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 two SEP15 polymorphisms (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 (PaF). 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, PaF = 0.047) while that in genitourinary cancer was protective (OR 0.29, 95% CI 0.20-0.43, PaF < 10-4). The potency of outlier treatment in unmasking significant associations and generating homogeneity provides good evidence of SEP15's role in cancer. In the clinical sense, selenium chemo-intervention may be of benefit among persons with particular SEP15 genotypes.AbbreviationsAnumber of unduplicated articles that contributed to instabilityAManalysis modelBnumber of robust comparisonsBCbreast cancerBLCbladder cancercDNAcomplementary deoxyribonucleic acidCIconfidence intervalCIDconfidence interval differenceCRCcolorectal cancerDdecreased riskEHeliminated heterogeneityFfixed-effectsFDRFalse Discovery RateGUCgenitourinary cancersGSgained significanceHBhospital-basedHWEHardy-Weinberg EquilibriumIincreased riskI2measure of heterogeneitykDakiloDaltonLAClaryngeal cancerLUClung cancermafminor allele frequencynnumber of studiesNnumber of comparisonsNMnot mentionedNOSNewcastle-Ottawa ScaleORodds ratioPaP value for associationPaδP value for association (pre-FDR)PaFP value for association FDR-correctedPbP value for heterogeneityPBpopulation-basedPCprostate cancerPRISMAPreferred Reporting Items for Systematic Reviews and Meta-AnalysesPROpre-outlierPSOpost-outlierRrandom-effects[R]referenceRCrespiratory cancersRNSretained non-significanceROSreactive oxygen speciesSEPselenoproteinsSEP15selenoprotein geneSNPsingle nucleotide polymorphismSWShapiro-Wilk testUSAUnited States of Americavvvariantwvheterozygouswwwild-type.

PROGINS Polymorphism of the Progesterone Receptor Gene and the Susceptibility to Uterine Leiomyomas: A Systematic Review and Meta-Analysis.

AIMS: Steroid hormones play a central role in modulating the growth of uterine leiomyoma, and several studies have suggested that polymorphisms in genes encoding these hormones and their receptors may be risk factors for developing the disease. Progesterone is a potent antagonist of estrogen-induced proliferation in the endometrium, and the PROGINS polymorphisms have been associated with leiomyoma, but the results are inconsistent. In this study, we aimed to investigate the possible associations between the PROGINS polymorphisms and uterine leiomyoma. MATERIALS AND METHODS: MEDLINE using PubMed, Science Direct, and Google Scholar databases was searched using the terms "PROGINS," "progesterone receptor," "polymorphism," and "leiomyoma." We estimated risk with odds ratios [ORs] and 95% confidence intervals using standard genetic models (homozygous, recessive, dominant, and codominant). RESULTS: Six studies were included in this meta-analysis based on 837 cases and 1011 controls. Subjects in three studies were Asian (365 cases/391 controls), and five were non-Asian (472 cases/620 controls). Our findings showed no association between PROGINS and leiomyoma in the overall analysis (OR 0.91-1.07, p = 0.15-0.57) nor in either of the subgroups (Asian: OR 0.84-1.04, p = 0.68-0.98; or non-Asian: OR 0.77-1.34, p = 0.33-0.93), in all genetic models. CONCLUSION: The PROGINS polymorphisms cannot be considered a risk factor for developing uterine leiomyoma.