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. 2019 Apr;10(2):259-266.
doi: 10.1007/s12687-018-0385-1. Epub 2018 Sep 24.

Hereditary colorectal cancer diagnostics in southern Sweden: retrospective evaluation and future considerations with emphasis on Lynch syndrome

Isabelle Henriksson  1 , Karin Henriksson  1 , Hans Ehrencrona  1   2 , Samuel Gebre-Medhin  3   4   5
Affiliations

Hereditary colorectal cancer diagnostics in southern Sweden: retrospective evaluation and future considerations with emphasis on Lynch syndrome

Isabelle Henriksson et al. J Community Genet. 2019 Apr.

Abstract

Overlapping phenotypes between different hereditary colorectal cancer (CRC) syndromes together with a growing demand for cancer genetic testing and improved sequencing technology call for adjusted patient selection and adapted diagnostic routines. Here we present a retrospective evaluation of family history of cancer, laboratory diagnostic procedure, and outcome for 372 patients tested for Lynch syndrome (LS), i.e., the single most common hereditary cause of CRC. Based on number of affected family members and age at cancer diagnosis in families with genetically confirmed LS, we developed local patient selection criteria for a simplified one-step gene panel mutation screening strategy targeting also less common Mendelian CRC syndromes. Pros and cons of this strategy are discussed.

Keywords: Cancer; Colorectal; Gene panel; Hereditary; Screening.

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Conflict of interest statement

Conflict of interest

The authors declare no conflicts of interest.

Ethical approval

This study constitutes a retrospective evaluation of clinical data and was part of a quality assessment project at the Department of Clinical Genetics in Lund. Informed written consent for cancer genetic investigation was collected from each proband as part of the clinical routine.

Figures

Fig. 1
Fig. 1
Number of LS-associated tumors in clusters of first-degree relatives (CFDR), lowest age at diagnosis (LAD), and laboratory outcome for patients subjected to MMR gene mutation screening. Each data point represents a CFDR. VUS: variant of uncertain significance. Proposed cutoff for direct gene panel mutation screening is indicated (dashed line)
Fig. 2
Fig. 2
Number of LS-associated tumors in clusters of first-degree relatives (CFDR) and lowest age at diagnosis (LAD) for entire cohort. Each data point represents a CFDR. Proposed cutoff for direct gene panel mutation screening is indicated (dashed line)
Fig. 3
Fig. 3
Number of LS-associated tumors in clusters of first-degree relatives (CFDR) and lowest age at diagnosis (LAD), and outcome in patients subjected to MMR functional analysis. Each data point represents a CFDR. Outcome of MMR functional analysis (n = 368); proposed cutoff for direct gene panel testing is indicated (dashed line) (a). Relative frequency bar graphs and notched box plots visualizing the relationship between MMR functional status and number of tumors in CFDR (b) or LAD (c), respectively
See this image and copyright information in PMC

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References

    1. Aaltonen LA, Peltomäki P, Leach FS, Sistonen P, Pylkkänen L, Mecklin JP, Järvinen H, Powell SM, Jen J, Hamilton SR, et al. Clues to the pathogenesis of familial colorectal cancer. Science. 1993;260(5109):812–816. doi: 10.1126/science.8484121. - DOI - PubMed
    1. Aretz S. The differential diagnosis and surveillance of hereditary gastrointestinal polyposis syndromes. Dtsch Arztebl Int. 2010;107(10):163–173. - PMC - PubMed
    1. Baglietto L, Lindor NM, Dowty JG, White DM, Wagner A, Gomez Garcia EB, Vriends AH, G. Dutch Lynch Syndrome Study. Cartwright NR, Barnetson RA, Farrington SM, Tenesa A, Hampel H, Buchanan D, Arnold S, Young J, Walsh MD, Jass J, Macrae F, Antill Y, Winship IM, Giles GG, Goldblatt J, Parry S, Suthers G, Leggett B, Butz M, Aronson M, Poynter JN, Baron JA, Le Marchand L, Haile R, Gallinger S, Hopper JL, Potter J, de la Chapelle A, Vasen HF, Dunlop MG, Thibodeau SN, Jenkins MA. Risks of lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst. 2010;102(3):193–201. doi: 10.1093/jnci/djp473. - DOI - PMC - PubMed
    1. Bapat B, Lindor NM, Baron J, Siegmund K, Li L, Zheng Y, Haile R, Gallinger S, Jass JR, Young JP, Cotterchio M, Jenkins M, Grove J, Casey G, Thibodeau SN, Bishop DT, Hopper JL, Ahnen D, Newcomb PA, Le Marchand L, Potter JD, Seminara D, R. Colon Cancer Family The association of tumor microsatellite instability phenotype with family history of colorectal cancer. Cancer Epidemiol Biomark Prev. 2009;18(3):967–975. doi: 10.1158/1055-9965.EPI-08-0878. - DOI - PMC - PubMed
    1. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S. A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998;58(22):5248–5257. - PubMed

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