title: Associations between CYP19A1 polymorphisms, Native American ancestry, and breast cancer risk and mortality: the Breast Cancer Health Disparities Study.
abstract: The cytochrome p450 family 19 gene (CYP19A1) encodes for aromatase, which catalyzes the final step in estrogen biosynthesis and conversion of androgens to estrogens. Genetic variation in CYP19A1 is linked to higher circulating estrogen levels and increased aromatase expression. Using data from the Breast Cancer Health Disparities Study, a consortium of three population-based case-control studies in the United States (n = 3,030 non-Hispanic Whites; n = 2,893 Hispanic/Native Americans (H/NA) and Mexico (n = 1,810), we examined influence of 25 CYP19A1 tagging single-nucleotide polymorphisms (SNPs) on breast cancer risk and mortality, considering NA ancestry. Odds ratios (ORs) and 95 % confidence intervals (CIs) and hazard ratios estimated breast cancer risk and mortality. After multiple comparison adjustment, none of the SNPs were significantly associated with breast cancer risk or mortality. Two SNPs remained significantly associated with increased breast cancer risk in women of moderate to high NA ancestry (≥29 %): rs700518, ORGG 1.36, 95 % CI 1.11-1.67 and rs11856927, ORGG 1.35, 95 % CI 1.05-1.72. A significant interaction was observed for rs2470144 and menopausal status (p adj = 0.03); risk was increased in postmenopausal (ORAA 1.22, 95 % CI 1.05-1.14), but not premenopausal (ORAA 0.78, 95 % CI 0.64-0.95) women. The absence of an overall association with CYP19A1 and breast cancer risk is similar to previous literature. However, this analysis provides support that variation in CYP19A1 may influence breast cancer risk differently in women with moderate to high NA ancestry. Additional research is warranted to investigate the how variation in an estrogen-regulating gene contributes to racial/ethnic disparities in breast cancer.
authors.affiliation: Department of Epidemiology and Population Health, James Graham Brown Cancer Center, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray St., Louisville, KY, 40202, USA, stephanie.boone@louisville.edu.
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Boone
authors.forename: Kathy B
authors.initials: KB
authors.lastname: Baumgartner
authors.forename: Richard N
authors.initials: RN
authors.lastname: Baumgartner
authors.forename: Avonne E
authors.initials: AE
authors.lastname: Connor
authors.forename: Christina M
authors.initials: CM
authors.lastname: Pinkston
authors.forename: Shesh N
authors.initials: SN
authors.lastname: Rai
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Riley
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Hines
authors.forename: Anna R
authors.initials: AR
authors.lastname: Giuliano
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Stern
authors.forename: Gabriela
authors.initials: G
authors.lastname: Torres-Mejía
authors.forename: Roger K
authors.initials: RK
authors.lastname: Wolff
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
mesh_terms: D000328:Adult; D000368:Aged; D001141:Aromatase / Q000235:genetics*; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D001141:Aromatase; C561410:CYP19A1 protein, human
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