Introduction: Alcohol-use disorders (AUDs) affect an estimated 283 million people globally, with highest prevalence in the European region (14.8% for men and 3.5% for women) and the Americas (11.5% for men and 5.1% for women), and more common in high-income countries. Hematological malignancies, cancers affecting blood, bone marrow, and lymph nodes, also pose a significant global health burden. While alcohol use is linked to various health risks, its relationship with hematological malignancies is unclear. This systematic review aims to synthesize evidence on the risk of hematological malignancies associated with alcohol use, providing a comprehensive understanding of this relationship and addressing current literature gaps.

Methods: Following the 2020 Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, we systematically searched 6 databases (PubMed, Cochrane Library, Scopus, Web of Science, and EMBASE) on 01/14/24. We searched for studies that met our inclusion criteria to assess the relative risk (RR) of developing hematologic malignancies associated with alcohol consumption. To enable a comprehensive analysis, we categorized hematologic malignancies into five major groups: Lymphoid Neoplasms, Myeloid Neoplasms, Hodgkin Lymphoma (HL), Non-Hodgkin Lymphoma (NHL), and Multiple Myeloma (MM). We registered our study in PROSPERO with the reference CRD42024507139. Meta‐analysis was performed using the R Software to calculate the effect size, presented as logRR with 95% confidence intervals (CI). The random-effects model was used for pooling analysis to compensate for the heterogeneity of the studies. We conducted a risk of bias assessment using the Newcastle-Ottawa Scale to appraise case-control and cohort studies.

Results: A total of 4,659 article records were screened, and 39 studies comprising 13,372,717 participants with hematological malignancies and RR of alcohol consumption were included for analysis. The included studies were distributed across the continents: America (28%), Europe (33%), Asia (31%), and Australia (8%). The overall RR= 0.90 (95% CI: 0.81 to 1.0, I²= 78.6%, p=0.05). The prediction interval extended from 0.50 to 1.63, indicating substantial variability in the study outcomes. In a subgroup analysis, we observed differences based on the type of malignancy. For non-Hodgkin lymphoma (NHL), 17 studies were analyzed, resulting in a relative risk (RR) of 0.85 (95% CI: 0.77 to 0.93, I²= 70.6%). A leave-one-out analysis identified three studies that significantly increased heterogeneity. When these outliers were excluded and the remaining 14 studies were analyzed using a random effects model, the heterogeneity decreased, and the RR narrowed to 0.90 (95% CI: 0.86 to 0.94, I²= 0%). For Myeloid Malignancy, 12 studies were analyzed, indicating an RR= 1.0225 (95% CI: 0.73 to 1.41, p= 0.89, I²= 81.1%). The leave-one-out analysis revealed one study to significantly increase the heterogeneity, an analysis excluding this outlier under the random effects model for the remaining 11 studies showed an RR of 0.92 (95% CI: 0.69 to 1.22, p= 0.59, I²= 75.1%). In the case of Lymphoid Neoplasm, 4 studies estimated an R= 1.17 (95% CI: 0.65 to 2.12, p= 0.58, I²= 77.4%). Regarding MM, 4 studies showed a RR= 0.98, 95% CI: 0.85 to 1.12, p= 0.79, I²= 91.9%). Since there was only one study on HL, it was only included in the overall analysis.

Conclusions: The meta-analysis showed an overall RR= 0.90 (95% CI 0.81-1.00) for hematological malignancies related to alcohol use, suggesting a slight non-statistical significative protective effect. Significant heterogeneity was found in subgroup analyses, indicating variability in effect sizes among different hematological malignancies. Despite the overall high heterogeneity, the NHL subgroup showed a significant protective effect with no observed heterogeneity. However, this result should be interpreted with caution due to methodological limitations and the known health risks of alcohol.

Disclosures

No relevant conflicts of interest to declare.

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2024
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