title: Variants in estrogen biosynthesis genes, sex steroid hormone levels, and endometrial cancer: a HuGE review.
abstract: 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 17beta-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.
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. olsons@mskcc.org
authors.forename: Sara H
authors.initials: SH
authors.lastname: Olson
authors.forename: Elisa V
authors.initials: EV
authors.lastname: Bandera
authors.forename: Irene
authors.initials: I
authors.lastname: Orlow
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D000728:Androgens / Q000096:biosynthesis / Q000097:blood; D001141:Aromatase / Q000235:genetics; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D016889:Endometrial Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D004960:Estradiol Dehydrogenases / Q000235:genetics; D004967:Estrogens / Q000096:biosynthesis* / Q000097:blood; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis* / Q000097:blood; D006801:Humans; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011374:Progesterone / Q000096:biosynthesis / Q000097:blood; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics
chemical_list: D000728:Androgens; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D011374:Progesterone; D003577:Cytochrome P-450 Enzyme System; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human; D001141:Aromatase; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme