Fiche publication
Date publication
avril 2018
Journal
Blood
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MAYNADIE Marc
Tous les auteurs :
Kleinstern G, Camp NJ, Goldin LR, Vachon CM, Vajdic CM, de Sanjose S, Weinberg JB, Benavente Y, Casabonne D, Liebow M, Nieters A, Hjalgrim H, Melbye M, Glimelius B, Adami HO, Boffetta P, Brennan P, Maynadie M, McKay J, Cocco PL, Shanafelt TD, Call TG, Norman A, Hanson C, Robinson D, Chaffee KG, Brooks-Wilson AR, Monnereau A, Clavel J, Glenn M, Curtin K, Conde L, Bracci PM, Morton LM, Cozen W, Severson RK, Chanock SJ, Spinelli JJ, Johnston JB, Rothman N, Skibola CF, Leis JF, Kay NE, Smedby KE, Berndt SI, Cerhan JR, Caporaso N, Slager SL
Lien Pubmed
Résumé
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 1,499 CLLs and 2,459 controls from the InterLymph Consortium. For validation, we utilized data from 1,267 controls from Mayo Clinic and 201 CLLs, 95 MBLs, and 144 controls with FH of CLL from the GEC 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). We replicated these findings in the GEC Consortium and Mayo controls (OR=3.02, P=7.8x10) 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). 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.
Référence
Blood. 2018 Apr 19;:
