Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis

Geffen Kleinstern Nicola Camp Lynn Goldin 1 Celine Vachon Claire Vajdic Silvia de Sanjosé 2 J. Brice Weinberg Yolanda Benavente 3 Delphine Casabonne Mark Liebow Alexandra Nieters 4 Henrik Hjalgrim Mads Melbye 5 Bengt Glimelius 6 Hans-Olov Adami 7 Paolo Boffetta 8 Paul Brennan 9 Marc Maynadié 10, 11, 12 James Mckay 13 Pier Luigi Cocco Tait Shanafelt 14 Timothy Call Aaron Norman 15 Curtis Hanson Dennis Robinson Kari Chaffee Angela Brooks-Wilson Alain Monnereau 16, 17, 18 Jacqueline Clavel 17, 18 Martha Glenn 19 Karen Curtin 19 Lucia Conde Paige Bracci Lindsay Morton 1 Wendy Cozen 20 Richard Severson 21 Stephen Chanock 22 John Spinelli James Johnston Nathaniel Rothman 23 Christine Skibola 24 Jose Leis Neil Kay Karin Smedby 25 Sonja Berndt 23 James Cerhan 14 Neil Caporaso 23 Susan Slager 26, 14
17 EPICENE - Cancer environnement
BPH - Bordeaux population health
18 CRESS - U1153 - Equipe 7 : EPICEA - Epidémiologie des cancers de l'enfant et de l'adolescent
UPD5 - Université Paris Descartes - Paris 5, CRESS (U1153 / UMR_A 1125) - Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité
Abstract : Inherited loci have been found to be associated with risk of chronic lymphocytic leukemia (CLL). A combined polygenic risk score (PRS) of representative single nucleotide polymorphisms (SNPs) from these loci may improve risk prediction over individual SNPs. Herein, we evaluated the association of a PRS with CLL risk and its precursor, monoclonal B-cell lymphocytosis (MBL). We assessed its validity and discriminative ability in an independent sample and evaluated effect modification and confounding by family history (FH) of hematological cancers. For discovery, we pooled genotype data on 41 representative SNPs from 1499 CLL and 2459 controls from the InterLymph Consortium. For validation, we used data from 1267 controls from Mayo Clinic and 201 CLL, 95 MBL, and 144 controls with a FH of CLL from the Genetic Epidemiology of CLL Consortium. We used odds ratios (ORs) to estimate disease associations with PRS and c-statistics to assess discriminatory accuracy. In InterLymph, the continuous PRS was strongly associated with CLL risk (OR, 2.49; P = 4.4 × 10-94). We replicated these findings in the Genetic Epidemiology of CLL Consortium and Mayo controls (OR, 3.02; P = 7.8 × 10-30) and observed high discrimination (c-statistic = 0.78). When jointly modeled with FH, PRS retained its significance, along with FH status. Finally, we found a highly significant association of the continuous PRS with MBL risk (OR, 2.81; P = 9.8 × 10-16). In conclusion, our validated PRS was strongly associated with CLL risk, adding information beyond FH. The PRS provides a means of identifying those individuals at greater risk for CLL as well as those at increased risk of MBL, a condition that has potential clinical impact beyond CLL.
Type de document :
Article dans une revue
Liste complète des métadonnées

https://hal-univ-bourgogne.archives-ouvertes.fr/hal-02066279
Contributeur : Lnc - Université de Bourgogne <>
Soumis le : mercredi 13 mars 2019 - 11:58:12
Dernière modification le : mardi 13 août 2019 - 10:56:05

Lien texte intégral

Identifiants

Citation

Geffen Kleinstern, Nicola Camp, Lynn Goldin, Celine Vachon, Claire Vajdic, et al.. Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis. Blood, American Society of Hematology, 2018, 131 (23), pp.2541-2551. ⟨http://www.bloodjournal.org/content/131/23/2541.long?sso-checked=true⟩. ⟨10.1182/blood-2017-11-814608⟩. ⟨hal-02066279⟩

Partager

Métriques

Consultations de la notice

37