Birth order, allergies and lymphoma risk: Results of the European collaborative research project Epilymph

Abstract

Lymphomas are a heterogeneous group of malignancies of the immune system. Recent studies suggest that immunological conditions which are modulated by lifestyle-dependent environmental determinants might affect lymphoma risk. We used data from Epilymph, a European multi-centric case–control study with 2480 cases and 2540 controls, to analyse the relationship between lifestyle-dependent immunological determinants and risk of lymphomas. We found an inverse relationship between risk of lymphoma and allergies, mainly respiratory (OR = 0.86, CI = 0.89–1.01) and food allergies (OR = 0.67, CI = 0.52–0.85), a slightly elevated lymphoma risk for first-born children (OR = 1.17, CI = 0.99–1.39) and only children (OR = 1.10, CI = 0.86–1.39). The inverse relationship between atopic disorders and risk of lymphomas is consistent with earlier observations. Our findings on birth order and lymphoma increase the inconsistency of findings across studies and suggest a critical reappraisal of potential underlying mechanisms.

Introduction

Lymphomas are a heterogeneous group of malignant diseases of cells of the immune system. The best established risk factors are those related to down-regulation of immune function, e.g. genetically determined or acquired immune deficiencies including HIV infection or iatrogenically induced immune suppression after transplantation. Recent studies suggest that risk might additionally be affected by immunological conditions, themselves modulated by life-style or culturally determined (e.g., family size, hygienic circumstances, outlined in the so called “hygiene hypothesis, for summary see [1]). Epidemiologically testable indicators of this hypothesis include birth order, assumed to be an indicator for variation in early-life exposure to infection, and a history of allergies as an indicator for lifestyle-related altered immune responsiveness.

Although this hypothesis is conceptually striking, current evidence supporting it appears inconclusive. While several studies have found increasing adulthood lymphoma risk with increasing sibship size or birth order [1], [2], [3], [4], others have found no association [5], [6], [7] or opposite results [8], [9].

The association to allergic disorders appears more conclusive: several studies have shown a statistically significantly reduced risk, some an insignificantly decreased risk or null result, but none have reported an elevated lymphoma risk associated with allergies (for details see [1]).

A limitation of many studies was the comparatively small study size largely preventing detailed analyses of different lymphoma entities, which would be appropriate given the heterogeneity of the disease. Here, we present results on the relationship between birth order and allergies and lymphoma risk in Epilymph. This large European collaborative research effort with about 2500 lymphoma cases and 2500 hospital or population controls allows for the analysis of entity-specific associations.