Cigarette Smoking and the Risk of Adult Myeloid Disease: A Meta-Analysis

Abstract

Background: The adult myeloid diseases, myelodysplastic syndrome and acute myeloid leukemia, have been reported to be associated with cigarette smoking, but the results have been conflicting. Previous studies may have ignored the relationship between myelodysplastic syndrome and acute myeloid leukemia, where approximately one-third of myelodysplastic syndrome cases will progress to acute myeloid leukemia, which could induce a serious bias in independent analyses. For the purposes of researching pathogenesis, we suggest that myelodysplastic syndrome and acute myeloid leukemia should be regarded as a single class of adult myeloid disease, and herein assessed the relationship between cigarette smoking and the risk of adult myeloid disease.

Methods: The PubMed, Cochrane Library, EBSCO, and EMBASE databases were systematically searched for reports published from 1990 to 2015. Two authors independently assessed the methodological quality and the extracted data. The odds ratios and adjusted odds ratios (OR), a sensitivity analysis, and the publication bias were analyzed using the CMA v2 (Comprehensive Meta Analysis Version 2) software program.

Results: Twenty-five studies were included in this meta-analysis. The publication dates ranged from 1990 to 2014. The pooled OR in current smokers and ever-smokers showed an increased risk of adult myeloid disease, with ORs of 1.45 (95% CI, 1.30-1.62; p<0.001) and 1.23 (95% CI 1.15-1.32; p<0.001) versus non-smokers, respectively. In the subset analyses, the OR of adult myeloid disease was increased regardless of the form of disease, geographical region, NOS (Newcastle Ottawa Scale) score, and source of controls. The smoking status was divided into <20 and ≥20 cigarettes per day, and these groups had ORs of developing adult myeloid disease of 1.24 (95% CI, 1.09-1.40; p = 0.001) and 1.32 (95% CI, 1.14-1.53; p<0.001), respectively. In the groups divided based on the number of years the subjects had smoked (<20 and ≥20 years), the ORs were 1.05 (95% CI, 0.90-1.23; p = 0.25) and 1.30 (95% CI, 1.16-1.45; p<0.001), respectively. Similarly, <20 and ≥20 pack-years were associated with ORs of 1.15 (95% CI, 1.03-1.29; p = 0.017) and 1.34 (95% CI, 1.18-1.52; p<0.001), respectively.

Conclusions: This meta-analysis, for the first time, combined myelodysplastic syndrome with acute myeloid leukemia to assess the overall risk of adult myeloid disease, and it demonstrated that cigarette smoking is associated with a significantly increased risk of adult myeloid disease.

Fig 1. A flowchart of the study selection process.

Fig 2. The odds ratio estimates of the risk of developing adult myeloid disease in smokers.

(A) A forest plot of the risk of developing adult myeloid disease in current smokers. (B) Duval and Tweedie’s trim-and-fill funnel plots were used to observe and adjust the publication bias in current smokers. (C) A forest plot of the risk of developing adult myeloid disease in ever-smokers. (D) Duval and Tweedie’s trim-and-fill funnel plots were used to observe and adjust the publication bias in ever-smokers. Among Fig B and D, The white circles represent observed studies, and black circles represent possibly missed studies imputed using Duval and Tweedie’s trim-and-fill method. White and black rhombuses represent observed and theoretical combined effect size, respectively.

Fig 3. Forest plots of the risk of adult myeloid disease in current smokers.

(A) Forms of disease, (B) geographical region, (C) NOS score (high and medium quality), (D) source of controls.

Fig 4. Forest plots of the risk of adult myeloid disease in ever-smokers.

(A) Forms of disease, (B) geographical region, (C) NOS score (high and medium quality), (D) source of controls.

Fig 5. Forest plots of the association of adult myeloid disease with the smoking status based on cigarettes smoked per day (A-B), the duration of smoking (in years) (C-D), and the pack-years smoked (E-F).