B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS

Sophia S. Wang; Claire M. Vajdic; Martha S. Linet; Susan L. Slager; Jenna Voutsinas; Alexandra Nieters; Delphine Casabonne; James R. Cerhan; Wendy Cozen; Graciela Alarcón; Otoniel Martínez-Maza; Elizabeth E. Brown; Paige M. Bracci; Jennifer Turner; Henrik Hjalgrim; Parveen Bhatti; Yawei Zhang; Brenda M. Birmann; Christopher R. Flowers; Ora Paltiel; Elizabeth A. Holly; Eleanor Kane; Dennis D. Weisenburger; Marc Maynadié; Pierluigi Cocco; Lenka Foretova; Elizabeth Crabb Breen; Qing Lan; Angela Brooks-Wilson; Anneclaire J. De Roos; Martyn T. Smith; Eve Roman; Paolo Boffetta; Anne Kricker; Tongzhang Zheng; Christine F. Skibola; Jacqueline Clavel; Alain Monnereau; Stephen J. Chanock; Nathaniel Rothman; Yolanda Benavente; Patricia Hartge; Karin E. Smedby

doi:10.1158/1055-9965.EPI-21-0875

B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS

Sophia S. Wang, Claire M. Vajdic, Martha S. Linet, Susan L. Slager, Jenna Voutsinas, Alexandra Nieters, Delphine Casabonne, James R. Cerhan, Wendy Cozen, Graciela Alarcón, Otoniel Martínez-Maza, Elizabeth E. Brown, Paige M. Bracci, Jennifer Turner, Henrik Hjalgrim, Parveen Bhatti, Yawei Zhang, Brenda M. Birmann, Christopher R. Flowers, Ora PaltielElizabeth A. Holly, Eleanor Kane, Dennis D. Weisenburger, Marc Maynadié, Pierluigi Cocco, Lenka Foretova, Elizabeth Crabb Breen, Qing Lan, Angela Brooks-Wilson, Anneclaire J. De Roos, Martyn T. Smith, Eve Roman, Paolo Boffetta, Anne Kricker, Tongzhang Zheng, Christine F. Skibola, Jacqueline Clavel, Alain Monnereau, Stephen J. Chanock, Nathaniel Rothman, Yolanda Benavente, Patricia Hartge, Karin E. Smedby

Health Sciences

Research output: Contribution to journal › Article › peer-review

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\CI), 1.08–1.43; T3 vs. T1: OR = 1.81; 95\ 1.59–2.07; P-trend (Ptrend) \lt; 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 \lt; 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.

Original language	English
Pages (from-to)	1103-1110
Number of pages	8
Journal	Cancer Epidemiology Biomarkers & Prevention
Volume	31
Issue number	5
DOIs	https://doi.org/10.1158/1055-9965.EPI-21-0875
Publication status	Published - 4 May 2022

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10.1158/1055-9965.EPI-21-0875Licence: CC BY-NC-ND

B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS
© 2022 The Authors
Final published version, 250 KBLicence: CC BY-NC-ND

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Wang, S. S., Vajdic, C. M., Linet, M. S., Slager, S. L., Voutsinas, J., Nieters, A., Casabonne, D., Cerhan, J. R., Cozen, W., Alarcón, G., Martínez-Maza, O., Brown, E. E., Bracci, P. M., Turner, J., Hjalgrim, H., Bhatti, P., Zhang, Y., Birmann, B. M., Flowers, C. R., ... Smedby, K. E. (2022). B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS. Cancer Epidemiology Biomarkers & Prevention, 31(5), 1103-1110. https://doi.org/10.1158/1055-9965.EPI-21-0875

@article{2dfd95b7486641718d77f29a22d2278a,

title = "B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS",

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\CI), 1.08–1.43; T3 vs. T1: OR = 1.81; 95\ 1.59–2.07; P-trend (Ptrend) \lt; 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 \lt; 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.",

author = "Wang, {Sophia S.} and Vajdic, {Claire M.} and Linet, {Martha S.} and Slager, {Susan L.} and Jenna Voutsinas and Alexandra Nieters and Delphine Casabonne and Cerhan, {James R.} and Wendy Cozen and Graciela Alarc{\'o}n and Otoniel Mart{\'i}nez-Maza and Brown, {Elizabeth E.} and Bracci, {Paige M.} and Jennifer Turner and Henrik Hjalgrim and Parveen Bhatti and Yawei Zhang and Birmann, {Brenda M.} and Flowers, {Christopher R.} and Ora Paltiel and Holly, {Elizabeth A.} and Eleanor Kane and Weisenburger, {Dennis D.} and Marc Maynadi{\'e} and Pierluigi Cocco and Lenka Foretova and Breen, {Elizabeth Crabb} and Qing Lan and Angela Brooks-Wilson and {De Roos}, {Anneclaire J.} and Smith, {Martyn T.} and Eve Roman and Paolo Boffetta and Anne Kricker and Tongzhang Zheng and Skibola, {Christine F.} and Jacqueline Clavel and Alain Monnereau and Chanock, {Stephen J.} and Nathaniel Rothman and Yolanda Benavente and Patricia Hartge and Smedby, {Karin E.}",

note = "{\textcopyright} 2022 The Authors",

year = "2022",

month = may,

day = "4",

doi = "10.1158/1055-9965.EPI-21-0875",

language = "English",

volume = "31",

pages = "1103--1110",

journal = "Cancer Epidemiology Biomarkers & Prevention",

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Wang, SS, Vajdic, CM, Linet, MS, Slager, SL, Voutsinas, J, Nieters, A, Casabonne, D, Cerhan, JR, Cozen, W, Alarcón, G, Martínez-Maza, O, Brown, EE, Bracci, PM, Turner, J, Hjalgrim, H, Bhatti, P, Zhang, Y, Birmann, BM, Flowers, CR, Paltiel, O, Holly, EA, Kane, E, Weisenburger, DD, Maynadié, M, Cocco, P, Foretova, L, Breen, EC, Lan, Q, Brooks-Wilson, A, De Roos, AJ, Smith, MT, Roman, E, Boffetta, P, Kricker, A, Zheng, T, Skibola, CF, Clavel, J, Monnereau, A, Chanock, SJ, Rothman, N, Benavente, Y, Hartge, P & Smedby, KE 2022, 'B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS', Cancer Epidemiology Biomarkers & Prevention, vol. 31, no. 5, pp. 1103-1110. https://doi.org/10.1158/1055-9965.EPI-21-0875

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.

PY - 2022/5/4

Y1 - 2022/5/4

N2 - 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\CI), 1.08–1.43; T3 vs. T1: OR = 1.81; 95\ 1.59–2.07; P-trend (Ptrend) \lt; 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 \lt; 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.

AB - 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\CI), 1.08–1.43; T3 vs. T1: OR = 1.81; 95\ 1.59–2.07; P-trend (Ptrend) \lt; 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 \lt; 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.

U2 - 10.1158/1055-9965.EPI-21-0875

DO - 10.1158/1055-9965.EPI-21-0875

M3 - Article

SN - 1055-9965

VL - 31

SP - 1103

EP - 1110

JO - Cancer Epidemiology Biomarkers & Prevention

JF - Cancer Epidemiology Biomarkers & Prevention

IS - 5

ER -