http://orcid.org/0000-0003-2069-5535
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Abstract
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.
| Abbreviations | ||
| A | = | number of unduplicated articles that contributed to instability |
| AM | = | analysis model |
| B | = | number of robust comparisons |
| BC | = | breast cancer |
| BLC | = | bladder cancer |
| cDNA | = | complementary deoxyribonucleic acid |
| CI | = | confidence interval |
| CID | = | confidence interval difference |
| CRC | = | colorectal cancer |
| D | = | decreased risk |
| EH | = | eliminated heterogeneity |
| F | = | fixed-effects |
| FDR | = | False Discovery Rate |
| GUC | = | genitourinary cancers |
| GS | = | gained significance |
| HB | = | hospital-based |
| HWE | = | Hardy–Weinberg Equilibrium |
| I | = | increased risk |
| I2 | = | measure of heterogeneity |
| kDa | = | kiloDalton |
| LAC | = | laryngeal cancer |
| LUC | = | lung cancer |
| maf | = | minor allele frequency |
| n | = | number of studies |
| N | = | number of comparisons |
| NM | = | not mentioned |
| NOS | = | Newcastle-Ottawa Scale |
| OR | = | odds ratio |
| Pa | = | P value for association |
| Paδ | = | P value for association (pre-FDR) |
| PaF | = | P value for association FDR-corrected |
| Pb | = | P value for heterogeneity |
| PB | = | population-based |
| PC | = | prostate cancer |
| PRISMA | = | Preferred Reporting Items for Systematic Reviews and Meta-Analyses |
| PRO | = | pre-outlier |
| PSO | = | post-outlier |
| R | = | random-effects |
| [R] | = | reference |
| RC | = | respiratory cancers |
| RNS | = | retained non-significance |
| ROS | = | reactive oxygen species |
| SEP | = | selenoproteins |
| SEP15 | = | selenoprotein gene |
| SNP | = | single nucleotide polymorphism |
| SW | = | Shapiro-Wilk test |
| USA | = | United States of America |
| vv | = | variant |
| wv | = | heterozygous |
| ww | = | wild-type |
Availability of data and material
Data and related materials are supplied as supplementary files.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Additional information
Notes on contributors
Noel Pabalan
Noel Pabalan and Phuntila Tharabenjasin contributed in content and study design conception; Noel Pabalan and Phuntila Tharabenjasin wrote the initial, subsequent, and final drafts; Data extraction and analysis were done by Noel Pabalan, Phuntila Tharabenjasin, and Hamdi Jarjanazi. Review of the initial and final drafts was done by Sitakan Natphopsuk and Niramai Ekaratcharoenchai.