Research Article: Reproductive Factors and Non-Hodgkin Lymphoma Risk in the California Teachers Study

Date Published: December 2, 2009

Publisher: Public Library of Science

Author(s): Jennifer Prescott, Yani Lu, Ellen T. Chang, Jane Sullivan-Halley, Katherine D. Henderson, Christina A. Clarke, Huiyan Ma, Claire Templeman, Dennis Deapen, Leslie Bernstein, Syed A. Aziz.

Abstract: Non-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.

Partial Text: 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 now the fifth most common cancer among US men and women [2]. Although immunodeficiency, autoimmunity, and certain viral infections have been associated with increased risk of some NHLs, the risk factors responsible for the development of most NHLs remain elusive [3], [4]. 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. Case-control [7]–[12] and cohort studies [13]–[16] that have used various menstrual and reproductive characteristics to assess the relationship between endogenous estrogen exposure and NHL risk in women have produced inconsistent results.

The average length of follow-up for women in the analytic cohort was 11 years. The mean ages (±SD) at diagnosis were 69.5±11.6 years (range, 33–93) for all B-cell NHL combined, 69.3±11.7 years (range, 33–92) for diffuse large B-cell lymphoma, 66.3±12.4 years (range, 35–90) for follicular lymphoma, and 72.1±9.7 (range, 48–92) for CLL/SLL.

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 B-cell NHL. Inconsistencies reported in the literature may be the result of combining histologic subtypes which have heterogeneous clinical features and incidence patterns and thus are likely to possess distinct sets of risk factors [5]. Although we observed about a 30% decreased risk of B-cell NHL overall associated with full-term pregnancies, which induces prolonged exposure to increased circulating estrogen levels [25], [26], our study results are not consistent with a major role for endogenous estrogens in the etiology of B-cell NHL. If our hypothesis was correct, we would expect that late age at menarche would increase the risk of B-cell NHL, as a late age at menarche is associated with lower estrogen levels [27], [28]. Instead, later age at menarche was non-significantly associated with reduced risk of B-cell NHL.



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