Markers of B-cell activation in relation to risk of non-Hodgkin lymphoma

Abstract

B-cell activation biomarkers have been associated with increased risk of non-Hodgkin lymphoma (NHL) in HIV-infected populations. However, whether a similar association may exist in general populations has not been established. We conducted a case-control study within the Women's Health Initiative Observational Study cohort to measure the B-cell activation biomarkers sCD23, sCD27, sCD30, sCD44, and CXCL13 in serum samples collected an average of 6 years before NHL diagnosis in 491 cases and 491 controls. Using logistic regression to estimate odds ratios, we observed strong associations between NHL and markers for all B-cell NHL and for major subtypes. Women with marker levels in the highest-versus-lowest quartile categories of CD23, CD27, CD30, or CXCL13 were at 2.8- to 5.5-fold increased risk of B-NHL. In addition, there were significant trends of risk with increasing levels of these markers present. Associations were strongest for cases with shortest lag times between blood draw and diagnosis (<3 years). However, there were also significant associations for cases with the longest prediagnostic lag (9 to 13 years). Taken together, our findings indicate a prominent role for B-cell activation among postmenopausal women in the etiology of B-cell NHL and/or in processes reflective of early disease development as early as 9 years before diagnosis.

Figure 1

CLL/SLL/PLL risk associated with 1-unit (natural log scale) increase in immune marker level (OR and 95% CI), with cases categorized by decreasing lag time between blood draw and diagnosis (circle: 9–13 years; triangle: <3 years).

Figure 2

DLBCL risk associated with 1-unit (natural log scale) increase in immune marker level (OR and 95% CI), with cases categorized by decreasing lag time between blood draw and diagnosis (circle: 9–13 years; triangle: <3 years).

Figure 3

Follicular lymphoma risk associated with 1-unit (natural log scale) increase in immune marker level (OR and 95% CI), with cases categorized by decreasing lag time between blood draw and diagnosis (circle: 9–13 years; triangle: <3 years).