期刊
BLOOD
卷 131, 期 23, 页码 2541-2551出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2017-11-814608
关键词
-
类别
资金
- National Institutes of Health, National Cancer Institute [CA134674, 118444, CA1046282, CA154643, 5R01 CA69669-02, CA97274, R25 CA92049]
- HCI Comprehensive Cancer Center Support grant [P30 CA42014]
- National Institutes of Health, National Cancer Institute Surveillance, Epidemiology, and End Results Program (SEER) Program [HHSN261201000026C]
- Utah State Department of Health
- University of Utah
- Canadian Institutes for Health Research
- Canadian Cancer Society
- Michael Smith Foundation for Health Research
- California Department of Health Services [103885]
- National Cancer Institute's SEER Program [HHSN261201000140C]
- University of Southern California [HHSN261201000035C, HHSN261201000034C]
- Centers for Disease Control and Prevention's National Program of Cancer Registries [1U58 DP000807-01]
- European Commission [QLK4-CT-2000-00422, FOOD-CT-2006-023103]
- Spanish Ministry of Health CIBER de Epidemiologia y Salud Publica [PI11/01810, PI14/01219, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095]
- Marato de TV3 Foundation [051210]
- Agencia de Gestiod'AjutsUniversitarisi de Recerca - Generalitat de Catalunya [2014SRG756]
- National Institutes of Health [NO1-CO-12400]
- Compagnia di San Paolo-Programma Oncologia
- Federal Office for Radiation Protection [StSch4261, StSch4420]
- Jose Carreras Leukemia Foundation [DJCLS-R12/23]
- German Federal Ministry for Education and Research [BMBF-01-EO-1303]
- Health Research Board, Ireland
- Cancer Research Ireland
- Fondation de France
- Association de Recherche Contre le Cancer
- MH CZ-DRO (Masaryk Memorial Cancer Institute) [00209805]
- Regional Centre for Applied Molecular Oncology [CZ.1.05/2.1.00/03.0101]
- Association pour la Recherche contre le Cancer
- Institut National du Cancer
- Fondation contre la Leucemie
- Agence nationale de securite sanitaire de l'alimentation
- Swedish Cancer Society [2009/659, 02 6661]
- Stockholm County Council [20110209]
- Strategic Research Program in Epidemiology at Karolinska Institute
- Plan Denmark
- Specialized Programs of Research Excellence in Human Cancer [P50 CA97274]
- Molecular Epidemiology of Non-Hodgkin Lymphoma Survival [R01 CA129539]
- Henry J. Predolin Foundation [R01 CA92153]
- National Center for Advancing Translational Science [UL1 TR000135]
- Mayo Clinic Cancer Center [P30 CA15083]
- Intramural Research Program of the National Cancer Institute, National Institutes of Health
- Public Health Service [N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105]
- Australian National Health and Medical Research Council [ID990920]
- Cancer Council NSW
- University of Sydney Faculty of Medicine
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 = 4.4x10(-94)). We replicated these findings in the Genetic Epidemiology of CLL Consortium and Mayo controls (OR, 3.02; P = 7.8 x 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 x10(-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据