Abstract

Abstract Background. Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders of hematopoietic stem cells that are characterized by ineffective hematopoiesis, multilineage dysplasia, peripheral cytopenias, and susceptibility to leukemic transformation. Even without progression to leukemia, there is substantial morbidity and mortality. Therefore, a better understanding of the etiology of this disease can lead to a significant reduction in the incidence and the mortality as a consequence, but it remains largely unknown. Smoking and alcohol are important modifiable risk factors for human cancers. However, only a few epidemiological studies have investigated their association with the risk of MDS. Here, we evaluated the association of smoking and alcohol consumption and the risk of MDS in a large-scale population-based cohort study in Japan. Methods. We included 95,950 Japanese subjects (45,451 men and 50,059 women; age 40-69 years at baseline) of the Japan Public Health Center-based Prospective Study who completed a questionnaire about their smoking and alcohol habits. During 18.3 years of follow-up, we identified 70 MDS cases (50 men and 20 women). We calculated hazard ratios (HRs) and their 95% confidence intervals (95% CI) using the Cox proportional hazards model to describe the relative risk of MDS associated with the smoking categories at baseline (never smokers, former smokers, current smokers, ever smokers of <30 and ≥30 pack-years) and the drinking categories at baseline (non-drinkers, occasional drinkers, and regular drinkers of 1-299 or ≥300 g/week of ethanol) after adjustment for potential confounders. Results. Smoking was marginally associated with an increased risk of MDS among men, with a HR for current smokers relative to never smokers of 2.11 (95% CI: 0.91-4.89). This risk increase was also observed in ever smokers with more than 30 pack-years compared to never smokers (HR=2.22, 0.95-5.19). A linear increase in HR with increasing pack-years was also seen, albeit without statistical significance (p-trend=0.083). In contrast, alcohol consumption was associated with a dose-dependent decrease in the risk of MDS among men (nondrinkers: reference, occasional drinkers: HR=0.48, 0.16-1.43; 0-299 g/week: HR=0.37, 0.19-0.74; ≥300 g/week: HR=0.45, 0.20-0.99, p for trend=0.008). All types of alcohol beverages (sake, distilled spirit and beer) consistently showed a protective effect. We also explored a possible interaction between smoking and alcohol consumption, but no obvious interaction was observed. Conclusions. This study showed that alcohol has a significant protective effect on the risk of MDS among Japanese men. In addition, this study also provides evidence that smoking increases the risk of MDS among Asian population, as it does among Western populations. Previous findings on the association between alcohol and the risk of MDS have been inconsistent, and further investigation across multiple populations is needed. Citation Format: Tomotaka Ugai, Keitaro Matsuo, Norie Sawada, Motoki Iwasaki, Taiki Yamaji, Taichi Shimazu, Shizuka Sasazuki, Manami Inoue, Yoshinobu Kanda, Shoichiro Tsugane. Smoking and alcohol and the risk of myelodysplastic syndrome: The JPHC study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2282. doi:10.1158/1538-7445.AM2017-2282

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