Alcohol drinking and multiple myeloma risk – a systematic review and meta-analysis of the dose–risk relationship Matteo Rota a,d , Lorenzo Porta d , Claudio Pelucchi d , Eva Negri d , Vincenzo Bagnardi b,e , Rino Bellocco b,f , Giovanni Corrao b , Paolo Boffetta g,h and Carlo La Vecchia d,c The role of alcohol intake in the risk for multiple myeloma (MM) is unclear, although some recent findings suggest an inverse relationship. To summarize the information on the topic, we carried out a systematic review and a dose–risk meta-analysis of published data. Through the literature search until August 2013, we identified 18 studies, eight case–control and 10 cohort studies, carried out in a total of 5694 MM patients. We derived pooled meta-analytic estimates using random-effects models, taking into account the correlation between estimates, and we carried out a dose–risk analysis using a class of nonlinear random-effects meta-regression models. The relative risk for alcohol drinkers versus non/occasional drinkers was 0.97 [95% confidence interval (CI), 0.85–1.10] overall, 0.96 (95% CI, 0.74–1.24) among case–control studies, and 1.00 (95% CI, 0.89–1.13) among cohort studies. Compared with nondrinkers, the pooled relative risks were 0.96 (95% CI, 0.81–1.13) for light (i.e. r 1 drink/day) and 0.89 (95% CI, 0.74–1.07) for moderate-to-heavy (i.e. >1 drink/day) alcohol drinkers. The dose–risk analysis revealed a model- based MM risk reduction of about 15% at two to four drinks/ day (i.e. 25–50 g of ethanol). The present meta-analysis of published data found no strong association between alcohol drinking and MM risk, although a modest favorable effect emerged for moderate-to-heavy alcohol drinkers. European Journal of Cancer Prevention 23:113–121  c 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. European Journal of Cancer Prevention 2014, 23:113–121 Keywords: alcohol drinking, dose–risk relation, meta-analysis, multiple myeloma, systematic review a Department of Health Sciences, Centre of Biostatistics for Clinical Epidemiology, b Department of Statistics and Quantitative Methods, University of Milan-Bicocca, c Department of Clinical Sciences and Community Health, University of Milan, d Department of Epidemiology, IRCCS – Istituto di Ricerche Farmacologiche Mario Negri, e Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy, f Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden, g The Tisch Cancer Institute and Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, USA and h International Prevention Research Institute, Lyon, France Correspondence to Carlo La Vecchia, MD, PhD, Department of Epidemiology, IRCCS – Istituto di Ricerche Farmacologiche Mario Negri, Via G. La Masa 19, 20156 Milan, Italy Tel: + 39 023 901 4527; fax: + 39 023 320 0231; e-mail: carlo.lavecchia@marionegri.it Received 28 October 2013 Accepted 29 October 2013 Introduction Multiple myeloma (MM) is a B-cell plasma neoplasm arising in the bone marrow, characterized by overproduc- tion of light and heavy chain monoclonal immunoglobulin G in serum and/or urine. The pathogenesis of MM is poorly understood. MM usually presents with lytic bone lesions, hypercalcemia, anemia, renal damage, and increased susceptibility to infection (Alexander et al., 2007). In the USA, MM was estimated to account for 1.3 and 1.8% of all cancer diagnoses and deaths, respectively, in 2013 (Siegel et al., 2013). Similarly, in Europe MM accounted for 1.3% of all newly diagnosed cancers in 2012, with an age-standardized rate of 4.5/100 000 individuals (Ferlay et al., 2013). Incidence rates are higher among men than among women, and highest among African Americans. Survival of MM patients is unsatisfac- tory, although the 5-year relative survival rates have risen in American patients, from 26% in patients diagnosed during 1975–1977 to 37% among those diagnosed during 1999–2000 (Baris et al., 2013). Older age, male sex, obesity, exposure to ionizing radiation, and African ancestry are established risk factors for MM; however, little is known about other risk factors (Alexander et al., 2007). Alcohol consumption has been investigated in several studies, with some of them suggesting a favorable effect (Brown et al., 1997; Nieters et al., 2006; Gorini et al., 2007; Hosgood et al., 2007; Chang et al., 2010; Kanda et al., 2010; Gapstur et al., 2012; Kroll et al., 2012) and others providing inconclusive findings (Brown et al., 1992; Monnereau et al., 2008; Allen et al., 2009; Klatsky et al., 2009). A recent report from a cohort study in the Netherlands (Heinen et al., 2013) revealed an increased risk for MM [relative risk (RR) = 1.63, 95% confidence interval (CI), 1.17–2.27] among individuals consuming low doses of ethanol (B10 g/day) compared with abstainers. Conversely, a recent pooled analysis of six case–control studies participating in the ‘International Multiple Myeloma Consortium’ found that ever alcohol drinking was associated with a reduced risk for MM, with pooled RRs of 0.71 (95% CI, 0.58–0.88) for men and 0.82 Review article 113 0959-8278  c 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/CEJ.0000000000000001 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.