Environmental and genetic contributors to hypospadias: A review of the epidemiologic evidence
Article first published online: 8 JUN 2012
Copyright © 2012 Wiley Periodicals, Inc.
Birth Defects Research Part A: Clinical and Molecular Teratology
Volume 94, Issue 7, pages 499–510, July 2012
How to Cite
Carmichael, S. L., Shaw, G. M. and Lammer, E. J. (2012), Environmental and genetic contributors to hypospadias: A review of the epidemiologic evidence. Birth Defects Research Part A: Clinical and Molecular Teratology, 94: 499–510. doi: 10.1002/bdra.23021
- Issue published online: 9 JUL 2012
- Article first published online: 8 JUN 2012
- Manuscript Accepted: 28 MAR 2012
- Manuscript Revised: 22 MAR 2012
- Manuscript Received: 31 JAN 2012
- National Institutes of Health. Grant Number: R01ES017060
- Centers for Disease Control and Prevention. Grant Number: 6U01DD000489
This review evaluates current knowledge related to trends in the prevalence of hypospadias, the association of hypospadias with endocrine-disrupting exposures, and the potential contribution of genetic susceptibility to its etiology. The review focuses on epidemiologic evidence. Increasing prevalence of hypospadias has been observed, but such increases tend to be localized to specific regions or time periods. Thus, generalized statements that hypospadias is increasing are unsupported. Owing to the limitations of study designs and inconsistent results, firm conclusions cannot be made regarding the association of endocrine-disrupting exposures with hypospadias. Studies with more rigorous study designs (e.g., larger and more detailed phenotypes) and exposure assessment that encompasses more breadth and depth (e.g., specific endocrine-related chemicals) will be critical to make better inferences about these important environmental exposures. Many candidate genes for hypospadias have been identified, but few of them have been examined to an extent that enables solid conclusions. Further study is needed that includes larger sample sizes, comparison groups that are more representative of the populations from which the cases were derived, phenotype-specific analyses, and more extensive exploration of variants. In conclusion, examining the associations of environmental and genetic factors with hypospadias remain important areas of inquiry, although our actual understanding of their contribution to hypospadias risk in humans is currently limited. Birth Defects Research (Part A) 2012. © 2012 Wiley Periodicals, Inc.