title: Genetic variation in CYP19A1 and risk of breast cancer and fibrocystic breast conditions among women in Shanghai, China.
abstract: CYP19A1 encodes for aromatase, which irreversibly converts androgens to estrogens; variation in this gene may affect individual susceptibility to breast cancer and other sex hormone-dependent outcomes. In a case-control study nested within a breast self-examination trial conducted in China, we examined whether CYP19A1 polymorphisms (rs1870049, rs1004982, rs28566535, rs936306, rs11636639, rs767199, rs4775936, rs11575899, rs10046, and rs4646) were associated with risk of breast cancer and fibrocystic breast conditions. Cases were diagnosed with breast cancer (n = 614) or fibrocystic breast conditions (n = 465) during 1989 to 2000. Controls were free of breast disease during the same period (n = 879). Presence of proliferative changes within the extratumoral tissue of women with breast cancer and the lesions of women with fibrocystic conditions only was assessed. None of the polymorphisms were associated with overall risk of breast cancer or fibrocystic breast conditions. Differences in breast cancer risk, however, were observed by proliferation status. The risk of breast cancer with (but not without) proliferative fibrocystic conditions was increased among women homozygous for the minor allele of rs1004982 (C), rs28566535 (C), rs936306 (T), and rs4775936 (C) relative to those homozygous for the major allele [age-adjusted odds ratios (95% confidence intervals), 2.19 (1.24-3.85), 2.20 (1.27-3.82), 1.94 (1.13-3.30), and 1.95 (1.07-3.58), respectively]. Also, haplotypes inferred using all polymorphisms were not associated with overall risk of either outcome, although some block-specific haplotypes were associated with an increased risk of breast cancer with concurrent proliferative fibrocystic conditions. Our findings suggest that CYP19A1 variation may enhance breast cancer development in some women, but further confirmation is warranted.
authors.affiliation: Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Mailstop M5-C800, P.O. Box 19024, Seattle, WA 98109-1024, USA. cchen@fhcrc.org
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.forename: Lori C
authors.initials: LC
authors.lastname: Sakoda
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Doherty
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Loomis
authors.forename: Sherianne
authors.initials: S
authors.lastname: Fish
authors.forename: Roberta M
authors.initials: RM
authors.lastname: Ray
authors.forename: Ming Gang
authors.initials: MG
authors.lastname: Lin
authors.forename: Wenhong
authors.initials: W
authors.lastname: Fan
authors.forename: Lue Ping
authors.initials: LP
authors.lastname: Zhao
authors.forename: Dao Li
authors.initials: DL
authors.lastname: Gao
authors.forename: Helge
authors.initials: H
authors.lastname: Stalsberg
authors.forename: Ziding
authors.initials: Z
authors.lastname: Feng
authors.forename: David B
authors.initials: DB
authors.lastname: Thomas
mesh_terms: D000328:Adult; D000483:Alleles; D001141:Aromatase / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016504:Breast Self-Examination; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D005260:Female; D005348:Fibrocystic Breast Disease / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D001141:Aromatase