Paltiel, Ora

Summary Among individuals of European Ancestry (EA), genome‐wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) and polygenic risk scores (PRSs) associated with non‐Hodgkin lymphoma (NHL) risk. We evaluated subtype‐specific PRSs, based on established EA‐SNPs, in Israeli Jews (IJ) and Palestinian Arabs (PA) and performed a GWAS in the combined ethnic groups to identify new loci. We included three common pathologically confirmed subtypes: diffuse large B‐cell (DLBCL), follicular (FL) and marginal zone (MZL) lymphomas. Controls were frequency matched to cases by age and sex. Among 752 IJ (201—DLBCL; 130—FL; 54—MZL/367—controls) and 593 PA (203—DLBCL; 41—FL/349‐controls), we computed PRSs weighted by EA‐derived effect estimates and used logistic regression models adjusted for confounders. In the combined ethnic groups of IJ and PA, subtype‐specific PRSs were significantly associated with the corresponding subtype, with a 1.69‐fold, 2.21‐fold and 2.26‐fold risk for DLBCL, FL and MZL, respectively; however, these effect sizes were attenuated compared to those reported in EA and varied by ethnicity. In the GWAS of the combined ethnic groups, two novel SNPs in the 6p21.32 locus were associated with DLBCL risk. Additional GWAS studies are needed among Jewish and Arab populations to improve genetic risk prediction for NHL in these ethnic groups.

AbstractNon‐Hodgkin lymphoma (NHL) is composed of a heterogeneous collection of subtypes with considerable differences in genetics, biology and aetiology. Studies to date on physical activity and NHL risk have not had sufficient sample size to evaluate whether associations differ by subtype. We pooled data from nine case‐control studies to examine the association between moderate‐to‐vigorous intensity physical activity (MVPA) and risk of NHL overall and by subtype (diffuse large B‐cell lymphoma, follicular lymphoma, chronic lymphocytic leukaemia/small lymphocytic lymphoma, marginal zone lymphoma and mature T‐cell lymphoma). A total of 5653 cases and 9115 controls were included in the pooled analysis. Physical activity was harmonised across nine studies and modelled as study‐specific tertiles. Multinomial logistic regression was used to estimate the association between physical activity and NHL, adjusting for confounders. The overall odds of NHL was 13% lower among participants in the most active tertile of MVPA compared to the least active tertile (adjusted odds ratio = 0.87, 95% CI = 0.80, 0.95). Similar decreases were observed across NHL subtypes. In summary, in this pooled analysis of case‐control studies, physical activity was associated with a modest risk reduction for each NHL subtype examined and with overall NHL.