Slager, Susan L

Abstract Background: Vaccinations have been hypothesized to play a role in lymphoma etiology, but there are few studies, mixed results, and limited data on lymphoma subtypes. Herein, we investigate the association of vaccinations with risk of major lymphoma subtypes. Methods: We studied 2,461 lymphoma cases and 2,253 controls enrolled from 2002 to 2014. Participants self-reported history of vaccinations against hepatitis A, hepatitis B, yellow fever, and influenza. Polytomous logistic regression was used to estimate OR and 95% confidence intervals (CI), adjusting for potential confounders. Results: After multivariable adjustment, vaccination against influenza was inversely associated with lymphoma (OR = 0.82; 95% CI, 0.66–1.02), which was stronger for last vaccination 1+ years before enrollment (OR = 0.71; 95% CI, 0.56–0.91) and for >5 influenza vaccinations (OR = 0.56; 95% CI, 0.46–0.68). Ever vaccination against hepatitis A (OR = 0.81; 95% CI, 0.66–1.00) but not hepatitis B (OR = 0.97; 95% CI, 0.81–1.18) was associated with lymphoma risk, although more recent vaccinations were inversely associated with lymphoma risk for both hepatitis A (<6 years before enrollment, OR = 0.56; 95% CI, 0.40–0.77) and hepatitis B (<9 years before enrollment, OR = 0.72; 95% CI, 0.55–0.93). Ever vaccination against yellow fever was inversely associated with risk (OR = 0.73; 95% CI, 0.55–0.96), and this did not vary by time since last vaccination. Although there was no overall statistical evidence for heterogeneity of vaccination history by lymphoma subtype, the only statistically significant inverse associations were observed for influenza and yellow fever vaccinations with diffuse large B-cell and follicular lymphoma. Conclusions: Selected vaccinations were inversely associated with lymphoma risk, with time since last vaccination relevant for some of these vaccines. Impact: Vaccinations against hepatitis A, hepatitis B, yellow fever, and influenza are unlikely to increase lymphoma risk.

Abstract Our understanding of familial predisposition to lymphoma (collectively defined as non-Hodgkin lymphoma [NHL], Hodgkin lymphoma [HL], and chronic lymphocytic leukemia [CLL]) outside of rare hereditary syndromes has progressed rapidly during the last decade. First-degree relatives of NHL, HL, and CLL patients have an ∼1.7-fold, 3.1-fold, and 8.5-fold elevated risk of developing NHL, HL, and CLL, respectively. These familial risks are elevated for multiple lymphoma subtypes and do not appear to be confounded by nongenetic risk factors, suggesting at least some shared genetic etiology across the lymphoma subtypes. However, a family history of a specific subtype is most strongly associated with risk for that subtype, supporting subtype-specific genetic factors. Although candidate gene studies have had limited success in identifying susceptibility loci, genome-wide association studies (GWAS) have successfully identified 67 single nucleotide polymorphisms from 41 loci, predominately associated with specific subtypes. In general, these GWAS-discovered loci are common (minor allele frequency >5%), have small effect sizes (odds ratios, 0.60-2.0), and are of largely unknown function. The relatively low incidence of lymphoma, modest familial risk, and the lack of a screening test and associated intervention, all argue against active clinical surveillance for lymphoma in affected families at this time.