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Hormone Replacement Therapy and Risk of Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia¹

Departments of Health Sciences Research [J. R. C., C. M. V., C. A. J., T. A. S.], Hematology [T. M. H. S. M. A., T. E. W.], and Laboratory Medicine and Pathology [P. J. K.], Mayo Clinic, Rochester, Minnesota 55905; Department of Health Services Research, Vanderbilt University Medical Center, Nashville, Tennessee 37232 [W. Z.]; Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104 [J. D. P.]; and Division of Epidemiology, University of Minnesota School of Public Health, Minneapolis, Minnesota 55454 [A. R. F.]

Our objective in this study was to evaluate whether the useof hormone replacement therapy (HRT) is associated with non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL). A cohort of 37,220 Iowa women ages 55 to 69 years in 1986 with no history of prior cancer was linked annually to a population-based cancer registry. Through 1998 (13 years of follow-up), 258 incident cases of NHL were identified, including 135 cases of diffuse NHL, 58 cases of follicular NHL, and 31 cases of small lymphocytic NHL. In addition, 63 cases of CLL were identified. Current and former use of HRT (primarily estrogen) and other cancer risk factors were self-reported on the baseline (1986) questionnaire. Compared with never users of HRT at study baseline, current [multivariate relative risk (RR), 1.4; 95% confidence intervals (CIs), 0.9–2.0) but not former (RR, 1.1; 95% CI, 0.8–1.4) users were at increased risk of NHL after adjustment for age and other confounding factors. This association was seen only in nodal NHL [RR_current, 1.5 (95% CI, 1.0–2.4); RR_former, 1.1 (95% CI, 0.8–1.6)] and was not apparent for extra-nodal sites. Of the common subtypes, there was a strong positive association with follicular NHL [RR_current, 3.3 (95% CI, 1.6–6.9); RR_former, 2.6 (95% CI, 1.4–4.7)], and women who were current users for more than 5 years had the highest risk (RR, 3.9; 95% CI, 1.8–8.6). There was no association with diffuse or small lymphocytic NHL, or with CLL. Most of the follicular NHLs were nodal (88%), and exclusion of extra-nodal sites slightly strengthened the association with HRT. For diffuse NHL, 64% of the cases were nodal, and there was no association of HRT with either nodal or extra-nodal sites. These data suggest that HRT is a risk factor for follicular NHL but not for diffuse or small lymphocyte NHL or CLL.

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