title: Estrogen-related genes and their contribution to racial differences in breast cancer risk.
abstract: Racial differences in breast cancer risk, including the risks of hormone receptor subtypes of breast cancer, have been previously reported. We evaluated whether variation in genes related to estrogen metabolism (COMT, CYP1A1, CYP1B1, CYP17A1, CYP19A1, ESR1, GSTM1, GSTP1, GSTT1, HSD17B1, SULT1A1, and UGT1A1) contributes to breast cancer risk and/or racial differences in risk within the CARE study, a multi-centered, population-based case-control study of breast cancer. Genetic variation was assessed as single nucleotide polymorphisms (SNPs), haplotypes, and SNP-hormone therapy (HT) interactions within a subset of 1,644 cases and 1,451 controls, including 949 Black women (493 cases and 456 controls), sampled from the CARE study population. No appreciable associations with breast cancer risk were detected for single SNPs or haplotypes in women overall. We detected SNP-HT interactions in women overall within CYP1B1 (rs1800440; p                         (het) = 0.003) and within CYP17A1 (rs743572; p                         (het) = 0.009) in which never users of HT were at a decreased risk of breast cancer, while ever users were at a non-significant increased risk. When investigated among racial groups, we detected evidence of an SNP-HT interaction with CYP1B1 in White women (p value = 0.02) and with CYP17A1 in Black women (p value = 0.04). This analysis suggests that HT use may modify the effect of variation in estrogen-related genes on breast cancer risk, which may affect Black and White women to a different extent.
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. kreding@u.washington.edu
authors.forename: Kerryn W
authors.initials: KW
authors.lastname: Reding
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.forename: Kimberly
authors.initials: K
authors.lastname: Lowe
authors.forename: David R
authors.initials: DR
authors.lastname: Doody
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Carlson
authors.forename: Christina T
authors.initials: CT
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Houck
authors.forename: Linda K
authors.initials: LK
authors.lastname: Weiss
authors.forename: Polly A
authors.initials: PA
authors.lastname: Marchbanks
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Robert
authors.initials: R
authors.lastname: Spirtas
authors.forename: Jill A
authors.initials: JA
authors.lastname: McDonald
authors.forename: Brian L
authors.initials: BL
authors.lastname: Strom
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Burkman
authors.forename: Michael S
authors.initials: MS
authors.lastname: Simon
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Liff
authors.forename: Janet R
authors.initials: JR
authors.lastname: Daling
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Malone
mesh_terms: D000328:Adult; D000368:Aged; D044383:Black People; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism*; D016022:Case-Control Studies; D004967:Estrogens / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People
chemical_list: D004967:Estrogens