title: Associations between the CYP17, CYPIB1, COMT and SHBG polymorphisms and serum sex hormones in post-menopausal breast cancer survivors.
abstract: Several polymorphisms have been identified in genes that code for enzymes involved with estrogen biosynthesis and metabolism. Little is known about the functional relevance of these polymorphisms on sex hormones in vivo. We examined the association between CYP17, CYP1B1, COMT or SHBG genotypes and serum concentrations of estrone, estradiol, free estradiol, sex hormone-binding globulin (SHBG), testosterone, free testosterone and dehyroepiandrosterone in 366 post-menopausal breast cancer survivors in New Mexico, California and Washington. Hormone levels were determined by high performance liquid chromatography and radioimmunoassay in blood drawn approximately 2 years post-diagnosis. We used generalized linear regression to calculate mean hormone levels by genotype, adjusting for age, race/ethnicity, stage, study site, tamoxifen use, number of remaining ovaries, hormone therapy use, marital status and BMI. No associations were observed between any of the genotypes and sex hormones when analyzing the main effects. In subgroup analyses, androgen levels of Hispanic women with the variant (A2) CYP17 genotype were 46-87% higher than those of women with the wild-type; androgen levels were 13-20% lower in non-Hispanic whites with the variant genotype; no difference by genotype was observed for African-American women. Current tamoxifen users with the variant asn(327) SHBG genotype had 81% higher serum SHBG and 39% lower free testosterone concentrations than women with the wild-type genotype. Non-tamoxifen users with the variant SHBG allele had elevated free estradiol levels. These results provide little evidence that the CYP17, CYP1B1, and COMT polymorphisms are associated with different sex hormone levels in post-menopausal breast cancer survivors.
authors.affiliation: Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M4-B402, Seattle, WA, 98109-1024, USA.
authors.forename: Page E
authors.initials: PE
authors.lastname: Abrahamson
authors.forename: Shelley S
authors.initials: SS
authors.lastname: Tworoger
authors.forename: Erin J
authors.initials: EJ
authors.lastname: Aiello
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Ulrich
authors.forename: Frank D
authors.initials: FD
authors.lastname: Gilliland
authors.forename: Frank Z
authors.initials: FZ
authors.lastname: Stanczyk
authors.forename: Richard
authors.initials: R
authors.lastname: Baumgartner
authors.forename: Kathy
authors.initials: K
authors.lastname: Baumgartner
authors.forename: Bess
authors.initials: B
authors.lastname: Sorensen
authors.forename: Rachel
authors.initials: R
authors.lastname: Ballard-Barbash
authors.forename: Anne
authors.initials: A
authors.lastname: McTiernan
mesh_terms: D000293:Adolescent; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D003687:Dehydroepiandrosterone / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017698:Postmenopause; D011863:Radioimmunoassay / Q000379:methods; D012738:Sex Hormone-Binding Globulin / Q000235:genetics*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*; D013739:Testosterone / Q000378:metabolism
chemical_list: D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D003687:Dehydroepiandrosterone; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D013254:Steroid 17-alpha-Hydroxylase