Lynch syndrome: influence of additional susceptibility variants on cancer risk
Roseline Vibert
(1, 2)
,
Jasmine Hasnaoui
(1, 2)
,
Alexandre Perrier
(1, 2)
,
Alexandra Lefebvre
(3, 4, 5)
,
Chrystelle Colas
(6, 7)
,
Marion Dhooge
(8)
,
Noémie Basset
(1, 2)
,
Albain Chansavang
(8, 9)
,
Camille Desseignes
(1, 2)
,
Alex Duval
(4, 5)
,
Solenne Farelly
(8)
,
Nadim Hamzaoui
(8, 9)
,
Pierre Laurent-Puig
(10, 11)
,
Julie Metras
(12)
,
Diane Moliere
(10, 11)
,
Martine Muleris
(1, 2, 4, 5)
,
Jeanne Netter
(10, 11)
,
Mehdi Touat
(2, 13, 5)
,
Franck Bielle
(2)
,
Karim Labreche
(14)
,
Romain Nicolle
(1, 2)
,
Géraldine Perkins
(10)
,
Mathilde Warcoin
(6)
,
Florence Coulet
(1, 2, 4, 5)
,
Patrick Benusiglio
(1, 2, 4, 5, 12)
1
IUC -
Institut Universitaire de Cancérologie [Sorbonne Université]
2 CHU Pitié-Salpêtrière [AP-HP]
3 LPSM (UMR_8001) - Laboratoire de Probabilités, Statistique et Modélisation
4 CRSA - Centre de Recherche Saint-Antoine
5 SiRIC CURAMUS - Site de recherche intégrée en cancérologie
6 Institut Curie [Paris]
7 U830 - Unité de génétique et biologie des cancers
8 Hôpital Cochin [AP-HP]
9 IC UM3 (UMR 8104 / U1016) - Institut Cochin
10 SIRIC CARPEM - Cancer Research and Personalized Medicine - CARPEM [Paris]
11 UPCité - Université Paris Cité
12 CHU Saint-Antoine [AP-HP]
13 ICM - Institut du Cerveau = Paris Brain Institute
14 PASS - Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé
2 CHU Pitié-Salpêtrière [AP-HP]
3 LPSM (UMR_8001) - Laboratoire de Probabilités, Statistique et Modélisation
4 CRSA - Centre de Recherche Saint-Antoine
5 SiRIC CURAMUS - Site de recherche intégrée en cancérologie
6 Institut Curie [Paris]
7 U830 - Unité de génétique et biologie des cancers
8 Hôpital Cochin [AP-HP]
9 IC UM3 (UMR 8104 / U1016) - Institut Cochin
10 SIRIC CARPEM - Cancer Research and Personalized Medicine - CARPEM [Paris]
11 UPCité - Université Paris Cité
12 CHU Saint-Antoine [AP-HP]
13 ICM - Institut du Cerveau = Paris Brain Institute
14 PASS - Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé
Roseline Vibert
- Function : Author
- PersonId : 1181599
- ORCID : 0000-0001-5202-0212
Chrystelle Colas
- Function : Author
Albain Chansavang
- Function : Author
- PersonId : 1252741
- ORCID : 0000-0002-9835-2156
Alex Duval
- Function : Author
- PersonId : 1226785
- ORCID : 0000-0003-1534-1724
Pierre Laurent-Puig
- Function : Author
- PersonId : 757353
- ORCID : 0000-0001-8475-5459
- IdRef : 071013512
Franck Bielle
- Function : Author
- PersonId : 1221460
- ORCID : 0000-0001-6564-6388
- IdRef : 156375389
Romain Nicolle
- Function : Author
- PersonId : 1252742
- ORCID : 0000-0001-8578-9095
Patrick Benusiglio
- Function : Author
- PersonId : 1226061
- ORCID : 0000-0003-1003-1997
- IdRef : 259601357
Abstract
Some patients with Lynch syndrome (LS) have extreme phenotypes, i.e. cancer before the recommended screening age, or cancer for which there are no screening guidelines. We made the hypothesis that additional germline variants in cancer susceptibility genes (CSG) could explain some of these phenotypes. We compared the prevalence of additional CSG variants in LS patients with a cancer diagnosis before age 30 (early-onset, EO group) and after 40 (usual-onset, UO group). While there was no overall difference, we did find an excess of pathogenic variants and variants of unknown significance in EO cases when only gastrointestinal CSG were considered (OR 2.25; 95% CI: 1.01-5.06, p value = 0.04). Four EO cases stood out: two with POLE/POLD1 variants in the key exonuclease domain, one with a BMPR1A duplication and one with an EPCAM deletion. Additional germline variants should be considered in future screening recommendations, as they might influence cancer risk.