Journal article
B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS
Cancer epidemiology, biomarkers & prevention, Vol.31(5), pp.1103-1110
05/04/2022
DOI: 10.1158/1055-9965.EPI-21-0875
PMCID: PMC9081255
PMID: 35244686
Abstract
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.
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.
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.
Our results suggest that PRS constructed from currently known subtype-specific loci may not necessarily capture biological pathways shared with autoimmune conditions.
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.
Details
- Title: Subtitle
- B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS
- Creators
- Sophia S Wang - City Of Hope National Medical CenterClaire M Vajdic - UNSW SydneyMartha S Linet - National Cancer InstituteSusan L Slager - Mayo Clinic, Rochester, MN, United States.Jenna Voutsinas - City Of Hope National Medical CenterAlexandra Nieters - University of FreiburgDelphine Casabonne - Centro de Investigación Biomédica en Red de Epidemiología y Salud PúblicaJames R Cerhan - Mayo Clinic, Rochester, MN, United States.Wendy Cozen - University of California, IrvineGraciela Alarcón - University of Alabama at Birmingham HospitalOtoniel Martínez-Maza - University of California, Los AngelesElizabeth E Brown - University of Alabama at BirminghamPaige M Bracci - University of California, San FranciscoJennifer Turner - Douglass Hanly Moir PathologyHenrik Hjalgrim - Statens Serum InstitutParveen Bhatti - BC Cancer Research CentreYawei Zhang - Department of Cancer Prevention and Control at the National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, China.Brenda M Birmann - Brigham and Women's HospitalChristopher R Flowers - The University of Texas MD Anderson Cancer CenterOra Paltiel - Hadassah Medical CenterElizabeth A Holly - University of California, San FranciscoEleanor Kane - University of YorkDennis D Weisenburger - City Of Hope National Medical CenterMarc Maynadié - Université de BourgognePierluigi Cocco - University of CagliariLenka Foretova - Masaryk Memorial Cancer InstituteElizabeth Crabb Breen - University of California, Los AngelesQing Lan - National Cancer InstituteAngela Brooks-Wilson - Simon Fraser UniversityAnneclaire J De Roos - Drexel UniversityMartyn T Smith - University of California, BerkeleyEve Roman - University of YorkPaolo Boffetta - Stony Brook UniversityAnne Kricker - University of SydneyTongzhang Zheng - Brown UniversityChristine F Skibola - Emory UniversityJacqueline Clavel - Université Paris CitéAlain Monnereau - Sorbonne Paris CitéStephen J Chanock - National Cancer InstituteNathaniel Rothman - National Cancer InstituteYolanda Benavente - Catalan Institut of Oncology, IDIBELL, Barcelona, Spain.Patricia Hartge - National Cancer InstituteKarin E Smedby - Karolinska Institutet
- Resource Type
- Journal article
- Publication Details
- Cancer epidemiology, biomarkers & prevention, Vol.31(5), pp.1103-1110
- DOI
- 10.1158/1055-9965.EPI-21-0875
- PMID
- 35244686
- PMCID
- PMC9081255
- ISSN
- 1055-9965
- eISSN
- 1538-7755
- Grant note
- R01 CA069069 / NCI NIH HHS R03 CA179558 / NCI NIH HHS CIHR P30 CA015083 / NCI NIH HHS P50 CA097274 / NCI NIH HHS
- Language
- English
- Date published
- 05/04/2022
- Academic Unit
- Epidemiology
- Record Identifier
- 9984368206202771
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