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

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.

Inverse association between soy intake and non-Hodgkin lymphoma risk among women: a case–control study in Japan

“…One recent study found a positive association between reproductive factors and the risk of NHL, but others reported no association [43][44][45]. Although these proposed factors were not validated in our study, we found a difference in age at menarche between cases and controls, albeit without statistical significance.…”

Gender Aspects in Extranodal Marginal Zone B-Cell Lymphoma of the Mucosa-Associated Lymphoid Tissue: Does Sex Matter?

“…With a 30% lower incidence rate for women, male gender per se may be considered a risk factor [5,27]. It has been postulated that this is mostly based on the influence of sex hormones (and particularly estrogen) on the immune system [27,28]. Consequently, also pregnancy and live births were shown to be protective factors with a risk reduction of 0.84 (95% CI 0.68-1.04) [28].…”

“…It has been postulated that this is mostly based on the influence of sex hormones (and particularly estrogen) on the immune system [27,28]. Consequently, also pregnancy and live births were shown to be protective factors with a risk reduction of 0.84 (95% CI 0.68-1.04) [28]. Interestingly, and in line with the fact that clinical behavior and prognosis significantly differ between lymphoma subsets, SEER data have demonstrated that though men are more likely to suffer from NHL in general, some entities are evenly distributed or even more likely to arise in women including follicular lymphoma and marginal zone lymphoma [5].…”

Menopausal estrogen therapy and non‐Hodgkin's lymphoma: A post‐hoc analysis of women's health initiative randomized clinical trial

“…For most of these factors, associations have been observed in both directions, and significantly increased or decreased risks of NHL from one study were not replicated by others. 15,[17][18][19][31][32][33] The only exception is an inverse association between parity and NHL, which was reported by more than two studies. 23 As far as the associations with menopausal hormone use in observational studies are concerned, case-control studies have generally reported decreased risks of NHL among menopausal hormone users, yielding a pooled odd ratio (OR) of 0.70 (95% CI 0.54-0.90) in an international pooled analysis, InterLymph.…”