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American Journal of Epidemiology Advance Access originally published online on November 16, 2006
American Journal of Epidemiology 2007 165(3):235-245; doi:10.1093/aje/kwk015
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American Journal of Epidemiology Copyright © 2006 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.

Variants in Estrogen Biosynthesis Genes, Sex Steroid Hormone Levels, and Endometrial Cancer: A HuGE Review

Sara H. Olson1, Elisa V. Bandera2 and Irene Orlow1

1 Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY
2 Cancer Prevention and Control Program, Cancer Institute of New Jersey, New Brunswick, NJ

Correspondence to Dr. Sara H. Olson, Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 307 East 63 Street, New York, NY 10021 (e-mail: olsons{at}mskcc.org).

Variants in genes involved in estrogen biosynthesis are likely to be important in the etiology of endometrial cancer. This review summarizes data on variants in seven genes in the estrogen biosynthesis pathway and their relation to circulating levels of sex steroid hormones in women and to risk of endometrial cancer. Little or no association was found between genotypes of the cytochrome P-450 genes CYP11A1 (-528[TTTTA]n) or CYP17A1 (-34T/C) or the 17ß-hydroxysteroid dehydrogenase 1 gene HSD17B1 (Ser312Gly) and levels of progesterone, androgens, or estrogens. The position -34T/C variant in CYP17A1 appears to be associated with reduced risk of endometrial cancer, with those homozygous for the variant allele having about half the risk of those homozygous for the wild type. Linked variants in CYP19A1 (intron 4 [TTTA]n, intron 4 [TCT] insertion/deletion, exon 10 C/T) are related to some hormone levels and, based on two studies, to risk of endometrial cancer. For other genes (HSD3B1, HSD3B2, HSD17B2), no information is available on these associations. Results indicate the need to study other variants and haplotypes in these genes, particularly CYP17A1 and CYP19A1, as well as variants in other genes involved in hormone biosynthesis and metabolism pathways. Larger studies or combined studies that allow for investigation of gene-gene and gene-environment interactions are warranted.

androgens; CYP11A1; CYP17A1; CYP19A1; endometrial neoplasms; epidemiology; HSD3B; HSD17B

Abbreviations: CYP11A1, cytochrome P-450 11A1 gene; CYP17A1, cytochrome P-450 17A1 gene; CYP19A1, cytochrome P-450 19A1 gene; DHEA, dehydroepiandrosterone; DHEAS, dehydroepiandrosterone sulfate; HSD3B1, 3ß-hydroxysteroid dehydrogenase 1 gene; HSD3B2, 3ß-hydroxysteroid dehydrogenase 2 gene; HSD17B1, 17ß-hydroxysteroid dehydrogenase 1 gene; HSD17B2, 17ß-hydroxysteroid dehydrogenase 2 gene; SNP, single nucleotide polymorphism

Editor's note: This paper is also available on the website of the Human Genome Epidemiology Network (http://www.cdc.gov/genomics/hugenet/).


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