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

Abstract

This meta-analysis aims to quantitatively synthesize all available data on the association between tobacco smoking and multiple myeloma (MM) risk. Eligible studies were identified and pooled effect estimates (odds ratios and relative risks) were calculated regarding ever, current and former smoking. Separate analyses were performed on case-control and cohort studies, as well as on males and females. Meta-regression analysis with percentage of males, mean age, years of smoking, pack-years, cigarettes per day, years since quit and age at onset was performed. Forty articles were deemed eligible; of them 27 used a case-control design (4,625 cases and 21,591 controls) and 13 used a cohort design (2,228 incident cases among a total cohort size equal to 1,852,763 subjects). Ever smoking was not associated with MM risk (pooled effect estimate 5 0.92, 95% confidence interval (CI): 0.85-1.00); similar results were obtained for current (pooled effect estimate 5 0.87, 95% CI: 0.74-1.03) and former smoking (pooled effect estimate 5 1.04, 95% CI: 0.96-1.13). Regarding ever smoking, the null association was reproducible upon cohort studies (pooled effect estimate 5 1.01, 95%CI: 0.89-1.15), whereas the inverse association in case-control studies (pooled effect estimate 5 0.87, 95% CI: 0.78-0.96) was particularly due to the bias-prone hospital-based ones. Meta-regression analysis did not yield statistically significant results. In conclusion, MM does not seem to be associated with tobacco smoking. There is a need to further explore how molecular mechanisms are involved in the resistance of MM progenitor cells toward smoking.Multiple myeloma (MM) (plasma cell myeloma, myelomatosis and Kahler's disease) is a mature B-cell neoplastic proliferation, 1 characterized by bone marrow plasmacytosis and overproduction of monoclonal immunoglobulin. This disease is associated with anemia, hypercalcemia, skeletal pain and lytic bone lesions, renal insufficiency, among other related organ or tissue impairment. 2 MM constitutes 10-20% of all hematologic malignancies; its prevalence is expected to rise in Western countries due to the population aging, with 30% of the patients aged more than 75 years. 3 It is estimated that in the US, during 2012, 12,190 men and 9,510 women will be diagnosed and 10,710 men and women will die of myeloma, with a 5-year relative survival of 41%. 4 MM cause remains unclear; there is convincing literature for risk factors, such as increased age, positive family history, male gender and black race, 5 while monoclonal gammopathy of undetermined significance (MGUS) consistently precedes MM. 6 Familial clustering of the disease also suggests a genetic background. 5 Multiple etiologies have been suggested, such as exposure to benzene, petroleum products and to ionizing radiation, as well as agricultural or industrial occupation; on the other hand, conventional cancer causes such as tobacco smoking, obesity and dietary characteristics are probably less implicated. 7,8 Tobacco smoking is among the leading preventable causes...

Risk Factors for Multiple Myeloma: A Systematic Review of Meta-Analyses

“…67 Regarding the spectrum of lifestyle parameters, both overweight and obesity correlated with increased MM incidence and mortality 51 ; the underlying explanations may involve modified IGF-1, 68 adiponectin, 69 inflammatory cytokine 70 levels, or adipocyteebone marrow cell interactions. 71 On the other hand, smoking 42 and physical activity 36 were not significantly associated with MM risk. The potential protective effects of alcohol consumption on MM risk 61 have been attributed to its immunomodulatory effects [72][73][74] or its inhibition through ethanol on the mammalian target of rapamycin signaling.…”

“…51 On the other hand, the inverse association between physical activity and MM risk did not reach statistical significance 36 ; similarly, no significant association implicated ever or current smoking. 42 An overall protective association was noted with respect to ever alcohol consumption, which was particularly evident at the assessment of wine intake and in the subpopulation of women. 61 …”

Physical Activity in Relation to Risk of Hematologic Cancers: A Systematic Review and Meta-analysis

“…Although the relations of physical activity to hematologic cancer subtypes did not vary according to smoking, in a subanalysis of total hematologic cancer, we found that studies that adjusted for smoking showed a stronger inverse association with physical activity than studies that did not adjust for smoking. Smoking is inversely related to physical activity (55) and positively associated with all investigated hematologic cancer subtypes (56-58) except multiple myeloma (59). Thus, adjustment for smoking would be expected to produce a less pronounced inverse association between physical activity and total hematologic cancer than not adjusting for smoking.…”

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

“…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).…”