Genetic variations in MicroRNA genes and cancer risk: A field synopsis and meta-analysis

TY - JOUR

T1 - Genetic variations in MicroRNA genes and cancer risk

T2 - A field synopsis and meta-analysis

AU - Park, Jae Hyon

AU - Jeong, Gwang Hun

AU - Lee, Kwang Seob

AU - Lee, Keum Hwa

AU - Suh, Jin-Soon

AU - Eisenhut, Michael

AU - van der Vliet, Hans J

AU - Kronbichler, Andreas

AU - Stubbs, Brendon

AU - Solmi, Marco

AU - Dragioti, Elena

AU - Koyanagi, Ai

AU - Shin, Jae Il

AU - Gamerith, Gabriele

N1 - © 2020 Stichting European Society for Clinical Investigation Journal Foundation.

PY - 2020/4/1

Y1 - 2020/4/1

N2 - Background: Cancer risk has been associated with certain gene variations in microRNA (miRNA), but conflicting evidence warrants re-assessing of significant results in meta-analyses. We summarized published meta-analyses that assess the associations between miRNA polymorphism and cancers to show the validity of the findings. Method: We searched PubMed and investigated the results of meta-analyses published through November 2018. We re-assessed the results based on false-positive report probability (FPRP) to test the noteworthiness of the associations. Results: Sixty-eight miRNA polymorphisms in 45 meta-analyses associated with cancer were included. Four (7.4%) and sixteen (25.0%) single nucleotide polymorphisms (SNPs) were noteworthy (FPRP < 0.2) at a prior probability of 0.001 for interesting candidate genes and a statistical power to detect an odds ratio (OR) of 1.1 and 1.5, respectively. The four miRNA SNPs noteworthy at an OR of 1.1 were as follows: miR-146a/rs2910164 Cvs.G; miR-27a/rs895819 Cvs.T; miR-423/rs6505162 Cvs.A; and miR-605/rs2043556 Cvs.T. The 16 SNPs noteworthy at an OR of 1.5 include the four genotype comparisons at an OR of 1.1, and the additional 12 genotype comparisons were as follows: miR-196a2/rs11614913 Tvs.C; miR-27a/rs895819 GGvs.AA + AG; miR-196a2/rs11614913 C vs.T; miR-146a/rs2910164 Gvs.C; miR-196a2/rs11614913 Tvs.C; miR-146a/rs2910164 Cvs.G; miR-499/rs3746444 homozygous model; miR-146a/rs2910164 CCvs.GG + GC; miR-499/rs3746444 TCvs.TT; miR-499/rs3746444 GAvs.AA; miR-146a/rs2910164 CCvs.GG; and miR-499/rs3746444 Gvs.A. No association was noteworthy at a prior probability of 0.000001. Conclusion: Out of 68 published associations of miRNA polymorphisms with cancer, sixteen have shown noteworthiness in our re-assessing meta-analysis. Our findings summarize the results of meta-analyses on the association of cancer with SNPs and underline the importance of interpreting results with caution.

AB - Background: Cancer risk has been associated with certain gene variations in microRNA (miRNA), but conflicting evidence warrants re-assessing of significant results in meta-analyses. We summarized published meta-analyses that assess the associations between miRNA polymorphism and cancers to show the validity of the findings. Method: We searched PubMed and investigated the results of meta-analyses published through November 2018. We re-assessed the results based on false-positive report probability (FPRP) to test the noteworthiness of the associations. Results: Sixty-eight miRNA polymorphisms in 45 meta-analyses associated with cancer were included. Four (7.4%) and sixteen (25.0%) single nucleotide polymorphisms (SNPs) were noteworthy (FPRP < 0.2) at a prior probability of 0.001 for interesting candidate genes and a statistical power to detect an odds ratio (OR) of 1.1 and 1.5, respectively. The four miRNA SNPs noteworthy at an OR of 1.1 were as follows: miR-146a/rs2910164 Cvs.G; miR-27a/rs895819 Cvs.T; miR-423/rs6505162 Cvs.A; and miR-605/rs2043556 Cvs.T. The 16 SNPs noteworthy at an OR of 1.5 include the four genotype comparisons at an OR of 1.1, and the additional 12 genotype comparisons were as follows: miR-196a2/rs11614913 Tvs.C; miR-27a/rs895819 GGvs.AA + AG; miR-196a2/rs11614913 C vs.T; miR-146a/rs2910164 Gvs.C; miR-196a2/rs11614913 Tvs.C; miR-146a/rs2910164 Cvs.G; miR-499/rs3746444 homozygous model; miR-146a/rs2910164 CCvs.GG + GC; miR-499/rs3746444 TCvs.TT; miR-499/rs3746444 GAvs.AA; miR-146a/rs2910164 CCvs.GG; and miR-499/rs3746444 Gvs.A. No association was noteworthy at a prior probability of 0.000001. Conclusion: Out of 68 published associations of miRNA polymorphisms with cancer, sixteen have shown noteworthiness in our re-assessing meta-analysis. Our findings summarize the results of meta-analyses on the association of cancer with SNPs and underline the importance of interpreting results with caution.

KW - FPRP

KW - cancer

KW - gene variant

KW - meta-analysis

KW - microRNA

UR - http://www.scopus.com/inward/record.url?scp=85081233239&partnerID=8YFLogxK

U2 - 10.1111/eci.13203

DO - 10.1111/eci.13203

M3 - Review article

C2 - 31984489

SN - 0014-2972

VL - 50

SP - e13203

JO - European Journal of Clinical Investigation

JF - European Journal of Clinical Investigation

IS - 4

M1 - e13203

ER -