title: Variants of estrogen-related genes and breast cancer risk in European and African American women.
abstract: It has been observed previously that compared with women of European ancestry (EA), those of African ancestry (AA) are more likely to develop estrogen receptor (ER)-negative breast cancer, although the mechanisms have not been elucidated. We tested the associations between breast cancer risk and a targeted set of 20 genes known to be involved in estrogen synthesis, metabolism, and response and potential gene-environment interactions using data and samples from 1307 EA (658 cases) and 1365 AA (621 cases) participants from the Women's Circle of Health Study (WCHS). Multivariable logistic regression found evidence of associations with single-nucleotide polymorphisms (SNPs) in the ESR1 gene in EA women (rs1801132, odds ratio (OR)=1.47, 95% CI=1.20-1.80, P=0.0002; rs2046210, OR=1.24, 95% CI=1.04-1.47, P=0.02; and rs3020314, OR=1.43, 95% CI=1.19-1.70, P=0.00009), but not in AA women. The only other gene associated with breast cancer risk was CYP1A2 in AA women (rs2470893, OR=1.42, 95% CI=1.00-2.02, P=0.05), but not in EA women. When stratified by ER status, ESR1 rs1801132, rs2046210, and rs3020314 showed stronger associations in ER-positive than in ER-negative breast cancer in only EA women. Associations with the ESR1 SNPs in EA women also appeared to be stronger with longer endogenous estrogen exposure or hormonal replacement therapy use. Our results indicate that there may be differential genetic influences on breast cancer risk in EA compared with AA women and that these differences may be modified by tumor subtype and estrogen exposures. Future studies with a larger sample size may determine the full contribution of estrogen-related genes to racial/ethnic differences in breast cancer.
authors.affiliation: Roswell Park Cancer InstituteElm and Carlton Streets, Buffalo, New York 14263, USAUniversity of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania, USAIcahn School of Medicine at Mount SinaiNew York, New York, USANew Jersey Department of HealthTrenton, New Jersey, USARutgers Cancer Institute of New JerseyNew Brunswick, New Jersey, USA Roswell Park Cancer InstituteElm and Carlton Streets, Buffalo, New York 14263, USAUniversity of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania, USAIcahn School of Medicine at Mount SinaiNew York, New York, USANew Jersey Department of HealthTrenton, New Jersey, USARutgers Cancer Institute of New JerseyNew Brunswick, New Jersey, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Quan
authors.affiliation: Roswell Park Cancer InstituteElm and Carlton Streets, Buffalo, New York 14263, USAUniversity of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania, USAIcahn School of Medicine at Mount SinaiNew York, New York, USANew Jersey Department of HealthTrenton, New Jersey, USARutgers Cancer Institute of New JerseyNew Brunswick, New Jersey, USA.
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Hong
authors.affiliation: Roswell Park Cancer InstituteElm and Carlton Streets, Buffalo, New York 14263, USAUniversity of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania, USAIcahn School of Medicine at Mount SinaiNew York, New York, USANew Jersey Department of HealthTrenton, New Jersey, USARutgers Cancer Institute of New JerseyNew Brunswick, New Jersey, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Zirpoli
authors.affiliation: Roswell Park Cancer InstituteElm and Carlton Streets, Buffalo, New York 14263, USAUniversity of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania, USAIcahn School of Medicine at Mount SinaiNew York, New York, USANew Jersey Department of HealthTrenton, New Jersey, USARutgers Cancer Institute of New JerseyNew Brunswick, New Jersey, USA.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Roberts
authors.affiliation: Roswell Park Cancer InstituteElm and Carlton Streets, Buffalo, New York 14263, USAUniversity of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania, USAIcahn School of Medicine at Mount SinaiNew York, New York, USANew Jersey Department of HealthTrenton, New Jersey, USARutgers Cancer Institute of New JerseyNew Brunswick, New Jersey, USA.
