Benzene exposure and lung cancer risk: a systematic review and meta-analysis of human studies

Background Lung cancer is the second most commonly diagnosed cancer, with more than 2.2 million new cases and nearly 1.8 million deaths estimated worldwide in 2020. Although benzene is classified as human carcinogen (Group 1) on the base of its association with acute myeloid/non-lymphocytic leukaemia, there is “limited evidence that benzene cause lung cancer”. The aim of this study is to examine the potential link between benzene exposure and risk of lung cancer in humans by a systematic review of epidemiological studies and meta-analysis. Methods We carried out a comprehensive literature search until 22 January 2022 through PubMed, Web of Science and Scopus database to identify all articles on the association between benzene exposure and lung cancer incidence and/or mortality. Studies reporting lung cancer risk without identifying specifically the exposure to benzene, or that considered many different solvent together, were excluded. We extracted the risk both as lung cancer incidence and mortality estimate of the highest and the lowest reported categories of benzene exposure from each study and conducted a meta-analysis using a random-effects model. Results Twenty observational studies were included in the meta-analysis, of which six carried out in USA, 4 in Canada and China, 2 in Korea, and one each in UK, Iran, Italy and France. Half of the studies were performed in men only (n = 10), three studies considered both males and females separately, and seven studies reported the data combined. The incidence of lung cancer was considered in 10 studies, the mortality in eight studies, while two studies reported both incidence and mortality. Fourteen studies considered the occupational benzene exposure, four the residential exposure and two studies evaluated the benzene exposure by a biomarker (urinary level of S-phenyl mercapturic acid). Pulling together all data, we obtained a 17% increase of lung cancer risk in association with benzene exposure (RR = 1.17; 95% CI: 1.05-1.29). Selecting the studies which adjusted the data for smoking (n = 9) the risk increase to 32% (RR = 1.32; 95% CI: 1.06-1.65). Considering separately, the incidence risk was 1.21 (95% CI: 1.03-1.42) while the mortality risk was 1.13 (95% CI: 0.98-1.31). No evidence of publication bias have been detected. Conclusions Benzene can be an important risk factor for lung cancer. However, to obtain more reliable data on the extent of lung cancer risk as a function of the benzene exposure dose, further studies are needed.