No association between cigarette smoking and incidence of plasma cell myeloma: A meta‐analysis of 17 observational studies

Abstract

Plasma cell myeloma (PCM) is a lymphoproliferative disorder characterized by the malignant growth of monoclonal plasma cells within the bone marrow. Although risk factors for the development of PCM have been identified, the etiology on the majority of patients with PCM remains unclear. Cigarette smoking has been postulated as a potential risk factor for lymphoid malignancies; however, the association with PCM is inconclusive. We have carried out a meta-analysis of observational studies to assess the relationship, if any, between cigarette smoking and PCM. A literature search through December 2011 rendered 4 prospective cohort and 13 case-control studies evaluating such association. Our categorical meta-analysis showed that there is no association between ever, current, and former smokers and PCM. This lack of association was maintained when analyzing by study design, study quality, and geographical area of report. Similarly, metaregression analysis showed no association with the number of cigarettes smoked per day. In conclusion, our meta-analysis shows that there is no relationship between cigarette smoking and an increased incidence of PCM. Future studies should focus on other potential risk factors for PCM.PCM is a lymphoproliferative disorder characterized by the malignant accumulation of monoclonal plasma cells within the bone marrow. Patients with PCM can present with anemia, renal dysfunction, hypercalcemia, and bony lytic lesions, and can develop disabling effects from this disease, such as bone fractures or permanent renal insufficiency. In the United States (US) alone, it has been estimated that 21,700 individuals will be diagnosed and 10,710 will die from PCM in 2012 [1]. Despite recent advances in the therapy of PCM (i.e., immunomodulators and proteasome inhibitors), PCM is considered incurable and the majority of patients will ultimately die from PCM-related complications. The etiology of PCM has been an area of active research and few risk factors have been described, such as older age, male sex, African descent, a positive family history, and increased body mass index [2]. However, the large majority of patients diagnosed with PCM do not have an identifiable risk factor. Cigarette smoking has been associated with an increased risk of developing lymphoproliferative disorders [3,4]. The purpose of our study was to evaluate the potential association that cigarette smoking could have on the incidence of PCM by performing a meta-analysis of observational studies.Our literature search through December 2011 rendered 161 returns, from which 133 were excluded because they were case reports, reviews, or did not pertain to our study. The reference list of the remaining 28 studies provided 7 additional studies for a total of 35. From these, 18 were excluded because they did not provide enough data to calculate the outcome, were already included in other studies, or did not focus on PCM or smoking. From these 17 studies, 4 were prospective cohort [5-8] and 13 were case-control studies [9][10][11][12][13][14][1...

A Pooled Analysis of Cigarette Smoking and Risk of Multiple Myeloma from the International Multiple Myeloma Consortium

“…Null associations between smoking and multiple myeloma were also reported in two recent meta-analyses (1, 2), which included two and four studies from our analysis, respectively. Unlike our study, these meta-analyses did not have access to individual-level data, and therefore were limited in their ability to conduct subgroup analyses.…”

“…The etiology of this malignancy remains poorly understood. Past investigations of cigarette smoking and multiple myeloma have generally yielded null results (1, 2), although most studies have been underpowered to detect moderate associations, particularly within population subgroups. To clarify the relationship between cigarette smoking and multiple myeloma, we conducted a pooled analysis of case-control studies participating in the International Multiple Myeloma Consortium (IMMC).…”

Tobacco smoking and risk of multiple myeloma: A meta‐analysis of 40 observational studies

“…From a methodological point of view, this meta‐analysis seems to bear certain assets that need to be discussed. The fact that the present work comprised 40 individual studies, whereas another one on the same topic20 encompassed 17 studies despite a comparable end‐of‐search date, highlights a variety of issues. Strict, meticulous adherence to the MOOSE guidelines,22 thorough contact with the authors for additional data,21 as well as a careful, systematic search in reference lists (“snowball” procedure) resulted in a rather impressive number of studies included.…”

“…In sub‐analyses conducted, neither gender nor smoking status (ever, current, former) differentiated the null association, and the same pattern persisted also for cigars and/or pipes smoking. These results are in agreement with the subset analyses by Castillo et al ., where the various sub‐analyses failed to show any association 20. Also, the absence of a dose‐response relationship, operationalized through duration of smoking, cigarettes smoked per day, pack‐years of smoking, age at onset or years since quit, is another indication that tobacco smoking is not related to plasma cell neoplastic proliferation.…”

“…The biological differences18, 19 between the malignant long‐lived plasma cells of the bone marrow i.e ., the malignant component of MM, and the different B‐cell subpopulations of the lymph nodes that contribute to the development of B‐cell NHLs underlie the separate examination of MM from other B‐cell NHL types. Consequently, a recent meta‐analysis on the effect of cigarette smoking especially on MM was published presenting data from 17 observational studies and pointing to a null association between smoking and MM risk 20. Working independently and in parallel with the aforementioned team, we tried to broaden the number of included studies using a more analytical approach, which encompassed thorough contact with authors21 as well as a broader search algorithm.…”