Influence of Lysyl oxidase Polymorphisms in Cancer Risk: An Updated Meta-analysis

Background: The aim of this study was to investigate associations between polymorphisms in the Lysyl oxidase (LOX) gene with susceptibility to cancer. The role of LOX in carcinogenesis prompted several association studies in various cancer types; however the outcomes of these studies have inconsistent. Thus, we performed a meta-analysis to obtain more precise estimates. Materials and Methods: A literature search yielded 14 articles from which we examined five cancer groups: breast, bone, lung, gastrointestinal, and gynecological cancers. For each cancer group, pooled odds ratios (ORs) and confidence intervals (95% CIs) were calculated using standard genetic models. High significance (p-value for association [p(a)] < 0.00001), homogeneity (I-2 = 0%), and high precision of effects (CI difference [CID] <1.0 [upper CI - lower CI]) comprised the three criteria for strength of evidence. We used sensitivity analysis to assess robustness of the outcomes. Results: We generated 28 comparisons from which 13 were significant (p(a) < 0.05), indicating increased risk, (OR >1.00) found in all cancer groups except breast (p(a) = 0.10-0.91). Of the 13, three met all criteria (core) for strength of evidence (p(a) < 0.00001, CIDs 0.49-0.56 and I-2 = 0%), found in dominant/codominant models of gynecological cancers (ORs 1.52-1.62, 95% CIs 1.26-1.88) and codominant model of lung cancer (OR 1.44, 95% CI 1.19-1.74). These three were deemed robust. Conclusion: Based on the three core outcomes, associations of LOX 473G/A with lung, ovarian, and cervical cancers indicate 1.4-1.6-fold increased risks, underpinned by robustness and high statistical power at the aggregate level.