Risk of Multiple Myeloma following Medication Use and Medical Conditions: A Case-Control Study in Connecticut Women

Landgren, Ola; Zhang, Yawei; Zahm, Sheila Hoar; Inskip, Peter D.; Zheng, Tongzhang; Baris, Dalsu

doi:10.1158/1055-9965.epi-06-0097

Cited by 53 publications

(63 citation statements)

References 58 publications

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“…This effect was specifically pronounced in the late intervention period, suggesting transient suppression of precursor progression to PCN 35 during the course of treatment. Substantially reduced risks of multiple myeloma or PCN associated with menopausal hormone use have also been reported in case-control studies from Italy (OR 5 0.2, 95% CI 0.1-1.0) 36 and Connecticut (OR 5 0.6, 95% CI 0.4-0.99) 21 as well as by a prospective cohort study in the US for estrogen only users (RR 5 0.63, 95% CI 0.29-1.37). To our knowledge, this is the first study to examine associations among CEE alone and CEE plus MPA use and NHL incidence in a randomized clinical trial setting.…”

Section: Discussionmentioning

confidence: 64%

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

Kato

Chlebowski

Hou

et al. 2015

Intl Journal of Cancer

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Estrogens are important immunomodulators, exerting significant effects on cell proliferation, apoptosis, cytokine production and differentiation of hematopoietic cells. Estrogen receptors are expressed on normal B and T lymphocytes, bone marrow and in leukemia and lymphoma cell lines. Epidemiologic evidence for the association of menopausal hormone use with risk of non-Hodgkin's lymphoma (NHL) has been mixed; however, all of the investigations have been observational. We analyzed the data from Women's Health Initiative hormone therapy trials where conjugated equine estrogens (CEE; 0.625 mg/d) plus medroxyprogesterone acetate (MPA; 2.5 mg/d) (n 5 16,654) or CEE alone (women with prior hysterectomy) (n 5 10,685) were tested against placebos and the intervention lasted a median of 5.6 years in the CEE 1 MPA trial and 7.2 years in the CEE alone trial. During 13 years of follow-up through September 20, 2013 383 incident NHL cases were identified. We used the intent-to-treat approach to calculate incidence rates of NHL, hazards ratios (HR) and 95% confidence intervals (CI) by treatment group. Incidence of NHL was virtually the same in the treatment and placebo groups. The HR was 1.02 (95%CI 0.74-1.39) for CEE alone, 0.98 (95% CI 0.76-1.28) for CEE1MPA, and 1.00 (95% CI 0.82-1.22) for both combined. There were no specific NHL subtypes associated with either type of the treatment, except a marginally decreased risk of plasma cell neoplasms (HR5 0.53 95% CI 0.27-1.03) in the CEE-alone group. These results do not support a role of estrogen alone or combined with progestin in the development of NHL among postmenopausal women.Lymphoid neoplasms, including lymphoma, myeloma and lymphocytic leukemia, comprise the 5th most commonly diagnosed cancer in the United States, 1 following breast, prostate, lung and colorectal cancers. Although lymphoid neoplasms are clinically and etiologically heterogeneous, to a large extent, severe disruption of immune function has been

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Section: Discussionmentioning

confidence: 64%

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

Kato

Chlebowski

Hou

et al. 2015

Intl Journal of Cancer

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“…30 Moreover, a recent case-control study found a statistically significant 3.1-fold increased risk of multiple myeloma among women who had been treated with insulin. 31 Elevated insulin concentrations can lead to an increase in the concentrations of bioavailable insulin-like growth factor-I (IGF-I), which is involved in the hematopoietic process for both normal and malignant cells. 32 IGF-I has been shown to promote myeloma cell proliferation 33 independent of IL-6.…”

Section: Discussionmentioning

confidence: 99%

Body mass index and risk of multiple myeloma: A meta‐analysis

Larsson

Wolk

2007

Intl Journal of Cancer

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Excess body weight has been identified as a risk factor for a variety of cancer types. However, whether excess body weight increases the risk of multiple myeloma remains controversial. We conducted a meta-analysis to quantitatively summarize the evidence from epidemiologic studies of the associations of overweight and obesity with the risk of multiple myeloma. We searched the MEDLINE and EMBASE databases (1966 to May 2007) and the reference lists of retrieved articles. Cohort and case-control studies were included if they reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the relation between body mass index and multiple myeloma incidence or mortality. A random-effects model was used to combine study-specific results. A total of 11 cohort studies (involving 13,120 cases) and 4 case-control studies (1,166 cases and 8,247 controls) were included in the meta-analysis. Compared with individuals with normal weight, the risk of multiple myeloma was statistically significantly higher among those who were overweight (cohort studies: RR, 1.12, 95% CI, 1. Key words: body mass index; meta-analysis; multiple myeloma; obesity; review Multiple myeloma is a neoplasm of plasma cells of B lymphocyte origin. The prognosis of multiple myeloma is poor; only about one third of patients survive 5 or more years and 16% survive 10 years.1 Therefore, identification of risk factors amenable for modification could have marked impact on reducing morbidity and mortality from the disease. Little is known about the etiology of multiple myeloma. Suspected risk factors include chronic immune stimulation, autoimmune disorders, exposure to ionizing radiation, occupational exposure to pesticides or herbicides and prolonged use of hair dyes. 2Excess body weight has been recognized as a risk factor for a variety of malignancies, including cancer of the colon, breast (in postmenopausal women), endometrium, kidney, and esophagus (adenomcarcinoma).3 Overweight and obesity may also increase the risk of multiple myeloma, but findings from epidemiologic studies have been inconsistent. We therefore undertook a metaanalysis of cohort and case-control studies to quantitatively assess the associations of overweight and obesity, defined by body mass index (BMI), with risk of multiple myeloma. Material and methods Study selectionWe searched the electronic databases MEDLINE and EMBASE for studies on BMI and risk of multiple myeloma that were published from 1966 to May 2007, using the key words body mass index, BMI or obesity combined with myeloma or hematopoietic cancer. Furthermore, we reviewed the reference lists of retrieved articles to search for more studies. No language restrictions were imposed.To be included in our meta-analysis, a published study had to fulfill the following criteria: (i) cohort or case-control study in which multiple myeloma incidence or mortality was an outcome; and (ii) report relative risk (RR) estimates (odds ratios in casecontrol studies) with corresponding 95% confidence intervals (CIs) (or information...

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“…Familial aggregation of autoimmune disorders in both patients with MGUS and multiple myeloma have been observed suggesting a common underlying genetic mechanism (15)(16)(17). In addition, medications used in the treatment of autoimmune disorders such as steroids, insulin, and immunomodulators have been associated with a heightened risk of malignancy (18).…”

Section: Introductionmentioning

confidence: 99%

“…Several observational studies have been conducted investigating the hypothesis of sustained or chronic antigenic stimulation and the development of multiple myeloma and most recently MGUS, but findings have been inconsistent and have largely been hindered by the rarity and heterogeneity of the autoimmune disorders investigated (15,17,19,18,20,21). We therefore, sought to perform an extensive systematic review of the published literature to evaluate the strength of the evidence linking prior autoimmune disease and risk of MGUS and multiple myeloma.…”

Section: Introductionmentioning

confidence: 99%

Prior Autoimmune Disease and Risk of Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma: A Systematic Review

McShane

Murray

Landgren

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Several observational studies have investigated autoimmune disease and subsequent risk of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. Findings have been largely inconsistent and hindered by the rarity and heterogeneity of the autoimmune disorders investigated. A systematic review of the literature was undertaken to evaluate the strength of the evidence linking prior autoimmune disease and risk of MGUS/multiple myeloma.Methods: A broad search strategy using key terms for MGUS, multiple myeloma, and 50 autoimmune diseases was used to search four electronic databases (PubMed, Medline, Embase, and Web of Science) from inception through November 2011.Results: A total of 52 studies met the inclusion criteria, of which 32 were suitably comparable to perform a meta-analysis. "Any autoimmune disorder" was associated with an increased risk of both MGUS [n ¼ 760 patients; pooled relative risk (RR) 1.42; 95% confidence interval (CI), 1.14-1.75] and multiple myeloma (n>2,530 patients; RR 1.13, 95% CI, 1.04-1.22). This risk was disease dependent with only pernicious anemia showing an increased risk of both MGUS (RR 1.67; 95% CI, 1.21-2.31) and multiple myeloma (RR 1.50; 95% CI, 1.25-1.80).Conclusions: Our findings, based on the largest number of autoimmune disorders and patients with MGUS/multiple myeloma reported to date, suggest that autoimmune diseases and/or their treatment may be important in the etiology of MGUS/multiple myeloma. The strong associations observed for pernicious anemia suggest that anemia seen in plasma cell dyscrasias may be of autoimmune origin.Impact: Underlying mechanisms of autoimmune diseases, general immune dysfunction, and/or treatment of autoimmune diseases may be important in the pathogenesis of MGUS/multiple myeloma. Cancer Epidemiol Biomarkers Prev; 23(2); 332-42. Ó2014 AACR.

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Risk of Multiple Myeloma following Medication Use and Medical Conditions: A Case-Control Study in Connecticut Women

Cited by 53 publications

References 58 publications

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

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

Body mass index and risk of multiple myeloma: A meta‐analysis

Prior Autoimmune Disease and Risk of Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma: A Systematic Review

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