title: Polymorphisms in genes of the steroid hormone biosynthesis and metabolism pathways and endometrial cancer risk.
abstract: OBJECTIVE
  The incidence of endometrial cancer has recently increased substantially and studies have shown that altered levels of exogenous and endogenous hormones are associated with individual variation in endometrial cancer risk. The environmental and reproductive risk factors that influence these hormones are well known, however, genetic variants involved in hormone biosynthesis and estrogen metabolism have not been well established in endometrial cancer.
  
  
  METHODS
  To determine whether polymorphisms in genes of the steroid hormone biosynthesis and metabolism pathways are associated with endometrial cancer risk, 28 polymorphisms in 18 genes were genotyped in 191 endometrial cancer cases and 291 healthy controls.
  
  
  RESULTS
  The GSTM1 deletion and the variant (GG) genotype of the CYP1B1 rs1800440 polymorphism were associated with a decreased risk of developing endometrial cancer. Furthermore, combinations of haplotypes in CYP1A1, CYP1B1 and GSTs were associated with a decreased risk. The analysis of the repeat polymorphisms revealed that women with the long repeat allele length of the ESR1 (GT)n repeat polymorphism were at an increased risk of developing endometrial cancer. Conversely, women with two long repeat length alleles of the (CAG)n repeat polymorphism in the AR correlated with a decrease in endometrial cancer risk compared to women with one or two alleles with the short repeat length.
  
  
  CONCLUSIONS
  The findings are consistent with our hypothesis that variability in genes involved in steroidogenesis and estrogen metabolism may alter the risk of developing endometrial cancer, suggesting that they may be useful as biomarkers for genetic susceptibility to endometrial cancer.
authors.affiliation: Discipline of Medical Genetics, School of Biomedical Sciences, Faculty of Health, University of Newcastle, Australia.
authors.forename: Katie A
authors.initials: KA
authors.lastname: Ashton
authors.forename: Anthony
authors.initials: A
authors.lastname: Proietto
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Otton
authors.forename: Ian
authors.initials: I
authors.lastname: Symonds
authors.forename: Mark
authors.initials: M
authors.lastname: McEvoy
authors.forename: John
authors.initials: J
authors.lastname: Attia
authors.forename: Michael
authors.initials: M
authors.lastname: Gilbert
authors.forename: Ute
authors.initials: U
authors.lastname: Hamann
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D053898:Biosynthetic Pathways / Q000235:genetics; D016889:Endometrial Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004960:Estradiol Dehydrogenases / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011944:Receptors, Androgen / Q000235:genetics; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D012739:Gonadal Steroid Hormones; D047908:Intracellular Signaling Peptides and Proteins; C439067:MRFAP1 protein, human; D009687:Nuclear Proteins; D011944:Receptors, Androgen; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human; D001189:Aryl Hydrocarbon Hydroxylases; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase