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A allele of SNP12 in estrogen receptor 1 was a risk factor for cryptorchidism in Asians: a systematic review with meta-analysis and trial sequential analysis

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Abstract

Objective

Some studies have been carried out to evaluate the association between SNP12 in estrogen receptor 1 and cryptorchidism, but the results remain inconsistent. We carried out a meta-analysis to explore the association between this polymorphism and cryptorchidism risk.

Methods

All eligible studies were searched in PubMed, Web of Science, Embase and Cochrane Library. Pooled odds ratios, with 95 % confidence intervals, were assessed for the association using fixed- and random-effects models.

Results

Overall, four case–control studies (363 cases, 415 controls) were included in the meta-analysis. No significant publication bias (P Begg = 0.308, P Egger = 0.288) was found. A allele of SNP12 in estrogen receptor 1 was protective factor to cryptorchidism in allele model, dominant genetic model and heterozygote comparison in Caucasians, but the result was turned out to be false positive by trial sequential analysis. However, A in allele model was risk factor to cryptorchidism in Asians (odds ratio 2.02, 95 % confidence interval 1.03–3.01, p = 0.946 for heterogeneity) and the result was turned out to be true positive by trial sequential analysis, even though there were merely two original studies.

Conclusions

The results of this meta-analysis suggest that A allele of SNP12 in estrogen receptor 1 may increase the risk of cryptorchidism in Asians. Meanwhile, further well-designed studies with large sample sizes are required to confirm the present findings, especially in Caucasians.

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References

  1. Hutson JM, Hasthorpe S, Heyns CF (1997) Anatomical and functional aspects of testicular descent and cryptorchidism. Endocr Rev 18:259–280

    CAS  PubMed  Google Scholar 

  2. Sijstermans K, Hack WW, Meijer RW, van der Voort-Doedens LM (2008) The frequency of undescended testis from birth to adulthood: a review. Int J Androl 31:1–11

    Article  CAS  PubMed  Google Scholar 

  3. Virtanen HE, Bjerknes R, Cortes D et al (2007) Cryptorchidism: classification, prevalence and long-term consequences. Acta Paediatr 96:611–616

    Article  PubMed  Google Scholar 

  4. Boisen KA, Kaleva M, Main KM et al (2004) Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries. Lancet 363:1264–1269

    Article  CAS  PubMed  Google Scholar 

  5. Boisen KA, Kaleva M, Main KM et al (2004) High and increasing prevalence of cryptorchidism in Denmark. Ugeskr Laeger 166:4372–4375

    PubMed  Google Scholar 

  6. Preiksa RT, Zilaitiene B, Matulevicius V et al (2005) Higher than expected prevalence of congenital cryptorchidism in Lithuania: a study of 1204 boys at birth and 1 year follow-up. Hum Reprod 20:1928–1932

    Article  CAS  PubMed  Google Scholar 

  7. Virtanen HE, Adamsson A (2012) Cryptorchidism and endocrine disrupting chemicals. Mol Cell Endocrinol 355:208–220

    Article  CAS  PubMed  Google Scholar 

  8. Svechnikov K, Stukenborg JB, Savchuck I, Söder O (2014) Similar causes of various reproductive disorders in early life. Asian J Androl 16:50–59

    Article  PubMed  Google Scholar 

  9. Vidaeff AC, Sever LE (2005) In utero exposure to environmental estrogens and male reproductive health: a systematic review of biological and epidemiologic evidence. Reprod Toxicol 20:5–20

    Article  CAS  PubMed  Google Scholar 

  10. Cederroth CR, Schaad O, Descombes P et al (2007) Estrogen receptor alpha is a major contributor to estrogen-mediated fetal testis dysgenesis and cryptorchidism. Endocrinology 148:5507–5519

    Article  CAS  PubMed  Google Scholar 

  11. Chevalier N, Brucker-Davis F, Lahlou N et al (2015) A negative correlation between insulin-like peptide 3 and bisphenol A in human cord blood suggests an effect of endocrine disruptors on testicular descent during fetal development. Hum Reprod 30:447–453

    Article  PubMed  Google Scholar 

  12. McLachlan JA (2001) Environmental signaling: what embryos and evolution teach us about endocrine disrupting chemicals. Endocr Rev 22:319–341

    Article  CAS  PubMed  Google Scholar 

  13. Mizuno K, Kojima Y, Kurokawa S, Kamisawa H, Kohri K, Hayashi Y (2011) Altered expression and localization of estrogen receptors alpha and beta in the testes of a cryptorchid rat model. Urology 77:251.e1–251.e6

    Article  Google Scholar 

  14. Kotula-Balak M, Gancarczyk M, Sadowska J, Bilinskai B (2005) The expression of aromatase, estrogen receptor alpha and estrogen receptor beta in mouse Leydig cells in vitro that derived from cryptorchid males. Eur J Histochem 49:59–62