authors.forename: Thaer
authors.initials: T
authors.lastname: Khoury
authors.affiliation: Roswell Park Cancer InstituteElm and Carlton Streets, Buffalo, New York 14263, USAUniversity of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania, USAIcahn School of Medicine at Mount SinaiNew York, New York, USANew Jersey Department of HealthTrenton, New Jersey, USARutgers Cancer Institute of New JerseyNew Brunswick, New Jersey, USA.
authors.forename: Lara E
authors.initials: LE
authors.lastname: Sucheston-Campbell
authors.affiliation: Roswell Park Cancer InstituteElm and Carlton Streets, Buffalo, New York 14263, USAUniversity of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania, USAIcahn School of Medicine at Mount SinaiNew York, New York, USANew Jersey Department of HealthTrenton, New Jersey, USARutgers Cancer Institute of New JerseyNew Brunswick, New Jersey, USA.
authors.forename: Dana H
authors.initials: DH
authors.lastname: Bovbjerg
authors.affiliation: Roswell Park Cancer InstituteElm and Carlton Streets, Buffalo, New York 14263, USAUniversity of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania, USAIcahn School of Medicine at Mount SinaiNew York, New York, USANew Jersey Department of HealthTrenton, New Jersey, USARutgers Cancer Institute of New JerseyNew Brunswick, New Jersey, USA.
authors.forename: Lina
authors.initials: L
authors.lastname: Jandorf
authors.affiliation: Roswell Park Cancer InstituteElm and Carlton Streets, Buffalo, New York 14263, USAUniversity of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania, USAIcahn School of Medicine at Mount SinaiNew York, New York, USANew Jersey Department of HealthTrenton, New Jersey, USARutgers Cancer Institute of New JerseyNew Brunswick, New Jersey, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Pawlish
authors.affiliation: Roswell Park Cancer InstituteElm and Carlton Streets, Buffalo, New York 14263, USAUniversity of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania, USAIcahn School of Medicine at Mount SinaiNew York, New York, USANew Jersey Department of HealthTrenton, New Jersey, USARutgers Cancer Institute of New JerseyNew Brunswick, New Jersey, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Ciupak
authors.affiliation: Roswell Park Cancer InstituteElm and Carlton Streets, Buffalo, New York 14263, USAUniversity of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania, USAIcahn School of Medicine at Mount SinaiNew York, New York, USANew Jersey Department of HealthTrenton, New Jersey, USARutgers Cancer Institute of New JerseyNew Brunswick, New Jersey, USA.
authors.forename: Warren
authors.initials: W
authors.lastname: Davis
authors.affiliation: Roswell Park Cancer InstituteElm and Carlton Streets, Buffalo, New York 14263, USAUniversity of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania, USAIcahn School of Medicine at Mount SinaiNew York, New York, USANew Jersey Department of HealthTrenton, New Jersey, USARutgers Cancer Institute of New JerseyNew Brunswick, New Jersey, USA.
authors.forename: Elisa V
authors.initials: EV
authors.lastname: Bandera
authors.affiliation: Roswell Park Cancer InstituteElm and Carlton Streets, Buffalo, New York 14263, USAUniversity of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania, USAIcahn School of Medicine at Mount SinaiNew York, New York, USANew Jersey Department of HealthTrenton, New Jersey, USARutgers Cancer Institute of New JerseyNew Brunswick, New Jersey, USA.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
authors.affiliation: Roswell Park Cancer InstituteElm and Carlton Streets, Buffalo, New York 14263, USAUniversity of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania, USAIcahn School of Medicine at Mount SinaiNew York, New York, USANew Jersey Department of HealthTrenton, New Jersey, USARutgers Cancer Institute of New JerseyNew Brunswick, New Jersey, USA song.yao@roswellpark.org.
authors.forename: Song
authors.initials: S
authors.lastname: Yao
mesh_terms: D001741:Black or African American / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000235:genetics*; D011980:Receptors, Progesterone / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics*
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D019388:Cytochrome P-450 CYP1A2
keywords: African–American; ESR1; breast cancer; disparity; estrogen metabolism; estrogen receptor; estrogen response; estrogen synthesis