ABSTRACT: Numerous studies have focused on the association between heme oxygenase-1 (HO-1) gene promoter polymorphisms and susceptibility to cancer; however, results remain ambiguous. The present systematic Human Genome Epidemiology review and meta-analysis aimed to clarify this association. A systematic search was used to assess the association of HO-1 gene polymorphisms with cancer susceptibility in the PubMed, Web of Science, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure databases, with all reviewed studies published before April 10, 2017. Review Manager 5.3 and Stata 12.0 software were used to perform the meta-analysis. A total of 14 studies were included in the analysis. Overall, no significant associations of the HO-1 (GT)n and T(-413)A polymorphisms with cancer susceptibility were identified. However, subgroup analyses by ethnicity and cancer type indicated that the LL and L-allele (LL+LS) genotypes of HO-1 (GT)n were associated with increased susceptibility to cancer compared with the SS+SL and SS genotypes in the following subgroups: East Asian [LL+LS vs. SS: odds ratio (OR)=1.51, 95% confidence interval (CI)=1.11-2.05, P=0.0003; LL vs. SS+SL: OR=1.44, 95% CI=1.04-2.01, P=0.03; LL vs. SS: OR=1.64, 95% CI=1.07-2.52, P=0.02]; squamous cell carcinoma (LL+LS vs. SS: OR=1.78, 95% CI=1.35-2.34, P<0.05; LL vs. SS+SL: OR=1.71, 95% CI=1.34-2.18, P<0.05; LL vs. SS: OR=2.26, 95% CI =1.62-3.14, P<0.05); and digestive tract cancer + East Asian (LL+LS vs. SS: OR=1.56, 95% CI=1.22-1.98, P<0.05; LL vs. SS: OR=1.80, 95% CI=1.06-3.05, P<0.05). These findings indicated that there was no association of the HO-1 (GT)n and T(-413)A polymorphisms with cancer susceptibility, while the L-allele genotypes (LL and LS) of HO-1 (GT)n may be susceptibility factors for cancer in East Asian, digestive tract cancer in East Asian and squamous cell carcinoma populations. Due to limitations of the reviewed studies, additional large-scale and refined studies are now required to confirm the present findings.
