title: Polymorphisms in steroid hormone biosynthesis genes and risk of breast cancer and fibrocystic breast conditions in Chinese women.
abstract: Common variants in genes encoding for key enzymes involved in steroidogenesis may alter sex steroid hormone levels, thereby influencing susceptibility to breast carcinoma and related conditions. In a case-control study of Chinese women, we examined genotypes of the CYP11A1 pentanucleotide [(TAAAA)n] repeat (D15S520), CYP17A1 rs743572, and HSD17B1 rs605059 polymorphisms in relation to the risk of breast cancer and fibrocystic breast conditions, comparing 615 women with breast cancer and 467 women with fibrocystic breast conditions separately with 879 women without clinical breast disease. We also evaluated whether these relationships differed by the presence of proliferation in the extratumoral epithelium or fibrocystic lesions, menopausal status, or body mass index. Only CYP11A1 genotype was related to breast cancer risk, with women homozygous for the 4-repeat allele, relative to those homozygous for the 6-repeat allele, at reduced risk (age-adjusted odds ratio, 0.58; 95% confidence interval, 0.37-0.91). There was some suggestion of a stronger inverse association for breast cancer with evidence of proliferation in the extratumoral epithelium than for breast cancer without extratumoral proliferation. Breast cancer risk associated with CYP11A1 genotype did not differ by menopausal status or body mass index level. No associations between CYP11A1, CYP17A1, and HSD17B1 genotypes and risk of fibrocystic breast conditions were observed. Our findings support the possibility that common allelic variation at the CYP11A1 D15S520 locus alters breast cancer risk in Chinese women.
authors.affiliation: Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
authors.forename: Lori C
authors.initials: LC
authors.lastname: Sakoda
authors.forename: Christie
authors.initials: C
authors.lastname: Blackston
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Doherty
authors.forename: Roberta M
authors.initials: RM
authors.lastname: Ray
authors.forename: Ming Gang
authors.initials: MG
authors.lastname: Lin
authors.forename: Helge
authors.initials: H
authors.lastname: Stalsberg
authors.forename: Dao Li
authors.initials: DL
authors.lastname: Gao
authors.forename: Ziding
authors.initials: Z
authors.lastname: Feng
authors.forename: David B
authors.initials: DB
authors.lastname: Thomas
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics*; D004960:Estradiol Dehydrogenases / Q000235:genetics*; D005260:Female; D005348:Fibrocystic Breast Disease / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
chemical_list: D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme