Chloroform Exposure and Risk of Leukemia: Systematic Review and Meta-analysis

Yaser Soleimani^1*Sheyda Mahmoudi¹Mahdi Daraei¹Ali Aryanejad¹Ali Hosseini Sani¹Alireza Khazali¹Soroush Khorsand¹Mohammadreza Mahdavi¹Setareh Sabeti¹Hamid Sadeghi¹Mohammad Javad Shahsavari¹Mahdieh Varseh²Saeideh Karamian¹Seyed Alireza Mosavi-Jarrahi³Mohammad Reza Taherian⁴Goljamal Jorjani⁴

• ¹Shahid Beheshti University of Medical Sciences, Tehran, Iran
• ²Khomein University of Medical Sciences, khomein, Iran
• ³Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Alborz, Iran
• ⁴Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Alborz, Iran

The aim of this systematic review and meta-analysis was to evaluate the association between chloroform exposure and the risk of leukemia, quantify the overall risk, and identify potential sources of heterogeneity among different leukemia subtypes. Methods: A comprehensive literature search was conducted across PubMed, Web of Science, and Scopus to identify relevant epidemiological studies published up to December 2023. Inclusion criteria focused on human studies that assessed chloroform exposure and reported leukemia incidence or mortality. Data were extracted and analyzed using randomeffects models to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I², τ², and Cochran's Q test. Publication bias was evaluated using Begg's test. Results: Four case-control studies were included, spanning publication years from 2001 to 2023, with sample sizes ranging from 67 to 31,292 participants. The overall pooled OR for the association between chloroform exposure and leukemia was 0.75 (95% CI: 0.25-2.27), indicating no statistically significant association. However, substantial heterogeneity was observed (I² = 95%). Begg's test showed no significant publication bias (p = 1.0000). Conclusion: This systematic review and meta-analysis did not find a significant overall association between chloroform exposure and leukemia risk. The significant association observed for AML suggests that chloroform exposure might increase the risk of this specific subtype, while the reduced risk for CLL warrants further investigation. The high heterogeneity underscores the need for standardized methodologies and further research to clarify these associations, particularly focusing on different leukemia subtypes, exposure levels, and population characteristics. These findings can inform public health policies and targeted prevention strategies to mitigate potential risks associated with chloroform exposure.