Abstract
BackgroundNon-Hodgkin lymphoma (NHL) is a malignancy etiologically linked to immunomodulatory exposures and disorders. Endogenous female sex hormones may modify immune function and influence NHL risk. Few studies have examined associations between reproductive factors, which can serve as surrogates for such hormonal exposures, and NHL risk by subtype.Methodology/Principal FindingsWomen in the California Teachers Study cohort provided detailed data in 1995–1996 on reproductive history. Follow-up through 2007 identified 574 women with incident B-cell NHL. Hazard rate ratios (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models to assess associations between reproductive factors and all B-cell NHL combined, diffuse large B-cell lymphomas, follicular lymphomas, and B-cell chronic lymphocytic leukemias/small lymphocytic lymphomas. Pregnancy was marginally associated with lower risk of B-cell NHL (RR = 0.84, 95% CI = 0.68–1.04). Much of the reduction in risk was observed after one full-term pregnancy relative to nulligravid women (RR = 0.75, 95% CI = 0.54–1.06; P for trend <0.01), particularly for diffuse large B-cell lymphomas (P for trend = 0.13), but not among women who had only incomplete pregnancies. Age at first full-term pregnancy was marginally inversely associated with B-cell NHL risk overall (P for trend = 0.08) and for diffuse large B-cell lymphomas (P for trend = 0.056). Breast feeding was not associated with B-cell NHL risk overall or by subtype.ConclusionsFull-term pregnancy and early age at first full-term pregnancy account for most of the observed reduction in B-cell NHL risk associated with gravidity. Pregnancy-related hormonal exposures, including prolonged and high-level exposure to progesterone during a full-term pregnancy may inhibit development of B-cell NHL.
Highlights
Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of lymphoid malignancies
Full-term pregnancy and early age at first full-term pregnancy account for most of the observed reduction in B-cell NHL risk associated with gravidity
Because women generally have lower incidence rates of most NHL subtypes than men [5] and sex hormones have profound effects on the immune system [6], we hypothesized that endogenous estrogen exposure would confer a reduced risk of Bcell NHL
Summary
Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of lymphoid malignancies. In the US, NHL incidence rates have risen steadily since the early 1940s [1], such that NHL is the fifth most common cancer among US men and women [2]. The observation that men have consistently higher incidence rates of NHL than women [5], coupled with biological evidence that sex steroid hormones modulate the immune system [6], suggests a potential influence of endogenously produced female hormones on lymphomagenesis. Lee et al [12] found that women with four or more pregnancies had decreased risk of diffuse large-cell lymphoma (defined by the REAL classification [19], and not limited to B-cell NHL) compared to women who had never been pregnant. In contrast to these case-control studies, a recent cohort study [16]. Few studies have examined associations between reproductive factors, which can serve as surrogates for such hormonal exposures, and NHL risk by subtype
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