heras V, Bartolome M, Picazo JJ, Arroyo R. Beta-interferon treatment reduces human herpesvirus-6 viral load in multiple sclerosis relapses but not in remission. Eur Neurol. 2004;52(2):87–91. doi: 10.1159/000079936. - DOI - PubMed

[2] Alvarez-Lafuente R, De Las Heras V, Bartolome M, Picazo JJ, Arroyo R. Beta-interferon treatment reduces human herpesvirus-6 viral load in multiple sclerosis relapses but not in remission. Eur Neurol. 2004;52(2):87–91. doi: 10.1159/000079936. - DOI - PubMed

[3] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 doi: 10.3322/caac.21492. - DOI - PubMed

[4] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 doi: 10.3322/caac.21492. - DOI - PubMed

[5] Buchanan DD, Rosty C, Clendenning M, Spurdle AB, Win AK. Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome) Appl Clin Genet. 2014;7:183–193. doi: 10.2147/TACG.S48625. - DOI - PMC - PubMed

[6] Buchanan DD, Rosty C, Clendenning M, Spurdle AB, Win AK. Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome) Appl Clin Genet. 2014;7:183–193. doi: 10.2147/TACG.S48625. - DOI - PMC - PubMed

[7] Bucksch K, Zachariae S, Aretz S, Buttner R, Holinski-Feder E, Holzapfel S, Huneburg R, Kloor M, von Knebel Doeberitz M, Morak M, Moslein G, Nattermann J, Perne C, Rahner N, Schmiegel W, Schulmann K, Steinke-Lange V, Strassburg CP, Vangala DB, Weitz J, Loeffler M, Engel C, German Consortium for Familial Intestinal, C Cancer risks in Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X: a prospective cohort study. BMC Cancer. 2020;20(1):460. doi: 10.1186/s12885-020-06926-x. - DOI - PMC - PubMed

[8] Bucksch K, Zachariae S, Aretz S, Buttner R, Holinski-Feder E, Holzapfel S, Huneburg R, Kloor M, von Knebel Doeberitz M, Morak M, Moslein G, Nattermann J, Perne C, Rahner N, Schmiegel W, Schulmann K, Steinke-Lange V, Strassburg CP, Vangala DB, Weitz J, Loeffler M, Engel C, German Consortium for Familial Intestinal, C Cancer risks in Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X: a prospective cohort study. BMC Cancer. 2020;20(1):460. doi: 10.1186/s12885-020-06926-x. - DOI - PMC - PubMed

[9] Cancer Genome Atlas N Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487(7407):330–337. doi: 10.1038/nature11252. - DOI - PMC - PubMed

[10] Cancer Genome Atlas N Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487(7407):330–337. doi: 10.1038/nature11252. - DOI - PMC - PubMed

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Risk of cancer in individuals with Lynch-like syndrome and their families: a systematic review

Affiliations

Risk of cancer in individuals with Lynch-like syndrome and their families: a systematic review

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Abstract

Conflict of interest statement

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Abstract

Conflict of interest statement

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