    Article  CAS  PubMed  Google Scholar 

  15. Tremblay JJ, Robert NM, Laguë E (2009) Nuclear receptors, testosterone, and posttranslational modifications in human INSL3 promoter activity in testicular Leydig cells. Ann N Y Acad Sci 1160:205–212

    Article  CAS  PubMed  Google Scholar 

  16. Anand-Ivell R, Ivell R (2014) Insulin-like factor 3 as a monitor of endocrine disruption. Reproduction 147:R87–R95

    CAS  PubMed  Google Scholar 

  17. Yoshida R, Fukami M, Sasagawa I, Hasegawa T, Kamatani N, Ogata T (2005) Association of cryptorchidism with a specific haplotype of the estrogen receptor alpha gene: implication for the susceptibility to estrogenic environmental endocrine disruptors. J Clin Endocrinol Metab 90:4716–4721

    Article  CAS  PubMed  Google Scholar 

  18. Galan JJ, Guarducci E, Nuti F et al (2007) Molecular analysis of estrogen receptor alpha gene AGATA haplotype and SNP12 in European populations: potential protective effect for cryptorchidism and lack of association with male infertility. Hum Reprod 22:444–449

    Article  CAS  PubMed  Google Scholar 

  19. Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605

    Article  PubMed  Google Scholar 

  20. Wetterslev J, Thorlund K, Brok J, Gluud C (2009) Estimating required information size by quantifying diversity in random-effects model meta-analyses. BMC Med Res Methodol 9:86

    Article  PubMed  PubMed Central  Google Scholar 

  21. Borm GF, Donders AR (2009) Updating meta-analyses leads to larger type I errors than publication bias. J Clin Epidemiol 62:825–830

    Article  PubMed  Google Scholar 

  22. Brok J, Thorlund K, Gluud C, Wetterslev J (2008) Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses. J Clin Epidemiol 61:763–769

    Article  PubMed  Google Scholar 

  23. Tang KF, Zheng JZ, **ng JP (2011) Molecular analysis of SNP12 in estrogen receptor α gene in hypospadiac or cryptorchid patients from Northwestern China. Urol Int 87:359–362

    Article  CAS  PubMed  Google Scholar 

  24. Wang Y, Barthold J, Figueroa E et al (2008) Analysis of five single nucleotide polymorphisms in the ESR1 gene in cryptorchidism. Birth Defects Res A Clin Mol Teratol 82:482–485

    Article  CAS  PubMed  Google Scholar 

  25. Nef S, Shipman T, Parada LF (2000) A molecular basis for estrogen-induced cryptorchidism. Dev Biol 224:354–361

    Article  CAS  PubMed  Google Scholar 

  26. Emmen JM, McLuskey A, Adham IM et al (2000) Involvement of insulin-like factor 3 (Insl3) in diethylstilbestrol-induced cryptorchidism. Endocrinology 141:846–849

    Article  CAS  PubMed  Google Scholar 

  27. Bay K, Main KM, Toppari J, Skakkebæk NE (2011) Testicular descent: INSL3, testosterone, genes and the intrauterine milieu. Nat Rev Urol 8:187–196

    Article  CAS  PubMed  Google Scholar 

  28. Wetterslev J, Thorlund K, Brok J, Gluud C (2008) Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis. J Clin Epidemiol 61:64–75

    Article  PubMed  Google Scholar 

  29. Higgins JP, Whitehead A, Simmonds M (2011) Sequential methods for random-effects meta-analysis. Stat Med 30:903–921

    Article  PubMed  Google Scholar 

  30. Kulinskaya E, Wood J (2014) Trial sequential methods for meta-analysis. Res Synth Methods 5:212–220

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Children’s Hospital of Chongqing Medical University Clinical Research Projects (Project No: lcyj2014-16).

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    Authors and Affiliations

    1. Department of Pediatric Surgery, Chengdu Women’s and Children’s Central Hospital, Chengdu, China

      Changkai Deng

    2. Department of Urology Surgery, Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorder, Key Laboratory of Pediatrics in Chongqing (CSTC2009CA5002), Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, No.136, Zhongshan 2 RD, Yuzhong District, Chongqing, 400014, China

      Changkai Deng, Xuliang Li & Feng Liu

    3. Chengdu Center for Disease Control and Prevention, Chengdu, China

      Rong Dai

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    1. Changkai Deng
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    Correspondence to Feng Liu.

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    Changkai Deng and Rong Dai contributed equally to this work.

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    Deng, C., Dai, R., Li, X. et al. A allele of SNP12 in estrogen receptor 1 was a risk factor for cryptorchidism in Asians: a systematic review with meta-analysis and trial sequential analysis. Pediatr Surg Int 32, 981–987 (2016). https://doi.org/10.1007/s00383-016-3926-x

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    • DOI: https://doi.org/10.1007/s00383-016-3926-x

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