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B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS
SS. Wang, CM. Vajdic, MS. Linet, SL. Slager, J. Voutsinas, A. Nieters, D. Casabonne, JR. Cerhan, W. Cozen, G. Alarcón, O. Martínez-Maza, EE. Brown, PM. Bracci, J. Turner, H. Hjalgrim, P. Bhatti, Y. Zhang, BM. Birmann, CR. Flowers, O. Paltiel, EA....
Language English Country United States
Document type Journal Article
Grant support
R03 CA179558
NCI NIH HHS - United States
R01 CA069069
NCI NIH HHS - United States
CIHR - Canada
NLK
Free Medical Journals
from 1991 to 1 year ago
Freely Accessible Science Journals
from 1991 to 12 months ago
Open Access Digital Library
from 1991-11-01
Open Access Digital Library
from 1991-11-01
- MeSH
- Autoimmune Diseases * epidemiology genetics MeSH
- B-Lymphocytes MeSH
- Genome-Wide Association Study MeSH
- Lymphoma, Large B-Cell, Diffuse * epidemiology genetics MeSH
- Lymphoma, Follicular * epidemiology genetics MeSH
- Humans MeSH
- Case-Control Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: A previous International Lymphoma Epidemiology (InterLymph) Consortium evaluation of joint associations between five immune gene variants and autoimmune conditions reported interactions between B-cell response-mediated autoimmune conditions and the rs1800629 genotype on risk of B-cell non-Hodgkin lymphoma (NHL) subtypes. Here, we extend that evaluation using NHL subtype-specific polygenic risk scores (PRS) constructed from loci identified in genome-wide association studies of three common B-cell NHL subtypes. METHODS: In a pooled analysis of NHL cases and controls of Caucasian descent from 14 participating InterLymph studies, we evaluated joint associations between B-cell-mediated autoimmune conditions and tertile (T) of PRS for risk of diffuse large B-cell lymphoma (DLBCL; n = 1,914), follicular lymphoma (n = 1,733), and marginal zone lymphoma (MZL; n = 407), using unconditional logistic regression. RESULTS: We demonstrated a positive association of DLBCL PRS with DLBCL risk [T2 vs. T1: OR = 1.24; 95% confidence interval (CI), 1.08-1.43; T3 vs. T1: OR = 1.81; 95% CI, 1.59-2.07; P-trend (Ptrend) < 0.0001]. DLBCL risk also increased with increasing PRS tertile among those with an autoimmune condition, being highest for those with a B-cell-mediated autoimmune condition and a T3 PRS [OR = 6.46 vs. no autoimmune condition and a T1 PRS, Ptrend < 0.0001, P-interaction (Pinteraction) = 0.49]. Follicular lymphoma and MZL risk demonstrated no evidence of joint associations or significant Pinteraction. CONCLUSIONS: Our results suggest that PRS constructed from currently known subtype-specific loci may not necessarily capture biological pathways shared with autoimmune conditions. IMPACT: Targeted genetic (PRS) screening among population subsets with autoimmune conditions may offer opportunities for identifying those at highest risk for (and early detection from) DLBCL.
British Columbia Cancer Research Center Vancouver British Columbia Canada
Centre of Research in Epidemiology and Statistics UMR1153 INSERM Université de Paris Paris France
Chao Family Comprehensive Cancer Center University of California Irvine Irvine California
Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Epidemiology Research Statens Serum Institut Copenhagen Denmark
Department of Epidemiology School of Public Health Brown University Providence Rhode Island
Department of Health Sciences Research Mayo Clinic Rochester Minnesota
Department of Health Sciences University of York York United Kingdom
Department of Histopathology Douglass Hanly Moir Pathology Sydney New South Wales Australia
Department of Medical and Surgical Sciences University of Bologna Bologna Italy
Department of Pathology City of Hope Duarte California
Faculty of Medicine Health and Human Sciences Macquarie University Sydney New South Wales Australia
O'Neal Comprehensive Cancer Center The University of Alabama at Birmingham Birmingham Alabama
Stony Brook Cancer Center Stony Brook University Stony Brook New York
Sydney School of Public Health The University of Sydney Sydney New South Wales Australia
The Biomedical Research Centre Network for Epidemiology and Public Health Madrid Spain
The Center for Chronic Immunodeficiency University Medical Center Freiburg Freiburg Germany
References provided by Crossref.org
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