Association of the selenoprotein 15-kDa (SEP15) polymorphisms with cancer risk: a meta-analysis

Selenoproteins are involved in antioxidant defense, the redox signaling pathway and cell homeostasis. Primary studies have shown that single-nucleotide polymorphisms in the selenoprotein gene (SEP15) are associated with cancer risk. However, conflicting outcomes warrant a meta-analysis to obtain more precise estimates. Literature search yielded 18 case-control studies from 12 articles. We calculated pooled odds ratios (OR) and 95% confidence intervals (CI) of twoSEP15polymorphisms (rs5845 and rs5859) using standard genetic models (homozygous, recessive, dominant and codominant). Subgroup analysis was based on statistical power (80% cutoff) and cancer type (breast/respiratory/genitourinary/colorectal). Heterogeneity of the outcomes necessitated examining their sources (outlier treatment). Multiple comparison outcomes were corrected with the False Discovery Rate (P-aF). Our core findings lay in the post-outlier recessive subgroup outcomes, where risks in the powered study (>= 80%) was increased (OR 1.26, 95% CI 1.02-1.57,P-aF = 0.047) while that in genitourinary cancer was protective (OR 0.29, 95% CI 0.20-0.43,P-aF< 10(-4)). The potency of outlier treatment in unmasking significant associations and generating homogeneity provides good evidence ofSEP15's role in cancer. In the clinical sense, selenium chemo-intervention may be of benefit among persons with particularSEP15genotypes.