Breen, Elizabeth Crabb
Mayo Clinic
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Citations 1
B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS
Wang, Sophia , Vajdic, Claire M. , Linet, Martha S. , Slager, Susan L. , Nieters, Alexandra, Casabonne, Delphine , Cerhan, James R. , Cozen, Wendy , Brown, Elizabeth E. , Bracci, Paige M. , Turner, Jennifer , Hjalgrim, Henrik , Bhatti, Parveen , Flowers, Christopher R. , Paltiel, Ora , Holly, Elizabeth A., Weisenburger, Dennis D. , Cocco, Pierluigi , Breen, Elizabeth C. , Lan, Qing , Roos, Anneclaire J. De , Smith, Martyn T. , Kricker, Anne , Zheng, Tongzhang, Skibola, Christine F., Clavel, Jacqueline , Monnereau, Alain, Rothman, Nathaniel , Benavente, Yolanda , Hartge, Patricia, Smedby, Karin E. , Monnereau, Alain , Wang, Sophia S , Cerhan, James R , Cozen, Wendy , Martínez-Maza, Otoniel , Turner, Jennifer , Hjalgrim, Henrik , Bhatti, Parveen , Birmann, Brenda M , Kane, Eleanor , Weisenburger, Dennis D , Maynadié, Marc , Cocco, Pierluigi , Breen, Elizabeth Crabb , Lan, Qing , Brooks-Wilson, Angela R , Roman, Eve , Boffetta, Paolo , Kricker, Anne , Clavel, Jacqueline , Vajdic, Claire M , De Roos, Anneclaire J , Slager, Susan L , Voutsinas, Jenna M. , Alarcón, Graciela S. , Martı́nez-Maza, Otoniel , Zhang, Yawei , Birmann, Brenda M. , Kane, Eleanor , Foretová, Lenka , Brooks‐Wilson, Angela , Roman, Eve , Chanock, Stephen Jacob , Rothman, Nathaniel
Cancer Epidemiology, Biomarkers & Prevention | May 4, 2022 | Volume: 31 | Issue: 5 | Pages: 1103-1110
Abstract 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.