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

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][15][16][17][18][19][20][21].The prospective studies were published between 1990 and 2007, and included 1,232 cases identified in a total cohort of 789,000 individuals.Three studies were from the US and 1 from Europe.Two studies were of high quality and two were considered intermediate.The case-control studies were published between 1987 and 2008, and included 4,484 cases and 19,810 controls.Six studies were from the US, six from Europe, and one from Asia.Eight studies were considered of intermediate quality and five of high quality.There was no statistical association between cigarette smoking and incidence of PCM identified in ever smokers, former smokers, or current smokers (Table I).Forests plots are shown in Fig. 1.Similarly, when evaluating subset analyses by study design, study quality, or geographic region, no statistical association was found (Table I).Data were insufficient to perform meta-analysis by sex.Meta-regression analyses evaluating the number of cigarettes smoked per day showed no linear association with incidence of PCM (data not shown).Data were insufficient to perform meta-regression analyses on duration (years) or cumulative smoking (pack-years).Based on the results of our study, cigarette smoking does not appear to increase the incidence of PCM.Subset analyses by study design and geo-

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