TY - JOUR
T1 - B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS
AU - Wang, Sophia S.
AU - Vajdic, Claire M.
AU - Linet, Martha S.
AU - Slager, Susan L.
AU - Voutsinas, Jenna
AU - Nieters, Alexandra
AU - Casabonne, Delphine
AU - Cerhan, James R.
AU - Cozen, Wendy
AU - Alarcón, Graciela
AU - Martínez-Maza, Otoniel
AU - Brown, Elizabeth E.
AU - Bracci, Paige M.
AU - Turner, Jennifer
AU - Hjalgrim, Henrik
AU - Bhatti, Parveen
AU - Zhang, Yawei
AU - Birmann, Brenda M.
AU - Flowers, Christopher R.
AU - Paltiel, Ora
AU - Holly, Elizabeth A.
AU - Kane, Eleanor
AU - Weisenburger, Dennis D.
AU - Maynadié, Marc
AU - Cocco, Pierluigi
AU - Foretova, Lenka
AU - Breen, Elizabeth Crabb
AU - Lan, Qing
AU - Brooks-Wilson, Angela
AU - De Roos, Anneclaire J.
AU - Smith, Martyn T.
AU - Roman, Eve
AU - Boffetta, Paolo
AU - Kricker, Anne
AU - Zheng, Tongzhang
AU - Skibola, Christine F.
AU - Clavel, Jacqueline
AU - Monnereau, Alain
AU - Chanock, Stephen J.
AU - Rothman, Nathaniel
AU - Benavente, Yolanda
AU - Hartge, Patricia
AU - Smedby, Karin E.
N1 - Publisher Copyright:
© 2022 The Authors; Published by the American Association for Cancer Research
PY - 2022/5
Y1 - 2022/5
N2 - 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 ¼ 1,914), follicular lymphoma (n ¼ 1,733), and marginal zone lymphoma (MZL; n ¼ 407), using unconditional logistic regression. Results: We demonstrated a positive association of DLBCL PRS with DLBCL risk [T2 vs. T1: OR ¼ 1.24; 95% confidence interval (CI), 1.08–1.43; T3 vs. T1: OR ¼ 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 ¼ 6.46 vs. no autoimmune condition and a T1 PRS, Ptrend < 0.0001, P-interaction (Pinteraction) ¼ 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.
AB - 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 ¼ 1,914), follicular lymphoma (n ¼ 1,733), and marginal zone lymphoma (MZL; n ¼ 407), using unconditional logistic regression. Results: We demonstrated a positive association of DLBCL PRS with DLBCL risk [T2 vs. T1: OR ¼ 1.24; 95% confidence interval (CI), 1.08–1.43; T3 vs. T1: OR ¼ 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 ¼ 6.46 vs. no autoimmune condition and a T1 PRS, Ptrend < 0.0001, P-interaction (Pinteraction) ¼ 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.
UR - http://www.scopus.com/inward/record.url?scp=85130190242&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-21-0875
DO - 10.1158/1055-9965.EPI-21-0875
M3 - Article
C2 - 35244686
AN - SCOPUS:85130190242
SN - 1055-9965
VL - 31
SP - 1103
EP - 1110
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 5
ER -